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Honours Projects School of Science and Health 3610 Bachelor of Medical Science (Honours) 3611 Bachelor of Science (Honours) 4657 Bachelor of Health Science (Honours) 2014
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Honours Projects

School of Science and Health

3610 Bachelor of Medical Science (Honours)

3611 Bachelor of Science (Honours)

4657 Bachelor of Health Science (Honours)

2014

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Dear potential Honours student, Congratulations on your great success so far in your undergraduate studies! You have been selected to receive this information amongst only a few students who may qualify to continue their studies by undertaking an Honours project in Medical Science, Science or Health Science. This booklet will list available projects for the intake at the beginning of 2014 in the School of Science and Health. Please note that the projects listed may be on Campbelltown, Hawkesbury, Penrith, Parramatta campus or at external facilities. Further, some of the project areas listed will allow more than one Honours project. After you have browsed through the booklet and if you are interested in starting Honours, here is what you need to do next:

1. Attend the Honours information luncheons for which you will have received an invitation. At the luncheon you will receive more information about the Honours program and the application process. The luncheons will be a great opportunity to meet supervisors and current Honours students.

2. After the luncheon, or if you were unable to attend, please contact the supervisors listed

in the booklet where you might be interested to undertake your Honours studies in (note that it is a good idea to keep your options open and have at least 3-4 choices as depending on demand not every student may get their first choice of projects); make and appointment with those supervisors and ask them all you need to know about the project.

3. Fill in the application on line by 31st January 2014 at the following link:

https://applyonline.uws.edu.au/connect/webconnect. To ensure your applications are processed well before the commencement of Autumn semester, students are encouraged to submit their applications as early as possible. Late applications will not be accepted. Late applications will not be accepted.

If you would like to know more about the Honours program itself please check out the website: http://future.uws.edu.au/future_students_home/honours and our school website: http://www.uws.edu.au/ssh/school_of_science_and_health/honours If there are any further questions you need answered, please do not hesitate to contact Sabine Piller [email protected] (Science or Medical Science), or Graham Jones [email protected] (Health Science)

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Contents (projects are listed alphabetically by Supervisor)

Projects Offered at Campbelltown Ruthenium compounds with biological activity: ........................................................................................... 10

Complexes for recognition and visualisation of cellular components .......................................................... 11

The design, synthesis and characterisation of platinum(IV) prodrugs .......................................................... 12

Title of Project: Development of diagnostic radiopharmaceuticals .............................................................. 13

Synthesising tetradentates for coordination to transition metals ................................................................ 15

The social and spatial patterning of acupuncture clinics in New South Wales ............................................. 16

Social inequalities in child health .................................................................................................................. 17

Understanding the health promoting and health damaging features of new built environments in western Sydney: The Healthy Environments and Active Living (HEAL) Study ............................................................ 18

Healthier lifestyles or health-selective migration among residents of new built environments in western Sydney? The Healthy Environments and Active Living (HEAL) Study ............................................................ 19

Use of health care and expectations of new health services in new built environments: The Healthy Environments and Active Living (HEAL) Study .............................................................................................. 20

Social inequalities in healthy ageing ............................................................................................................. 21

Metabolomic analysis of aluminium’s effect on the cell............................................................................... 22

Cellular accumulation of aluminium under conditions of oxidative stress ................................................... 23

Interpersonal trust and perceived risk in healthcare decision-making ......................................................... 24

A novel approach to investigate the neuronal information encoding and analyses mechanisms in human nervous system ............................................................................................................................................. 25

Tactile sensory system and neural mechanisms underpinning hand dexterity in humans .......................... 26

Information encoding by temporal structure of afferent spike trains evoked by complex vibrotactile stimuli ............................................................................................................................................................ 27

Assessing the Chinese Medicine Quality of Life (ChQOL) Instrument .......................................................... 28

Survey of Chinese medicinal products in Australia ....................................................................................... 29

The effect of a supraorbital transcutaneous stimulator on cervicogenic headaches ................................... 30

The effect of taping/electrical stimulation on cortical excitability in subjects with lateral epicondylgia (tennis elbow) ................................................................................................................................................ 31

Does leg dominance affect performance of single leg hopping to exhaustion? ........................................... 33

Statistical determination of ground contact events during dynamic landing tasks. ..................................... 35

Identifying protein complexes critical to calcium-triggered exocytosis........................................................ 36

Does calf muscle stiffness affect lower limb function? ................................................................................. 37

Estimating the age of an individual from x-rays of the femur and the humerus .......................................... 38

Mechanism of cell cycle re-entry by quiescent prostate cancer cells ........................................................... 39

Allied health students’ attitudes and interests in working with people with a disability ............................. 40

Translating research knowledge into policy and practice: exploring Innovative Knowledge translation (KT) strategies ....................................................................................................................................................... 41

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Disability, health and public health ............................................................................................................... 42

Molecular characterisation of a component in a recently discovered DNA repair complex ........................ 43

Investigating physical activity and health (several topics available) ............................................................. 44

Assessing complementary medicine safety and efficacy related information available on the internet for consumers ..................................................................................................................................................... 45

Functional characterisation of novel transcription regulatory sequences identified in genome-wide genetic association studies. ....................................................................................................................................... 46

Dechlorination of Hexachlorobenzene Derivatives by Catalysed Electroreduction with Silver and Nanoelectrodes ............................................................................................................................................. 47

Development of analytical methods for characterising the quality of medicinal herbs. .............................. 48

Exploring evidence of safety on use of Chinese herbal medicine for women with breast cancer ............... 49

Mechanism of actions of tanshinones and related products ........................................................................ 50

Validation of mental chronometry test ......................................................................................................... 51

A Cluster Randomised Controlled Trial of a School-based Physical Activity Intervention in At-risk Communities: The Adolescent Motivation in Physical EDucation (AMPED) Program .................................. 53

Quantification of training loads and fatigue during training in AFL and NRL players ................................... 54

Individualisation of work-rate during match-play in AFL players ................................................................. 56

The effect of a soccer half-time re-warm-up upon thermoregulation and performance. ........................... 58

Investigating the interactions of the Wnt Pathway and Docetaxel – Uncovering prostate cancer signalling ....................................................................................................................................................................... 59

The reliability of voluntary activation measures within a cycling based measurement model .................... 61

Does lifting heavy weight matter if volume is the same? ............................................................................. 62

Postural control of the trunk muscles and prolonged standing .................................................................... 63

Validation of commercially available wrist-worn physical activity monitors in free-living environments. .. 64

Older adults’ perceived intensity during dance and its relation to objective measured intensity level by accelerometers and 6-minute walking test (6MWT). ................................................................................... 65

Testing system-based approach to prevent weight gain in GPs’ clinics – a pilot trail .................................. 66

Validation of commercially available wrist worn physical activity monitors in controlled environments. .. 67

To what extend a single measure of perceived physical activity status predict functional capacity, fitness levels and cognitive status. ........................................................................................................................... 68

Context and outcomes of home-based unsupervised exercise / physical activity programs delivered to older adults (65+): a systematic review ........................................................................................................ 69

Water Disinfection Using Solar Energy .......................................................................................................... 70

Genes associated with toxicity in cyanobacteria .......................................................................................... 71

The expression of myosin heavy chain isoforms in mdx skeletal muscle: a semiquantitative analysis. ....... 72

Examination of the similarity between the interaction of Human THP1 monocytes with pathogenic fungi and Trichomonas vaginalis with pathogenic fungi. ....................................................................................... 75

Interactions of tear proteins for antimicrobial defence at the ocular surface ............................................. 76

Prevention of neurodegeneration in Alzheimer’s disease by a combination of anti-inflammatory antioxidants ................................................................................................................................................... 77

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Consequences of chronic neuroinflammation on the brain: implications on Alzheimer's disease .............. 79

Identification of novel neuroprotective genes .............................................................................................. 82

Tropical rainforest plants as a source of anti-inflammatory compounds for the treatment of Alzheimer’s disease ........................................................................................................................................................... 83

Role of Bacterial Pyocyanin in Modulating Fibroblast Function and Survival ............................................... 84

Microvascular Endothelial Cell Responses to Bacterial Pyocyanin ............................................................... 85

Efficacy of Silver-Based Wound Materials against Pseudomonas aeruginosa .............................................. 86

Characterising lipid droplets found in sensory neuropathies ....................................................................... 87

Determining cytoskeletal changes to cellular architecture due to PH domain dynamin 2 mutations ......... 89

Identifying changes to the neuronal cytoskeleton cause by mutations in the house-keeping protein, SPTLC1 ........................................................................................................................................................... 90

Use of stem cell-derived lens epithelial cells for anti-cataract drug development. ..................................... 91

Characterisation of interstitial cells of Cajal within stem cell-derived intestinal tissue. .............................. 92

Production and purification of stem cell-derived endothelial cells to treat vascular disease. ..................... 93

Competing epistemologies, CAM and interdiscinplinarity in 21st century health care ................................ 94

Hydration status and thermoregulation in Indoor Hockey Goalies. ............................................................. 96

The interaction between mitochondrial function and sphingolipid metabolism. Implications for programmed cell death and human diseases. .............................................................................................. 97

Investigating the link between DNA synthesis/repair, redox balance and production of free radicals ....... 98

Investigating the role of yeast suicide proteins mitochondrial function and programmed cell death, and implications for antifungal drug therapy ...................................................................................................... 99

Investigating the link between lipid metabolism, redox balance and production of free radicals ............ 100

Protein arginine methylation – a key player in cellular events ................................................................... 101

Investigation of diffusive averaging and viscosity effects in bimodal polymer solutions ........................... 103

Investigating Restricted Diffusion using NMR Techniques.......................................................................... 104

Studying Ice Nucleation Protein Motifs with NMR Diffusion Measurements............................................. 106

Investigating Biostructures using NMR/MRI ............................................................................................... 107

MRI-based Electron Density Mapping for Radiotherapy Treatment Planning ........................................... 108

NMR Simulation using Symbolic Algebra .................................................................................................... 110

Expanding the Boundaries and Applications of Diffusion NMR .................................................................. 111

Brain-boosting to enhance learning ............................................................................................................ 113

Boosting the effects of exercise with non-invasive brain stimulation in knee osteoarthritis ..................... 114

Treating chronic headache from the top-down and the bottom-up .......................................................... 115

Muscle oxygenation and Intermittent Hypoxic Training: Role of acid-base balance .................................. 116

The role of acupuncture with managing cardio-vascular outcomes in women .......................................... 117

The patient-practitioner relationship .......................................................................................................... 118

How to dismantle a parasite. ...................................................................................................................... 119

Baroreflex control of muscle sympathetic nerve activity: effect of time of day? ....................................... 120

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The meaning of participation in craft/hobby activities amongst baby boomers living in Western Sydney: a qualitative study. 121

Sudden and Unexpected Death in Western Sydney Infants: a survey of risk reduction factor knowledge in multicultural western Sydney: “5 years on” ............................................................................................... 123

Tornadoes and health: The Australian experience. ................................................................................... 125

Cloning and characterisation of putative aluminium transporter in Saccharomyces cerevisiae ................ 127

Neurons under the metal overload ............................................................................................................. 128

Decode Nature’s Way of Detoxification – NMR Studies on Dissolved Organic Matter in Australian Aquatic Systems ........................................................................................................................................................ 129

Quantitative Composition-Flavour Relationships: the first step to a flavour tasting machine................... 130

Advanced Water Signal Suppression in in vivo NMR Spectroscopy ............................................................ 131

Chinese herbal medicine for local treatment-related side effect in women with breast cancer: development of a clinical protocol .............................................................................................................. 132

Projects offered at Hawkesbury Campus Comparative genomics and functional analysis of “stomatal movement genes” for barley salt tolerance ..................................................................................................................................................................... 134

Carbon dioxide affected stomatal behaviour in Arabidopsis: a model system for predicting crop performance in the future climate .............................................................................................................. 135

Predators and Prey – Plants, Animals and Interactions .............................................................................. 136

A Groundwater Management and Sustainability Project to Improve Livelihood of Village Communities in India ............................................................................................................................................................. 137

Sustainable Management of Stormwater and Wetlands for Securing Irrigation Water Supplies for Sporting Ovals and Parks in the Liverpool City Council Area ..................................................................................... 138

A Groundwater Management and Sustainability Project to Improve Livelihood of Village Communities in India ............................................................................................................................................................. 139

Restoration of Cumberland Plain Woodland ground layer species ............................................................ 140

Restoration of Cumberland Plain Woodlands: impacts on soil fauna and ecosystem functioning ............ 141

Can ectomycorrhizal fungi moderate the impacts of plant parasitic nematodes on trees? ....................... 142

Native and exotic bioengineers in a changing climate ................................................................................ 143

Climate change and the early development of native and exotic mussels ................................................. 144

Evaluating teaching: beyond student evaluations ...................................................................................... 145

Shifting laboratory experiments on climate change into Sydney Harbour ................................................. 146

Coral fluorescent proteins as light inducible electron transporters ........................................................... 148

Function of coral tissue colours in light modulation of host–plant symbiosis ............................................ 149

Light induced dynamic ion flux responses of coral-algal symbiosis ............................................................ 150

Cellular research of colour pigments in corals from Kimberley, Western Australia. .................................. 151

Cellular mechanisms involved in coral stress responses to climate change ............................................... 152

High Density Titanium Dioxide for Solar Applications ................................................................................. 153

Novel Semiconducting Thin Films for Solar Applications ............................................................................ 154

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Starch digestibility and glycemic behavior of major South Asian diets ...................................................... 155

Getting Your Hands Dirty – Soil Biology & Genomics .................................................................................. 156

What does it mean to ‘understand’ a chemistry concept? ......................................................................... 157

Evaluation of the Effectiveness of Odyssey as a Learning Tool ................................................................... 159

Evaluation of Visualisation Resources Using Eye Tracking .......................................................................... 161

Circling the Globe – Ecosystem Function & Integration.............................................................................. 163

Cloning and characterisation of putative aluminium transporter in Saccharomyces cerevisiae ................ 164

Projects Offered at Parramatta Campus New methods to characterise breakfast cereals ......................................................................................... 166

Characterization of pH-responsive polymers to better understand controlled polymerization ................ 167

Photo-oxidation of sugars and polysaccharides for their characterization by capillary electrophoresis ... 168

Smart polymers as the additives of the future............................................................................................ 169

Marsupial Pouch Lipids: a source of antibiotics? ........................................................................................ 170

Characterizing polysaccharides for a better health .................................................................................... 171

Towards high quality bioplastics ................................................................................................................. 172

Effect of temperature on chain length of amylose in rice starch................................................................ 173

Smart polymers for anticancer drug delivery .............................................................................................. 174

Polysaccharide-water interactions by solid-state NMR .............................................................................. 175

Anion Detection by Temperature Control Using Smart Materials .............................................................. 176

Molecular Recognition Using Macrocyclic Compounds .............................................................................. 177

Discrete Interlocked/Intertwined Supramolecular Assemblies .................................................................. 178

Metal Directed Assembly of Discrete Supramolecular Systems ................................................................. 179

Effect Crystallite and Particle Sizes on the Electrochemical Performance of a Novel LiMnPO4 Battery Cathode Material......................................................................................................................................... 180

Investigation of the surface properties of complex lipid films .................................................................... 182

High Density Titanium Dioxide for Solar Applications ................................................................................. 183

Novel Semiconducting Thin Films for Solar Applications ............................................................................ 184

Starch digestibility and glycemic behavior of major South Asian diets ...................................................... 185

Projects offered at Penrith Campus The adaptation to the mainstream in elite sport: An Australian Aboriginal perspective ........................... 187

Pathways to Paralympic Sport: Athlete and Coach Development .............................................................. 188

Physical Activity in Physical Education: How do Teaching Styles influence Physical Activity in Western Sydney Secondary Schools? ........................................................................................................................ 189

Investigating physical activity and health (several topics available) ........................................................... 190

A Cluster Randomised Controlled Trial of a School-based Physical Activity Intervention in At-risk Communities: The Adolescent Motivation in Physical EDucation (AMPED) Program ................................ 191

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Projects Offered Externally Developing New Radio-metal PET Tracers: Ligands for Oxophillic Radio-metals ....................................... 193

Development of diagnostic radiopharmaceuticals ..................................................................................... 195

Transcriptional interference within prostate cancer intergenic linked loci ................................................ 197

Multi-morbidity in Aboriginal Patients at Orange Aboriginal Medical Service ........................................... 198

Health Needs Assessment of the Orange Aboriginal Medical Service Community .................................... 199

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Honours projects offered at

Campbelltown Campus

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Title of Project: Ruthenium compounds with biological activity: Supervisor: Janice Aldrich-Wright Email: [email protected] Co-supervisor: Michael O’Connor Email: [email protected] Campus/s project is offered and conducted: Campbelltown

Background (200 words): Ruthenium complexes are water-solubility and less cytotoxic than cisplatin, which affords them potential as antitumor metallodrugs. The reactivity of ruthenium complexes has been found to be related to their coordinate ligands with the inclusion of methyl and carboxylate groups in either the 1,10-phenanthroline or 2,2’-bipyridine found to enhance electron-donating and electron-withdrawing properties, respectively. This makes ruthenium complexes excellent candidates for study. Moreover these complexes are fluorescent – highly so in some cases and this feature can be used for imaging. Phenotypic changes after metallodrug exposure.1

Aim of Study: To synthesise and characterise ruthenium metal complexes which have the potential to be used as non-cytotoxic fluorescent imaging agents. Methods: Uses molecular modelling for design, inorganic

chemistry, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Wang, Y-H.; Cheng,C-C.; Lee,W-J.; Chiou, M-J.;Pai, C-W.; Wen,C-C.; Chen, W-L.; Chen, Y-H.; A novel

phenotype-based approach for systematically screening antiproliferation metallodrugs, Chemico-Biological Interactions (2009), 182, 84-91

2. Aldrich-Wright, J.; Vagg, R. S.; Williams, P. A. Design of chiral picen-based metal complexes for molecular recognition of α- aminoacids and nucleic acids, Coordination Chemistry Reviews (1997), 166, 361-389.

3. Atilla-Gokcumen, G.E.; Williams, D. S. ; Bregman, H.; Pagano, N. Meggers, E. Organometallic compounds with biological activity: a very selective and highly potent cellular inhibitor for glycogen synthase kinase, ChemBioChem (2006), 7, 1443 – 1450

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Title of Project: Complexes for recognition and visualisation of cellular components Supervisor: Janice Aldrich-Wright Email: [email protected] Co-supervisor: Feng Li Email: [email protected] Campus/s project is offered and conducted: Campbelltown

Background (200 words): Biochemists and cell biologists require methods with which to observe cellular function without compromising the living systems. Our aim is to facilitate the investigation of structure and function in biological systems by developing a new suite of lanthanide imaging agents for microscopy, spectroscopy and magnetic resonance imaging (MRI). We will achieve these aims through the judicious design and synthesis of multidentate ligands (ML) to form lanthanide complexes for selective cell labelling and molecular tracking. The MLs will contain 4 subunits: (i) a coordinating sphere made up of a nitrogen and carboxylic acid network, (ii) an antenna to enhance the luminescence, (iii) surface geometry can be tuned to influence cellular uptake and localisation, and (iv) an attachment moiety to provide additional functionality if required such as an amino acid. By combining MLs with lanthanides we shall be able to control the molecular recognition of imaging

agents and thus observe intracellular signalling and recognition processes in a selective manner. Aim of Study: To design new multidentate ligands that will afford metal complexes different surface topologies and features for cell visualisation. Methods: Uses molecular modelling for design, inorganic chemistry, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional 1H / 13C heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. T. Haraguchi, Cell structure and function 2002, 27, 333. 2. T. Haraguchi, T. Shimi, T. Koujin, N. Hashiguchi, Y. Hiraoka, Genes to Cells 2002, 7, 881. 3. T.-O. Ishikawa, I. P. Kumar, H. B. Machado, K.-P. Wong, D. Kusewitt, S.-C. Huang, S. M. Fischer, H. R. Herschman,

Molecular Oncology, 4, 119. 4. B. Metscher, BMC Physiology 2009, 9, 11. 5. B. Metscher, Dev Dyn 2009, 238, 632 6. M. J. Allen, K. W. MacRenaris, P. N. Venkatasubramanian, T. J. Meade, Chemistry & Biology 2004, 11, 301. 7. C. S. Bonnet, E. Toth, AJNR Am J Neuroradiol 2010, 31, 401. 8. M. S. Einar, Z. W. Youssef, M. Lisa, A. B. Jeffrey, K. Elin, A. Ayodeji, S. Henrieta, H. T. Wai, L. Yongsheng, S. Martin, H. T.

Daniel, J. d. L. Mony, W. Thomas, Neurobiology of aging 2008, 29, 836. 9. S. L. Schreiber, Nature Chemical Biology 2005, 1, 64 10. J. A. Doudna, Nature Chemical Biology 2005, 1, 300 11. S. J. Lippard, Nature Chemical Biology 2006, 2, 504

Fig. 1 Energy absorbed by a chromophore can be transferred to the Ln3+ ion, which emits at various wavelengths depending upon the lanthanide. Ln3+ = Tb3+, Eu3+, Dy3+ or Sm3+.

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Title of Project: The design, synthesis and characterisation of platinum(IV) prodrugs Supervisor: Janice Aldrich-Wright Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Platinum(II) compounds which have exceptional anticancer activity have been developed at UWS and form the basis of an international patent. Compounds have been synthesised and insights gained from the structure-activity relationships have allowed us to make modifications to the structure that have resulted in a steady improvement in anticancer activity, (assessed by in vitro cytotoxicity assay against the L1210 murine leukaemia cell line). For example, substitution at the 5 or 5, 6 positions of the intercalator, 1,10-phenathroline (phen) (Table 1, dashed line) produces compounds with increased activity. Moreover, when a chiral ancillary ligand, such as 1S,2S-diaminocyclohexane is included a further increase in activity is produced. This project will synthesise platinum(IV) compounds that can be formulated from the same starting materials. Aim of Study: To synthesise and characterise novel platinum(IV) complexes and assess their anticancer activity as a prelude to their application as prodrugs. Methods: Uses molecular modelling for design, inorganic chemistry, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel platinum(IV) complexes will be synthesised and characterised using a combination of 1H and 195Pt nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional 1H / 195Pt heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Metal Complexes and Therapeutic uses thereof, Fenton, R.R. and Aldrich-Wright, J.R. International Patent, Application

Number PCT/AU02/00167, Oct., 2002 2. Fisher, D. M.; Bedarski, P. J.; Grunert, R.; Turner, P.; Fenton, R. R.; Aldrich-Wright, J. R. Chiral platinum(II) metallointercalators

with potent in vitro cytotoxicity activity, ChemMedChem (2007), 2, 488-495. 3. Brodie, C.; Collins, J.G.; Aldrich-Wright, J.R. The biological activity of some square-planar platinum(II) metallointercalators.

Journal of the Chemical Society, Dalton Transactions (2004), 1145-1152. 4. Krause-Heuer, A. M.; Grünert, Kühne, R. S.; Buczkowska, M.; Wheate, N. J.; Le Pevelen, D.; Boag, L. R.; Fisher, D. M.;

Kasparkova, J.; Malina, J.; Bednarski, P. J. Brabec, Patrick V.; Aldrich-Wright, J. R. (2009) Studies into the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells. Journal of Medicinal Chemistry, 52, 5474-5484.

5. Talib, J.; Beck, J. L.; Urathamakul, T.; Nguyen, C. D.; Aldrich-Wright, J. R.; Mackay, J. P.; Ralph, S. F. (2009) A mass spectrometric investigation of the ability of metal complexes to modulate transcription factor activity. Chemical Communications, (37), 5546-5548.

6. Fisher, D. M.; Fenton, R. R.; Aldrich-Wright, J.R. In vivo studies of a platinum(II) metallointercalator. Chemical Communications, (2008), 43, 5613-5615.

7. Krause-Heuer, A. M.; Grant, M. P.; Orkey, N.; Aldrich-Wright, J. R. Drug delivery devices and targeting agents for platinum(II) anticancer complexes, Australian Journal of Chemistry. Invited paper (2008), 61, 675-681

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Title of Project: Development of diagnostic radiopharmaceuticals Supervisor: Janice Aldrich-Wright Email: [email protected] Co-supervisor: Ivan Greguric Email: [email protected] Co-supervisor: Ben Fraser Email: [email protected] Campus/s project is offered and conducted: ANSTO and Campbelltown Background (200 words):

Radiopharmaceuticals are made up of two components; a radioisotope (eg. fluorine-18, technetium-99m, zirconium-89) attached to a biological vector (small molecule, protein, antibody etc). The biological vector facilitates transport and uptake of the radioisotope in the body. Depending upon the type of radioisotope chosen, radiopharmaceuticals can be used for diagnosis or therapy. [18F]fluorodeoxyglucose or FDG – the world’s most commonly prescribed fluorine-18 radiopharmaceutical – is used to diagnose many forms of cancer through positron emission tomography (PET) imaging (see LHS image). FDG is preferentially taken up in cancerous cells and is used for cancer diagnosis and for monitoring treatment progression. http://upload.wikimedia.org/wikipedia/commons Developing New Fluorine-18 radiopharmaceuticals Although numerous radioisotopes are available for Positron Emission Tomography (PET) imaging, fluorine-18 remains very popular due to favourable physical properties. These include low energy positron emission (0.202 MeV), excellent decay profile (97% β+ emission),

advantageous half-life (110 mins) allowing multi-step chemical syntheses and similar steric and electronic properties to the hydroxyl group. Currently we are developing fluorine-18 radiopharmaceuticals as diagnostic imaging agents for Alzheimer’s disease (metal chelators) and depression (organic cation 3 transporter inhibitors). Our honours projects typically have 2-4 stages depending upon the rate of research progression; Stage 1 - Organic synthesis. A small compound library is synthesised and fully characterised based upon an established lead compound. Stage 2 - In vitro screening. The library of compounds are screened in biological assays to measure their potential for further development into PET imaging agents. Stage 3 – Radiolabelling. Selected compounds are radiolabelled using newly developed or established radiolabelling methodologies. Stage 4 – In vivo screening. Promising compounds from in vitro screening studies and radiolabelling studies are evaluated in animal models of disease. Aim of Study: To synthesise and characterise [18F]diagnostics PET imaging agents for Alzheimers’s disease or depression. Methods: Uses molecular modelling for design, radiochemistry and synthetic chemistry, preparative HPLC, radioHPLC, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required

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Key References: 1. C. P. Ferri, M. Prince, C. Brayne, H. Brodaty, L. Fratiglioni, M. Ganguli, K. Hall, K. Hasegawa, H. Hendrie, Y. Huang, A. Jorm,

C. Mathers, P. R. Menezes, E. Rimmer and M. Scazufca, Lancet, 2005, 366, 2112-2117. 2. L. Cai, S. Lu and V. W. Pike, Eur. J. Org. Chem., 2008, 2008, 2853-2873. 3. S. M. Ametamey, M. Honer and P. A. Schubiger, Chem. Rev., 2008, 108, 1501-1516. 4. P. W. Miller, N. J. Long, R. Vilar and A. D. Gee, Angew. Chem. Int. Ed., 2008, 47, 8998-9033. 5. A. Bush and R. Tanzi, Neurotherapeutics, 2008, 5, 421-432. 6. A. I. Bush, J. Alzheimers Dis., 2008, 15, 223-240. 7. N. Vasdev, P. Cao, E. M. van Oosten, A. A. Wilson, S. Houle, G. Hao, X. Sun, N. Slavine, M. Alhasan, P. P. Antich, F. J.

Bonte and P. Kulkarni, MedChemComm, 2012. 8. R. E. Horton, D. M. Apple, W. O. Owens, N. L. Baganz, S. Cano, N. C. Mitchell, M. Vitela, G. G. Gould, W. Koek and L.

Daws Student top-up scholarships - AINSE UNSW students undertaking honours projects in collaboration with ANSTO are eligible to apply for an honours scholarship ($5000 stipend) from The Australian Institute of Nuclear Scientists and Engineers (AINSE). Visit the website below for more information. http://www.ainse.edu.au/grad_students2/honours_scholarships

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Title of Project: Synthesising tetradentates for coordination to transition metals Supervisor: Janice Aldrich-Wright Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Of the many continuous chain tetradentates that have been reported there are three stereochemical types planar, non-planar and facultative. Planar tetradentates, because of structural inflexibility, coordinate all four donor atoms to the metal in the same plane. Non-planar tetradentates coordinate the four donor atoms tetrahedrally about a metal atom. Facultative tetradentates, because of their structural flexibility, can coordinate the four donor atoms in either a planar or non-planar arrangement. The coordination chemistry of facultative ligands, like triethylenetetramine (trien), can offer a considerable range of stereisomers by arranging their donor atoms around a metal atom in several of ways. The factor which may determine the disposition may be considered under three main headings: E-strain includes all forces defining the conformation of the chelate rings. B-strain refers to steric effects as substituents are added to the individual chelate rings will cause restrictions on the neighbouring chelate rings. C-strain is due to the incompatibility of the positioning of the donor atoms of a ligand. A balanced combination of these three effects determines the topology adopted by a tetradentate ligand on coordination and consequently the stability of the complex. Upon coordination there are three geometrical isomers in which the remaining octahedral positions are in trans (11) or symmetrical cis-α and unsymmetrical cis-β-positions (shown in the figure). Tetradentates ligands offer unique structural properties that can be applied to coordination of a number of metals. Aim of Study: To synthesise and characterise tetradentate ligands and subsequently coordinate them metals, such as ruthenium cobalt or platinum(II) and (IV) before their biological activity is determined. Methods: Uses molecular modelling for design, inorganic chemistry, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Aldrich-Wright, J. R.; Fenton, R. F.; Greguric, I. D.; Hambley, T. W.; Williams, P. A. The stereospecific synthesis of ∆-α-

{dipyrido[3,2-a:2'3'-c](6,7,8,9-tetrahydro)phenazine [N,N'-di(2-picolyl)-2,5-dimethyl-2S,5S-diaminocyclohexane] ruthenium(II)} and related β -isomers. Dalton Transactions, (2002), 4666-4671.

2. Aldrich-Wright, J.; Vagg, R. S.; Williams, P. A. Design of chiral picen-based metal complexes for molecular recognition of α- aminoacids and nucleic acids, Coordination Chemistry Reviews (1997), 166, 361-389.

3. Cross, R.J., Farrugia, L.J., Newman, P.D., Peacock, R.D., and Stirling, D. Metal Complexes of New, Chiral N2O2 Tetradentate Ligands. Inorganic Chemistry (1999). 38, 1186-1192.

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Title of Project: The social and spatial patterning of acupuncture clinics in New South Wales Supervisor: Dr Thomas Astell-Burt Email: [email protected] Co-supervisor: A/Prof Caroline Smith Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Acupuncture, a form of Traditional Chinese Medicine (TCM), is often sought to treat particular health conditions. Less is known about the social and spatial patterning of acupuncture availability within Australia. As geographic proximity to healthcare is an important determinant of health-seeking behaviour (1), it is important to understand where acupuncture clinics are available and the profiles of local communities that they serve. Aim of Study: To enrich our understanding of the social and spatial distribution of acupuncture clinics across New South Wales.

Methods: Location data on acupuncture practice outlets available in NSW will be collected via online listings and practitioner networks. This data will mapped to identify where current acupuncture practice outlets are located. Census data will be used to identify the types of population profiles located in proximity to acupuncture clinics.

Ethics Application Requirements: None Key References: 1. Kawachi I, Berkman LF. Neighborhoods and health. Oxford University Press, USA; 2003.

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Title of Project: Social inequalities in child health Supervisor: Dr Thomas Astell-Burt Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Childhood is a critical period of development which can impact health outcomes in adulthood. Small inequalities in child health can lead to wider inequalities in adult health. Therefore, tracking the emergence of social inequalities in child health is important for identifying when to make positive changes and which groups to target (1). Aim of Study: The aim of this study is to identify social inequalities in child health and to track how they change over time, from age 0 to age 12. Methods: This research will analyse data from over 10,000 participants in the Longitudinal Study of Australian Children using multilevel models. Ethics Application Requirements: Permissions to use existing de-identified data. Key References: 1. Astell-Burt T, Maynard MJ, Lenguerrand E, et al. Racism, ethnic density and psychological well-

being through adolescence: evidence from the Determinants of Adolescent Social well-being and Health longitudinal study. Ethnicity and Health 2012; 17:71-87.

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Title of Project: Understanding the health promoting and health damaging features of new built environments in western Sydney: The Healthy Environments and Active Living (HEAL) Study Supervisor: Dr Thomas Astell-Burt Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Where people live tends to shape their propensity for long, happy, and healthy lives (1). Across Australia, though especially in western Sydney, urban sprawl and car dependency have been linked to the rise of some of Australia’s ‘National Health Priority Areas’, such as obesity, cardiovascular disease and Type 2 Diabetes Mellitus. New built environments in western Sydney could help to improve health, enhance active lifestyles and narrow health inequalities, but this area is under-researched. Aim of Study: The first aim of this study is to investigate new built environments in western Sydney and to identify features of those places which may promote, or damage, population health. The second aim is to understand which population groups have access to the features that promote/damage health. Methods: Observation tools to measure features of built environments. The focus will be on a range of built environments at different stages of development across western Sydney. This information will be combined with census and other forms of existing data to create maps and to identify inequalities. Ethics Application Requirements: Permissions for the student(s) to visit selected built environments across western Sydney to conduct observations. Key References: 1. Kawachi I, Berkman LF. Neighborhoods and health. Oxford University Press, USA; 2003.

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Title of Project: Healthier lifestyles or health-selective migration among residents of new built environments in western Sydney? The Healthy Environments and Active Living (HEAL) Study Supervisor: Dr Thomas Astell-Burt Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): New towns and infrastructure are being built to accommodate rapid population growth across western Sydney. Migration to these new built environments is not random and it could be related to health. People’s health and lifestyles may also change as a result of moving (1). This health-selective migration and health-mobility could have significant implications for health inequalities and future provisions of healthcare in western Sydney, yet the area is under-researched. Aim of Study: The first aim of this study is to explore the reasons why people are moving to new built environments in western Sydney. The second is to enrich understandings on the relationship between migration, health and lifestyles, before and after the move to a new built environment. Methods: Semi-structured interviews with residents of new built environments in western Sydney will be used to explore reasons for moving to their new neighbourhoods, how they felt about their circumstances before they moved, and whether they have perceived any changes to their health and lifestyles as a result. Ethics Application Requirements: Permissions for the student(s) to visit selected built environments across western Sydney to conduct interviews. Key References: 1. Boyle P, Norman P. Migration and health. In: Brown T, McLafferty S, Moon G, eds. A companion to

health and medical geography. London: Wiley-Blackwell, 2009:346-74.

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Title of Project: Use of health care and expectations of new health services in new built environments: The Healthy Environments and Active Living (HEAL) Study Supervisor: Dr Thomas Astell-Burt Email: [email protected] Co-Supervisor: Professor Jennifer Reath Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): People’s lives are shaped by where they live (1), yet little is known about access and use of medical services within new built environments. Western Sydney is a major population growth area and, with medical services in development for these new built environments, there is a need to identify where people currently seek healthcare and what their expectations are for future service provisions in their local area. Aim of Study: The first aim of this study is to understand use of healthcare (and the reasons underlying that use) among residents of new built environments in western Sydney. The second aim is to understand what the expectations of those residents are with respect to future health service provision in their area of residence. Methods: Qualitative methods (e.g. semi-structured interviews) will be used to explore the range of uses of healthcare and reasons why people choose to consult particular clinics, in line with Penchansky and Thomas’ theories on accessibility (2). The same techniques will also be used to explore perceptions and expectations on how health services would ideally be set up within local areas to best meet the needs of the community. Ethics Application Requirements: Permissions for the student(s) to visit selected built environments across western Sydney to conduct interviews (and / or focus groups). Key References: 1. Kawachi I, Berkman LF. Neighborhoods and health. Oxford University Press, USA; 2003. 2. Thomas JW, Penchansky R. Relating satisfaction with access to utilization of services. Medical Care 1984;22(6):553-68.

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Title of Project: Social inequalities in healthy ageing Supervisor: Dr Thomas Astell-Burt Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Healthy lifestyles such as balanced diets and physical activity help to prevent, or delay, the onset of non-communicable chronic diseases. Less is known about how these healthy lifestyles co-occur among older adults, or how they vary geographically, and to what extent any clustering of lifestyles increases the risk of poor health. Aim of Study: The aim of the study is to enrich understandings on the extent to which unhealthy lifestyles cluster among older people and the neighbourhoods in which they live. Methods: This research will analyse data from over 260,000 participants in the 45 and Up Study using multilevel models. Ethics Application Requirements: Permissions to use existing, de-identified data. Key References: 1. Kawachi I, Berkman LF. Neighborhoods and health. Oxford University Press, USA; 2003.

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Title of Project: Metabolomic analysis of aluminium’s effect on the cell Supervisor: Dr Trevor Bailey Email: [email protected] Co-supervisor: Dr Ming Wu Email: [email protected] Co-supervisor: Dr Cheang Khoo Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Aluminium is ubiquitous, yet its toxicity and effect on human health have not been vigorously explored. It is still being used in anti-perspirants and as an adjuvant. As more scientific evidence becomes available, this indifference to the health effects of aluminium may change. A vast amount of research in past decades has linked aluminium to neurodegerative disorders such as Alzheimer’s disease. That research contributed to the disappearance of aluminium cookware from the shelves of department stores. However, canned beverages are still everywhere, and other sources of aluminium persist. The aluminium loading in human beings will increase gradually as climate change occurs. Soil acidification leads to Al solubility and this will in turn elevate its level in crops and water. Hence, aluminium-related health problems will intensify, and thus the effect of Al ions (Al3+) on the cell needs to be investigated thoroughly. We have been working on Al3+ toxicity for the last few years using the model organism, Saccharomyces cerevisiae (baker’s yeast). It has been clearly demonstrated that Al3+ is toxic to yeast cells. Insights into the molecular mechanisms underlying its cytotoxicity have been gained through systematic screening of the entire deletion mutant collection (5047 mutants). This project is to further understand the effect of Al3+ on cellular metabolites. Aim of Study: To gain understanding of the effect of Al3+ on the cell by profiling the metabolites in Al3+-treated and untreated control yeast cells Methods: Cytotoxicity assays and metabolite extraction will be carried out following established protocols. Metabolomic and metallomic profiling will be performed with NMR, LC-MS/MS and ICP-MS. Ethics Application Requirements: Not required Key References: Can be requested by email.

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Title of Project: Cellular accumulation of aluminium under conditions of oxidative stress Supervisor: Dr Trevor Bailey Email: [email protected]

Co-supervisor: Dr Ming Wu Email: [email protected]

Co-supervisor: Dr Cheang Khoo Email: [email protected]

Co-supervisor: Dr Cindy Kersaitis Email: [email protected]

Campus/s project is offered and conducted: Campbelltown Background (200 words):

Aluminium is ubiquitous, yet its toxicity and effect on human health have not been thoroughly explored. A vast amount of research has linked aluminium to neurodegerative disorders such as Alzheimer’s disease. We have been working on aluminium toxicity for the last few years using the eukaryotic model organism, Saccharomyces cerevisiae. Our recent work1 studied the ionomic composition in Saccharomyces cerevisiae following oxidative stress that was produced by treatment with a range of reactive oxygen species (ROS). The findings showed that different ROS resulted in distinct changes in cellular concentrations of metal ions. A particularly interesting result is a massive increase in cellular aluminium levels, which rose up to 50-fold after treatment with one particular ROS (diamide). Pre-incubation of yeast with individual elements including iron, copper, manganese and magnesium failed to block diamide-induced Al uptake, suggesting Al-specific transporters could be involved in Al uptake. The roles of oxidative stress and of aluminium in the pathogenesis of conditions such as Alzheimer’s disease make this finding particularly intriguing. This project aims to investigate the uptake of various Al(III) complexes into Saccharomyces cerevisia under conditions of oxidative stress. Aim of Study:

This project aims to systematically explore the uptake of aluminium complexes such as [Al(edta)]-, [Al(ida)2]- and [Al(mal)3], and those of several other metals, into Saccharomyces cerevisia when exposed to diamide-induced oxidative stress. Methods:

Chemical syntheses and assays will be carried out following established protocols. Metallomic profiling will be performed by ICP-MS, and compounds will be characterised by NMR. Ethics Application Requirements:

Not required Key References:

1. Ming J. Wu, Patrick J. O'Doherty, Patricia A. Murphy, Victoria Lyons, Melinda Christophersen, Peter J. Rogers, Trevor D. Bailey, Vincent J. Higgins, “Different Reactive Oxygen Species Lead to Distinct Changes of Cellular Metal Ions in the Eukaryotic Model Organism Saccharomyces cerevisiae”, International Journal of Molecular Sciences, 12, (2011), 8119-8132. Other references can be requested by email.

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Title of Project: Interpersonal trust and perceived risk in healthcare decision-making Supervisor: Dr John Bidewell Email: [email protected]

Co-supervisor: Dr Phoebe Bailey (School of Psychology) Email: [email protected]

Campus/s project is offered and conducted: Campbelltown; data collection at Bankstown. Background (200 words): How a person values risks and rewards over time affects many crucial decisions, including health, lifestyle and finance. These decisions can occur in a social context. Trust and delayed consequences have been explored in existing research. How a decision-maker perceives the trustworthiness of another person who influences their decisions may also affect perceptions of risk and uncertainty. The relationship between perceived trustworthiness and risk in decision-making has thus far been insufficiently explored in healthcare. Hypothesis: Interpersonal trust between a health professional and their patient is perceived by the patient similarly to risk and uncertainty. Where trust is high, the patient’s perception of risk towards a healthcare procedure will be reduced.

Further, various methods of measuring people’s perception of risk and reward over time have been devised, including computer-based presentations such as those in Bidewell et al. (2006). The functional equivalence of these measurement methods has yet to be established, and should be established so extraneous influences of measurement modality can be properly accounted for. Hypothesis: Different methods of presenting the same scenarios will affect subjective risk. Aims of study:

1. Measure the relationship between interpersonal trust between a healthcare professional and perceived risk in a healthcare decision scenario.

2. Measure the equivalence of different modes of presentation of fundamentally identical scenarios in healthcare.

Methods: • Design: Experimental, with fixed effects and repeated measures combined factorially. • Setting: Research laboratory, UWS School of Psychology, Bankstown Campus. • Sample: UWS undergraduate students from School of Psychology participating for course credit as

per normal practice. Potential to extend sample to older adults. • Task: Set of forced-choice decisions in response to simulated healthcare scenarios incorporating

interpersonal trust and risk presented via computer. Duration about ½ hour.

Ethics application requirements: The research involves human subjects, therefore will require ethical clearance. Standard procedure for review of Honours projects with student subjects for the UWS School of Psychology will be adopted. Risk from the project can be reasonably considered negligible. Key references:

• Bailey, P. E., Ruffman, T., & Rendell, P. G. (2013). Age-related differences in social economic decision making: The ultimatum game. The Journals of Gerontology: Series B: Psychological Sciences and Social Sciences, 68B(3), 356-363.

• Bidewell, J., Griffin, B., & Hesketh, B. (2006). Timing of retirement: Including a delay discounting perspective in retirement models. Journal of Vocational Behavior, 68(2), 368-387.

• Michaelson, L., de la Vega, A., Chatham, C. H., & Munakata, Y. (2013). Delaying gratification depends on trust. Frontiers in Psychology|Cognition, 4(Art. 355), 1-6.

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Title of Project: A novel approach to investigate the neuronal information encoding and analyses mechanisms in human nervous system Supervisor: Dr Ingvars Birznieks Email: [email protected] Co-supervisor: Dr Saad Nagi Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words):

Various features of tactile stimuli are reflected in the pattern of action potential firing in tactile afferents and in somatosensory cortical neurons; however there is no clear experimental evidence that this temporal code is exploited by the central nervous system. Over the last years we have developed a unique mechanical stimulator able to evoke precisely-controlled temporal patterns of tactile afferent spiking activity. This gives us an unprecedented methodological advantage to investigate the physiological significance of the timing of individual spikes generated by skin mechanoreceptors. By combining human psychophysical data with microneurographic recordings from single human tactile afferents, we expect to be the first to demonstrate that a sophisticated temporal analysis mechanism underpin the perception of various tactile stimuli. This study will explain a very basic sensory mechanism, and is of fundamental importance to neurophysiology. Aim of Study: To obtain neurophysiological and psychophysical evidence that sensory information is encoded by timing of individual spikes (action potentials). Methods: 1) Psychophysical tests on human subjects. 2) Human microneurography - a unique method which allows us to tap into the signals single sensory axons are sending to the brain. Using fine needle electrodes inserted into a peripheral nerve we are able to analyse tactile neural signals in awake humans with a precision and resolution previously available only in animal experiments. Ethics Application Requirements: UWS Approval No: H9429 Key References: Johansson RS & Flanagan JR. (2009). Coding and use of tactile signals from the fingertips in object manipulation tasks. Nat Rev Neurosci 10, 345-359. Birznieks I, Macefield VG, Westling G & Johansson RS. (2009). Slowly adapting mechanoreceptors in the borders of the human fingernail encode fingertip forces. J Neurosci 29, 9370-9379. Johansson RS & Birznieks I. (2004). First spikes in ensembles of human tactile afferents code complex spatial fingertip events. Nat Neurosci 7, 170-177. Vallbo AB & Johansson RS. (1984). Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum Neurobiol 3, 3-14.

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Title of Project: Tactile sensory system and neural mechanisms underpinning hand dexterity in humans Supervisor: Dr Ingvars Birznieks Email: [email protected] Co-supervisor: Dr Heba Khamis Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): The human hand is an evolutionary masterpiece. It is an extraordinary sensory organ that is used to explore the physical world using the tactile sense, but at the same time it is also the most sophisticated and versatile instrument to change the world around us via manipulation of objects. The key to the hand’s astounding functionality is highly specialised sensory system and sensorimotor control algorithms that govern hand actions. The dexterity of the human hand still remains unmatched by the most advanced artificial devices - largely because it is not understood how relevant sensory information is extracted and utilised. There are many things to discover – not just to increase our understanding of how sensory information is encoded and analysed by the brain, but also to help people who have lost part of their sensory function due to illness or trauma. Engineers can also borrow some astonishing ideas from biological systems and use them to develop future technologies like artificial sensors and control algorithms for prosthesis and robotic manipulators resembling functionality of human hand. Aim of Study: The overall goal of our research is to unravel the neural sensory mechanisms that endow humans with their extraordinary ability to manipulate physical objects with their hands. In particular the main aim of the proposed study is to investigate how tactile receptors in the fingertip skin encode object properties relevant for manipulation such as softness, roughness and friction, and how this information is analyzed by the brain. Methods: A specific methodological signature of proposed research project is the use of microneurography - a unique method which allows us to tap into the signals single sensory axons are sending to the brain. Using fine needle electrodes inserted into a peripheral nerve we are able to analyse tactile neural signals in awake humans with a precision and resolution previously available only in animal experiments. Ethics Application Requirements: UWS Approval No: H9967 Key References: Johansson RS & Flanagan JR. (2009). Coding and use of tactile signals from the fingertips in object manipulation tasks. Nat Rev Neurosci 10, 345-359. Birznieks I, Macefield VG, Westling G & Johansson RS. (2009). Slowly adapting mechanoreceptors in the borders of the human fingernail encode fingertip forces. J Neurosci 29, 9370-9379. Johansson RS & Birznieks I. (2004). First spikes in ensembles of human tactile afferents code complex spatial fingertip events. Nat Neurosci 7, 170-177. Vallbo AB & Johansson RS. (1984). Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum Neurobiol 3, 3-14.

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Title of Project: Information encoding by temporal structure of afferent spike trains evoked by complex vibrotactile stimuli Supervisor: Dr Ingvars Birznieks Email: [email protected] Co-supervisor: Dr Saad Nagi Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words):

The fundamental questions this study will address have captivated the sensory neuroscience research community for many years, yet nobody has succeeded to prove that the temporal pattern in which individual nerve impulses follow each other determines the perception of vibrotactile frequency. We have preliminary evidence that such temporal encoding mechanism, based on the timing of spikes in the peripheral afferent rather than the mean discharge rate, as currently believed, plays the decisive role in determining the perceived frequency of vibrotactile stimuli.

Temporal encoding is an emerging field in neuroscience, and it is increasingly apparent that the temporal features of spike trains play a significant role in signalling various stimulus features. Our own studies have showed that relative time at which afferents discharge in the population can encode contact force magnitude and direction as well geometrical shape of the contact surface. Aim of Study: To obtain neurophysiological and psychophysical evidence that properties of vibrotactile stimuli are encoded by timing of individual spikes (action potentials) transmitted by sensory neurons. Methods: 1) Psychophysical tests on human subjects. 2) Human microneurography - a unique method which allows us to tap into the signals single sensory axons are sending to the brain. Using fine needle electrodes inserted into a peripheral nerve we are able to analyse tactile neural signals in awake humans with a precision and resolution previously available only in animal experiments. Ethics Application Requirements: UWS Approval No: H9429 Key References: Johansson RS & Flanagan JR. (2009). Coding and use of tactile signals from the fingertips in object manipulation tasks. Nat Rev Neurosci 10, 345-359. Birznieks I, Macefield VG, Westling G & Johansson RS. (2009). Slowly adapting mechanoreceptors in the borders of the human fingernail encode fingertip forces. J Neurosci 29, 9370-9379. Johansson RS & Birznieks I. (2004). First spikes in ensembles of human tactile afferents code complex spatial fingertip events. Nat Neurosci 7, 170-177. Vallbo AB & Johansson RS. (1984). Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum Neurobiol 3, 3-14.

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Title of Project: Assessing the Chinese Medicine Quality of Life (ChQOL) Instrument Supervisor: Prof. Kelvin Chan Email: [email protected] Co-supervisor: Dr Tina Naumovski Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): In order to promote a wider understanding of the principles and practice of Chinese medicine (CM), we need to fill the knowledge gaps between Western medical and CM treatments [1]. The health-related quality of life instrument based on CM diagnosis and treatment concepts (ChQOL) can bridge these gaps based on individual Patients’ Reported Outcomes (RPOs). When PROs are linked with the patients’ progress, it is possible to assess the efficacy of CM treatment [2]. The ChQOL is based on the principles of individualised diagnosis and treatment practice in CM, and is accepted world-wide for assessing health-related QOL [3]. The present research will assess if the English version of the ChQOL can be adopted for local use. Monitoring the patient before and after treatment will provide the effective assessment of the CM treatment. Aim of Study: To investigate whether the ChQOL can be adopted for local use as health-related QOL instrument for patients who attend Chinese medicine clinics. Methods: The published Chinese language version of the ChQOL instrument has now been translated into English and back-translation and validation is being carried out. Recruitment: The healthy individuals will be recruited in the university community and patients who visit the university clinic. All the subjects involved are adults from 18 to 70 years old, and are able to read and understand the instrument. Instrument: The subjects are required to answer 50 short questions relating to their health. The score for each question ranges from 1 to 5. Additional data related to gender, age, marital status, education level, occupation, lifestyle and self-reported health state will be collected. Analysis: The students involved in the project are required to collect the data, and will be shown the techniques of analysis. Ethics Application Requirements: Ethics has been obtained for the project. Key References:

1. Chan K. Chinese medicinal materials and their interface with Western medical concepts. J. Ethno-Pharmacol. 2005, 96: 1-18.

2. Zhao L & Chan K. Building a bridge for integrating Chinese medicine into conventional healthcare: Observation drawn from the development of the Chinese Quality of Life Instrument. Amer.J.Chin.Med. 2005, 33:897-902.

3. Leung KF et al. Development and validation of Chinese quality of life instrument. BioMed Central-Health and Quality of Life Outcomes 2005, 3:26; doi:10.1186/1477-7525-3-26

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Title of Project: Survey of Chinese medicinal products in Australia Supervisor: Prof. Kelvin Chan Email: [email protected] Co-supervisor: Dr Tina Naumovski Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Traditional Chinese medicine (TCM) is one of the most widespread forms of complementary medicines accessed in Australia. A recent study showed that Chinese medicinal materials (CMM) was the second most common form of herbal medicine used (27% of users) in Australia after Western herbal medicines [1]. However, there is no information on what products are used and/or available in Australia. As demand increases, there are issues with the lack of supply of good quality plant materials and substitution with benign or harmful products may result [2, 3]. These substitutes may produce toxicity and affect the efficacy of the products, rendering them ineffective for medicinal use [4]. There is an urgent need, worldwide, for information that enables researchers and regulatory authorities to discern the supply and quality of CMM products used in TCM practice; this is essential if guidelines and protocols are to be developed and disseminated to healthcare workers [5, 6]. Aim of Study: to obtain information about the supply of Chinese medicinal materials to establish benchmarks for traditional Chinese medicine practice and policy in Australia. Methods: Questionnaires have been developed to be given to two main groups: importers of CMM and food importers. The student will distribute the questionnaires and follow up on responses. There may be one-to-one interviews with the participants. The data analysis will require some statistical analysis. Ethics Application Requirements: The proposal is undergoing ethics review. Key References: 1. Zhang AL, Story DF, Lin V, Vitetta L, Xue CC (2008) A population survey on the use of 24 common medicinal herbs in Australia. Pharmacoepidemiology and Drug Safety, 17(10): 1006-13. 2. Leung P-C and Cheung KF (2008) Good agriculture practice-GAP. Does it ensure a perfect supply of medicinal herbs for research and drug development? International Journal of Applied Research in Natural Products, 3(2): 1-8. 3. Chan K (2005) Chinese medicinal materials and their interface with Western medical concepts. Journal of Ethnopharmacology, 96: 1-18. 4. Shaw D (2010) Toxicological risks of Chinese herbs. Planta Medica, 76(17): 2012-2018. 5. Chan K, Leung K, Zhao S (2009) Harmonization of monographic standards is needed to ensure the quality of Chinese medicinal materials. Chinese Medicine, p 1 of 5. 6. Fan TP, Deal G, Koo HL, Rees D, Sun H, Chen S, Dou JH, Makarov VG, Pozharitskaya ON, Shikov AN, Kim YS, Huang YT, Chang YS, Jia W, Dias A, Wong VC, Chan K (2012) Future development of global regulations of Chinese herbal products. Journal of Ethnopharmacology, 140: 568-586 7. Good Practice in Traditional Chinese medicine research in the Post-genomic Era (GP-TCM): http://www.gp-tcm.org.

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Title of Project: The effect of a supraorbital transcutaneous stimulator on cervicogenic headaches Supervisor: Professor Lucy Chipchase Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): A new supraorbital transcutaneous stimulator has been produced and is achieving positive results in the prevention and treatment of migraine. Cervicogenic headache is a secondary headache characterised by unilateral headache and signs and symptoms of neck involvement. Physical therapies including massage and manipulation are recommended as first line management for this condition. However, no studies have determined as yet the effectiveness of this new stimulator which may be a useful adjunct to traditional interventions. Aim of Study: The aim of this study is to evaluate the effectiveness of supraorbital transcutaneous stimulation when used alone or in conjunction with manual therapy. Methods: This study (depending on recruitment) will involve a series of single case studies. Ethics Application Requirements: Ethics has already been gained for this study. Key References: Schoenen et al: Migraine prevention with a supraorbital transcutaneous stimulator; a randomised controlled trial. Neurology. 2013: 80: epub ahead of print. Cahibi and Russell (2013): Manual therapies for cervicogenic headache: a systematic review. J Headache Pain 13: 351-359. Jull et al (2002): A randomised controlled trial of exercise and manipulative therapy for cerviogenic headache. Spine. 27: 17: 1835-43

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Title of Project: The effect of taping/electrical stimulation on cortical excitability in subjects with lateral epicondylgia (tennis elbow) Supervisor: Professor Lucy Chipchase Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Lateral epicondylagia (LE) or ‘tennis elbow’ is a prevalent and disabling arm syndrome with high rates of symptom chronicity and recurrence. Traditionally, LE was described as a local insertional tendinopathy with morphological changes evident in the tendon of extensor carpi radialis brevis (ECRB) (Nirschl and Pettrone, 1979, Regan et al., 1992, Connell et al., 2001, Zeisig et al., 2006). However, there is increasing evidence of supraspinal involvement. For instance, motor dysfunction present in unilateral LE is frequently bilateral; affects both local and remote upper limb muscles and persists for up to 6 months after resolution of local tendon symptoms (Pienimaki et al., 1997, Bisset et al., 2006, Alizadehkhaiyat et al., 2007). Our work has demonstrated (paper under review) altered motor cortical excitability and organisation to ECRB and extensor digitorum (ED) when participants with LE are compared to healthy, age and gender matched subjects with no arm pain. Our data provides evidence that cortical organisation is maladaptive in chronic LE and provides options for the development of treatments that restore cortical organisation. Two therapies commonly used for LE are electrical stimulation and taping. The mechanism underpinning the effect of these interventions has been assumed to be peripheral. However, afferent input (sensory stimulation) has been demonstrated to be a key driver of cortical (central) plastic change. Thus, this study aims to evaluate the effect of taping and electrical stimulation on clinical measures of LE and cortical excitability. Aim of Study: The aim of this study is to evaluate the effect of taping and electrical stimulation on clinical measures of LE and cortical excitability. Methods: Participants with LE will be invited to participate in the study. Participants will be included if they report unilateral elbow pain lasting longer than 6 weeks with pain over the lateral humeral epicondyle provoked by two of the following activities: gripping, resisted wrist or middle finger extension or palpation in conjunction with reduced pain free grip on the affected side. Using a same subject pre-post test design, transcranial magnetic stimulation (TMS) will be used to measure the responsiveness of corticomotor pathway to ECRB and ED muscles before and after 30 minutes of electrical stimulation or therapeutic taping or a sham condition. Each intervention will be applied in random order, at least three days apart. Clinical measures of LE will include:

• Pain intensity measured by a visual analogue scale. • Patient Rated Tennis Elbow Evaluation • Quantitative Sensory Testing including pressure pain thresholds and sensory analgesia. • Grip Strength

Ethics Application Requirements: This study has ethics approval but may require an amendment (H10184). Please note, that the project could be shared between two students if there is more than one interested. Key References: These references provide you with an idea of the methods to be used. TMS is a safe and non-invasive method for assessing cortical excitability.

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1. Vicenzino B et al (2003): Initial effects of elbow taping on pain free grip strength and pressure pain threshold. Journal of Orthopaedic and Sports Physical Therapy 33: 400-407.

2. Bisset LM, Russell T, Bradley S, Ha B, Vicenzino BT. Bilateral sensorimotor abnormalities in unilateral lateral epicondylalgia. Arch Phys Med Rehabil. 2006;87(4):490-5.

3. Chipchase LS, Schabrun SM and Hodges PW (2011): Corticospinal excitability is dependent on the parameters of peripheral

electrical stimulation: a preliminary study. Archives of Physical Medicine and Rehabilitation 92 (9): 1423-1430

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Title of Project: Does leg dominance affect performance of single leg hopping to exhaustion? Supervisor: Dr Peter Clothier Email: [email protected] Co-supervisor: Amitabh Gupta Email: [email protected]

Campus/s project is offered and conducted: Campbelltown

Background (200 words): The concept of leg dominance has been examined extensively in the literature. Research has investigated or demonstrated the effects of leg dominance on injury risk (Brophy et al., 2010; Ruedl et al., 2012) and during gait (Gundersen et al., 1989; Sadeghi et al., 2000), landing (Ford, Myer & Hewett, 2003), postural control (Hoffman et al., 1998), and hopping (Hobara, Inoue & Kanosue, 2013; van der Haast, Gokeler & Hoi, 2007). Hopping is considered a robust model for examining lower limb function because it is a dynamic, highly controllable task with low performance and measures variability (Oliver & Smith, 2010). However, no investigations have aimed to examine leg bi-lateral performance differences during single leg hopping to volitional exhaustion. Determination that leg dominance has no effect on single leg hopping to volitional exhaustion would enable future studies to use within subject, repeated measures study designs whereby any leg can act as a control condition for the other. This design provides a robust model that would eliminate order and fatigue effects from performing repeated trials on the same leg. Conversely, determination that leg dominance does effect performance of single leg hopping to exhaustion would necessitate that research design accommodates these differences with respect to methodological protocols. Aim of Study: The aim of this study is to determine whether leg dominance affects kinematic, kinetic and neuromuscular performance characteristics during single leg hopping to exhaustion. Methods: A minimum of 30 physically active individuals from a selected population (Netballers, Footballers, Dancers, University students, or other) will be recruited for participation in this study. Following familiarisation trials, experimental trials will require participants to perform one left and one right leg sub-maximal efforts of single leg, on-the-spot hopping. Each hopping trial will be performed on a force platform (Kistler model 9286B) at 2.2 Hz in time with an audible metronome to a self-reported level of exhaustion. Synchronous recording of surface electromyography of five lower limb muscles and lower body motion capture (Optotrak) will be obtained. Data analysis will be performed to examine kinematic, kinetic and neuromuscular characteristics between the left and right legs. Ethics Application Requirements: This investigation will require application to the UWS HREC. Application and approval is expected by March 2014. Key References: Brophy, R., Silvers, H. J., Gonzales, T., & Mandelbaum, B. R. (2010). Gender influences: the role of leg dominance in ACL injury among soccer players. Br J Sports Med, 44, 694–697. Ford, K. R., Myer, G. D., & Hewett, T. E. (2003). Valgus knee motion during landing in high school female and male basketball players. Medicine & Science in Sports & Exercise, 35(10), 1745-1750. Gundersen, L. A., Valle, D. R., Barr, A. E., Danoff, J. V., Stanhope, S. J., Snyder-Mackler, L. (1989). Bilateral analysis of the knee and ankle during gait: an examination of the relationship between lateral dominance and symmetry. Physical Therapy, 69(8), 640–50.

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Hobara, H., Inoue, K., & Kanosue, K. (2013). Effect of hopping frequency on bilateral differences in leg stiffness. J Appl Biomech, 29(1), 55-60. Hoffman, M., Schrader, J., Applegate, T., & Koceja, D. (1998). Unilateral postural control of the functionally dominant and nondominant extremities of healthy subjects. Journal of Athletic Training, 33(4), 319–322. Oliver, J. L., Smith, P. M. (2010). Neural control of leg stiffness during hopping in boys and men. Journal of Electromyography & Kinesiology, 20, 973-979. Ruedl, G., Webhofer, M., Helle, K., Strobl, M., Schranz, A., Fink, C., Gatterer, H., & Burtscher, M. (2102). Dominance is a risk factor for noncontact anterior cruciate ligament injuries in female recreational skiers. Am J Sports Med, 40(6), 1269-1273. Sadeghi, H., Allard, P., Prince, F., & Labelle, H. (2000). Symmetry and limb dominance in able-bodied gait: a review. Gait and Posture, 12, 34–45. van der Harst, J. J., Gokeler, A., & Hof, A. L. (2007). Leg kinematics and kinetics in landing from a single-leg hop for distance. A comparison between dominant and non-dominant leg. Clinical Biomechanics, 22(6), 674-680.

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Title of Project: Statistical determination of ground contact events during dynamic landing tasks. Supervisor: Dr Peter Clothier Email: [email protected] Co-supervisor: Amitabh Gupta Email: [email protected]

Campus/s project is offered and conducted: Campbelltown

Background (200 words): Accurate detection of gait events is essential for the analysis and interpretation of kinetic measures recorded during dynamic activities. Accurate identification of gait events allows the determination of other measures such as kinematics and forces (Zeni, Richards, & Higginson, 2008). Several experimental methods have been reported which permit the detection of gait events. These include foot switches (Hausdorff, Ladin, & Wei, 1995), gyroscopes (Tong, & Granat, 1999) and computational methods from motion capture data (Hreljac, & Marshall, 2000; Hreljac, & Stergiou, 2002). There are limitations with the previous methods and therefore the use of ground reaction force (GRF) data in determining gait events is the gold standard (Hansen, Childress, & Meier, 2002; Hreljac & Stergiou, 2002). Determination of gait events using GRF is typically made by manual inspection of the force-time graph. Alternately, vertical GRF data above a nominated threshold has been used to define contact period (Zeni, Richards, & Higginson, 2008). This is prone to systematic error and may have limited sensitivity to contact events during high speed tasks such as hopping. Therefore, a need exists to develop a method for determining gait events from GRF data. The ability to accurately determine gait events has not previously been investigated during single-leg hopping. Aim of Study: The aim of this study is to assess different methods for determining gait events during dynamic landings tasks. Methods: This project provides a unique opportunity to complete research that is the cornerstone for analysis and interpretation of recorded biomechanics data. Kinetic data that has been collected during trials of single leg hopping will be analysed to determine gait events using three different mathematical methods developed by the research supervisors. Appropriate statistical analysis will be used to compare the three methods. Ethics Application Requirements: This investigation will require application to the UWS HREC. Application and approval is expected by March 2014. Key References: Hausdorff, J. M., Ladin, Z., & Wei, J. Y. (1995). Footswitch system for measurement of the temporal

parameters of gait. Journal of Biomechanics, 28, 347–352. Hreljac, A., & Marshall, R. N. (2000). Algorithms to determine event timing during normal walking using

kinematic data. Journal of Biomechanics, 33, 783–786. Hreljac, A., & Stergiou, N. (2002). Phase determination during normal running using kinematic data.

Medical and Biological Engineering and Computing, 38(5), 503-506. Tong, K., & Granat, M. H. (1999). A practical gait analysis system using gyroscopes. Medical Engineering

and Physics, 21, 87–94. Zeni Jr., J. A., Richards, J. G., & Higgninson, J. S. (2008). Two simple methods for determining gait events

during treadmill and overground walking using kinematic data. Gait and Posture, 27(4), 710-714.

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Title of Project: Identifying protein complexes critical to calcium-triggered exocytosis Supervisor: Prof Jens R. Coorssen Email: [email protected] Co-supervisor: Dr. C. Malladi Email: [email protected] Campus/s project is offered and conducted: School of Medicine, Campbelltown Background (200 words): Calcium-triggered exocytosis, the basis of CNS function, is one of the most fundamental of cellular process yet a molecular understanding of the underlying molecular mechanisms is still lacking. We are isolating protein complexes associated with vesicle docking, priming and triggered fusion. Aim of Study: To unambiguously identify components of protein complexes associated with key steps in the triggered release pathway. Methods: Native gel electrophoresis as well as affinity tools, coupled with Western blotting and mass spectrometry. Some work with rapid freeze, freeze-substitution electron microscopy is also possible. Ethics Application Requirements: n/a Key References: Please see any work from the Coorssen lab concerning exocytosis, regulated membrane fusion, and proteomics.

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Title of Project: Does calf muscle stiffness affect lower limb function? Supervisor: Jack Crosbie Email: [email protected] Co-supervisors: Peter Clothier Email: [email protected] Co-supervisors: Amitabh Gupta Email: [email protected] Campus/s project is offered and conducted: Campbelltown Campus

Background:

Stiffness or contracture of the calf muscles is a major problem in many clinical situations such as following stroke, in children with cerebral palsy, or after ankle injuries in athletes. Such limitations can interfere with the performance of functional tasks, such as walking, running and stair climbing, by increasing the demand on the calf muscles and restricting forward rotation of the shank at the ankle when the foot is weight-bearing.

There have been few studies investigating the consequences of variations in calf muscle compliance on task performance, even in able-bodied subjects. Investigation of the influence of normal variations in ankle flexibility on the performance of a wider range of mobility tasks is required to inform the clinical management of people who develop contracture of these muscles.

Comparison of gait-related activities of otherwise healthy people with “flexible” and “stiff” calf muscles would provide important information, allowing a better understanding of the influence of the passive mechanical characteristics of the calf on normal functions. Some preliminary work has been carried out (Moseley et al, 2001; 2003), but the activities tested to date have been relatively undemanding. More focussed testing is needed to extend our knowledge in this important area.

Aim of Study: To examine the effect and influence of the passive mechanical properties of the calf muscle on lower limb gait activities. Methods: The study will recruit healthy individuals. Calf muscle stiffness and ankle flexibility will be computed using a customised torque/angle measurement device and participants will also be required to perform a number of walking-related activities. Analysis will seek correlation between key gait performance variables and the passive mechanical characteristics of the calf muscles. Ethics Application Requirements: Program ethics application is currently under review by the Human Ethics Committee. Key References: Moseley AM. Crosbie J, Adams R. Normative data for passive ankle plantarflexion-dorsiflexion flexibility. Clinical Biomechanics 2001; 16: 514-521.

Moseley AM, Crosbie J, Adams R. High and low ankle flexibility and motor task performance. Gait and Posture 2003; 18: 73 – 80.

Crosbie J, Alhusaini A, Dean C, Shepherd R Plantarflexor muscle and spatiotemporal gait characteristics of children with hemiplegic cerebral palsy: an observational study. Developmental Neurorehabilitation. 2012; 15: 114-118.

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Title of Project: Estimating the age of an individual from x-rays of the femur and the humerus Supervisor: Manisha Dayal Email: [email protected] Campus/s project is offered and conducted: Campbelltown Campus Background (200 words): Age estimation from skeletal remains plays an important role in the identification of an individual in forensic cases. Many external morphological markers have previously been used for estimating age. In many forensic cases, however, dismembered parts of the individual are presented to the forensic anthropologist for analyses. This makes it difficult to use the current methods available for age estimation. The internal morphology of the femur and humerus has been shown to change with age. Aim of Study: Thus the aim of this study is to investigate whether it is possible to allocate an age-range for an individual based on x-rays of the femur and humeri of South African populations. Methods: 120 digital x-rays of the femora and humeri of individuals with known age, sex and race will be analysed using a method suggested by Acsadi & Nemeskeri (1970). The proximal ends of both bones will be analysed using a description as set out by Acsadi & Nemeskeri (1970). The age ranges predicted will then be compared to the actual ages of the individuals. Further investigation into a method may also lead to a new developed method specifically for this population. Ethics Application Requirements: Ethics approval is not required for this study as the x-rays were taken as part of another study which falls under the South African Anatomy Act 1985. Key References:

1. Acsadi G, & Nemeskeri J. History of human life span and mortality. Budapest, Akademiai Kiado, 1970.

2. Krogman WM, & Iscan MY. The human skeleton in forensic medicine. Springfield, Illinois, Charles C Thomas, 1986.

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Title of Project: Mechanism of cell cycle re-entry by quiescent prostate cancer cells Supervisor: A/Prof Qihan Dong Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Cancers are made up of both actively dividing and "resting" cancer cells. These resting or quiescent cancer cells are thought to be central to relapse, after actively dividing cancer cells are eliminated by chemo- or radio-therapy. One can envisage if cell cycle re-entry by these quiescent cancer cells is blocked, cancer recurrence can be prevented or delayed. However, the regulatory signals required for quiescent cancer cells to re-enter the cell cycle have not been determined. Identification of these signals will provide needed molecular targets for preventing cancer recurrence. We have found a list of genes that are over-expressed in advanced form of prostate cancer compared with either normal prostate or organ-confined prostate cancer. The role these gene products play in promoting cell cycle re-entry by quiescent prostate cancer cells is unclear. Aim of Study: To determine the effect of gene products that are over-expressed in advanced form of prostate cancer in cell cycle re-entry by quiescent prostate cancer cells. Methods: Honours students will learn cell culture and immunoblot and use these techniques to determine the identified gene product (proteins) in cell cycle re-entry by quiescent cancer cells. Ethics Application Requirements: Not required as all are in vitro studies Key References: Desoize B, Jardillier J. Multicellular resistance: a paradigm for clinical resistance? Crit Rev Oncol Hematol 2000;36:193-207.

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Title of Project: Allied health students’ attitudes and interests in working with people with a disability Supervisor: Dr. Gisselle Gallego Email: [email protected] Co-supervisor: Professor Michelle Lincoln (Usyd) Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): The implementation of the DisabilityCare Australia (DCA) is expected to generate a responsive, person-centred system that will allow people with disability to choose (a) how they get support and (b) have control over when, where and how they receive it. As the DCA is rolled out, people with disabilities living in rural areas are vulnerable to the loss of access to allied health services due to critical shortages of allied health professionals (AHPs) to provide them. AHPs, including speech pathologists, occupational therapists and physiotherapists “therapists”, are key service providers to people with disability. These therapists optimise functioning and independence for individuals and ensure they can participate as fully as possible in their communities. They also support families and carers to assist the person with disability and to promote their own well being and quality of life1, 2. However, there is some evidence that working with people with a disability is viewed as one of the least attractive work options for undergraduate speech pathology students3, 4. This highlights one important challenge of recruiting and retaining therapists to work with people with a disability, a challenge that is exacerbated in rural and remote areas. Aim of Study: is to explore allied health students’ (speech pathology, physiotherapy and occupational therapy) interest in working with people with a disability. Methods: The project will employ a mixed methods approach and will consist of two inter-related phases. The methods used will be a survey of AHP students’ including an interaction with Disabled Persons attitudinal scale and focus groups with allied health students (speech pathology, physiotherapy and occupational therapy). Ethics Application Requirements: Ethics application is needed Key References: 1. Bundy A, Hemsley B, Brentnall J, E M. Therapy services in the disability sector: Literature review. Sydney, NSW: NSW Department of Ageing, Disability and Home Care2008. 2. Australian Government Productivity Commission. Disability Care and Support - Productivity Commission Inquiry Report. Canberra2011. 3. Iacono T, Johnson H, Humphreys J, McAllister L. Recruitment of speech pathologists into positions considered less attractive. International Journal of Speech-Language Pathology. 2007;9(3):204-12. 4. Johnson H, Bloomberg K, Iacono T. Student and professional attitudes and interests in working with people with complex communication needs. International Journal of Speech-Language Pathology. 2008;10(5):286-96.

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Title of Project: Translating research knowledge into policy and practice: exploring Innovative Knowledge translation (KT) strategies Supervisor: Dr. Gisselle Gallego Email: [email protected] Co-supervisor: Dr. Angela Dew (Usyd) Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Knowledge derived from health-related research is of limited value unless it is translated into policy and practice. Knowledge translation (KT) has emerged as a paradigm to address the challenges in closing the “know-do” gap. Traditional dissemination methods of research findings often restrict audiences to fellow academics and pose a barrier to research use. Interest in arts-based approaches has grown, as one consequence of an extended epistemology that recognises different forms of knowledge. Such approaches harness the power of the arts in enhancing representation, generating new insights and increasing understanding of phenomena. Arts-based KT strategies are being trialled in Canada. Aim of Study: This project aims to explore effective ways of communicating research findings to policy makers. The project will involve exploring the effectiveness of different methods of KT such as visual arts, info graphics and digital media. Methods: This project combines the multidisciplinary and complementary expertise it will draw on health services research, clinical research skills and sociology to inform understanding and interpretation of the findings. The project will employ a mixed methods approach and will consist of two inter-related phases. The methods used will semi-structure interviews, and a survey including a discrete choice experiment. Ethics Application Requirements: Ethics application is needed Key References: Vogel, J.P., A.D. Oxman, et al. (2013). Policymakers' and other stakeholders' perceptions of key considerations for health system decisions and the presentation of evidence to inform those considerations: an international survey. Health research policy and systems / BioMed Central 11, 19. Barwick, M., Peters, J. and Boydell, K.M. (2009). Getting to uptake: Do communities of practice support the implementation of evidence-based practice? Canadian Journal of the Academy of Child and Adolescent Psychiatry. 18(1):16-29. Barwick, M., Boydell, K.M., Stasiulis, E., Ferguson, H.B., Blasé, K. and Fixen, D. (2008). Research Utilization among executive directors and practitioners in children’s mental health. Implementation Science. 3:19.

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Title of Project: Disability, health and public health Supervisor: Dr. Gisselle Gallego Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Globally, there are 1 billion people with disabilities, approximately 15% of the population. One in 5 Australians have a disability with this number likely to grow, largely driven by increases in population and population ageing. This has important implications for health, public health and disability services. People with disability are four times more likely to report poor health. They have preventable health problems like anyone without a disability. People with disabilities are capable of living healthier lives and need to be included in the application of public health activities of health promotion, and prevention as well as surveillance and epidemiology. Aim of Study: is to conduct a review of the international and national literature (including grey literature) to identify current practices and describe different approaches (if available) to incorporating disability considerations into general public health activities in Australia. Methods: Systematic literature review. Ethics Application Requirements: No ethics application is needed Key References: Drum CE, Krahn GL, Bersani H (2009). Disability and public health. Washington, DC: American Public Health Association; American Association on Intellectual and Developmental Disabilities. Houghton, A. (2013). What should public health be doing for disabled people, and why aren't we? Journal of Public Health 35, 2-3. Lollar DJ, Crews JE (2003). Redefining the role of public health in disability. Annu Rev Public Health 24(1):195-208

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Title of Project: Molecular characterisation of a component in a recently discovered DNA repair complex Supervisor: Dr Roland Gamsjaeger Email: [email protected] Co-supervisor: Dr Liza Cubeddu Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): An effective DNA damage response is fundamental in maintaining genetic integrity and cellular survival. One major DNA damage repair pathway in humans is Nucleotide Excision Repair (NER). NER removes bulky lesions (e.g., ultra-violet (UV) radiation damage) and cross-links (e.g., platinum-based chemotherapeutics) in duplex DNA. Single stranded DNA binding (SSB) proteins have important roles in many DNA repair mechanisms [1]. We have identified two novel human single-stranded DNA binding proteins (hSSB1 and 2) involved in the DNA repair network [2]. We have begun to characterise hSSB2 [3] and our data implicate hSSB2 early in the NER response. Following UV damage, we show that hSSB2 locates to chromatin as part of a newly discovered complex consisting of two main proteins, INTS3 (Integrator Complex Subunit 3) and a small, uncharacterised open reading frame (ORF), called C9orf80. The molecular mechanism underpinning the assembly and function of this new protein complex are currently unknown. Aim of Study: To characterise the C9orf80 member of this new DNA repair complex. Aim 1. Recombinant protein expression of C9orf80 in a bacterial expression system. Aim 2. Biochemical characterisation of C9orf80 Aim 3. Preliminary structural characterisation of C9orf80 Methods: Molecular cloning – Routine DNA manipulation techniques to produce recombinant bacterial plasmids for recombinant protein expression in Escherichia coli Protein Expression and Purification – Techniques to Optimize recombinant protein expression in a bacterial expression system. Affinity and size exclusion chromatography. Biophysical & Structural Methods - 1D Nuclear Magnetic Spectroscopy (NMR) to determine if protein is folded, Circular Dichroism Spectropolarimetry to determine percentage secondary structure (alpha helix/ beta strand), 2D NMR to determine feasibility for structure determination. Biosensor binding experiments – To determine if C9orf80 interacts with the hSSB2 component of this complex. Ethics Application Requirements: NA Key References: 1. Ashton NW, Bolderson E, Cubeddu L, O'Byrne KJ, Richard DJ. Human single-stranded DNA binding proteins are essential for maintaining genomic stability. BMC Molecular Biology 2013; 14(1):9. 2. Richard DJ, Bolderson E, Cubeddu L, Wadsworth RI, Savage K, et al. (2008) Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature 453: 677-681. 3. Gamsjaeger R, Kariawasam R, Bang LH, Touma C, Nguyen CD, Cubeddu L & Mackay JP (2013) Semi-quantitative and quantitative analysis of protein-DNA interactions using steady-state measurements in Surface-Plasmon-Resonance competition experiments. Analytical biochemistry. doi:pii: S0003-2697(13)00237-6. [Epub ahead of print]

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Title of Project: Investigating physical activity and health (several topics available) NOTE: Projects are available for one or more Honours students Supervisor: Emma George Email: [email protected] Co-supervisor: Gregory Kolt Email: [email protected] Co-supervisor: Dr Thomas Astell-Burt Email: [email protected] Campus/s project is offered and conducted: Campbelltown or Penrith Background (200 words): The 45 and Up Study (www.45andup.org.au) is the largest ongoing study of healthy ageing in the Southern Hemisphere. Data on a range of health, quality of life, and demographic factors (including physical activity levels and time spent sedentary) has been collected from 267,153 men and women aged 45 years and over, living in NSW. Of particular interest to our research team are some of the health and well-being issues that relate to Greater Western Sydney - a culturally diverse and rapidly growing region in NSW. We are also interested in Culturally and Linguistically Diverse (CALD) groups in relation to health promoting behaviours. The Greater Western Sydney region encompasses areas of both socioeconomic advantage and disadvantage, and the population experiences high rates of overweight and obesity and is overrepresented in a range of adverse health conditions. Findings from this study will help inform the design of future health promotion initiatives and policies relevant to areas such as Greater Western Sydney with its culturally diverse population. Aim of Study: More than one Honours student can work in this area, and topics can be shaped to the expertise and interest of the students. Utilising existing baseline data from the large-scale 45 and Up Study, the aim of these projects is to examine the cross-sectional associations between physical activity and/or sedentary time and a range of health-related variables in middle-aged and older Australians. These topics could focus on issues specific to Greater Western Sydney or on topics relevant to particular population groups (e.g., CALD groups). Students with an interest in the role physical activity plays in health and an interest in epidemiology will have the opportunity to select health outcomes of interest for examination. The findings from these projects will contribute to a growing body of evidence related to the health and wellbeing of Australian adults. Methods: Students will carry out an extensive literature review in the area of their project, will use existing data from The 45 and Up Study to conduct cross-sectional analyses, and will work towards publication of their findings in a suitable journal. Students will join a strong research team and will gain good support in research training. Opportunities will exist for suitable students to progress into a PhD after completion of their Honours degree. Ethics Application Requirements: Only reciprocal ethics approval (at UWS) will be required for this project, as approval has already been obtained for the larger Study and related sub-studies. Key References: 45 and Up Study Collaborators. (2008). Cohort profile: The 45 and Up Study. International Journal of Epidemiology, 35(5), 941-947. George, E. S., Rosenkranz, R. R., & Kolt, G. S. (2013). Chronic disease and sitting time in middle-aged Australian males: findings from the 45 and Up Study. International Journal of Behavioral Nutrition and Physical Activity, 10, 20. doi: 10.1186/1479-5868-10-20.

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Title of Project: Assessing complementary medicine safety and efficacy related information available on the internet for consumers Supervisor: Dr Anthony Good Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Use of complementary medicine is widespread in Australia with reports of up to 80% of Australians consuming a complementary medicine each year[1]. However, the quality of information available on the internet available to consumers is questionable, which may pose significant and serious public health concerns. People in the Australian community have the right to be appropriately informed about the safety and efficacy of complementary medicines. The lack of focus on details of efficacy and safety of complementary medicines in the health system leads those who wish to be well informed of the complementary medicines they are taking to seek information elsewhere, which in the information age if most commonly the internet. Health information on the internet ranges from personal accounts of illnesses, consumer discussion groups, chat forums, and advertisements related to products. Aim of Study: This project aims to conduct a preliminary analysis of health regarding the safety and efficacy of complementary medicines available on the internet. Methods: Criteria for determining quality of information related to various dimensions such as content, type, scientific merit, ethical aspects with a particular focus on safety and efficacy information will be developed from the literature and applied to analyse the first 50 websites that appear using 'complementary medicine' as a search term for Australian websites. Information gathered from these websites will be compared with published data for those complementary medicines which appear most often on the first 50 websites identified above. Ethics Application Requirements: No HREC approval required as survey work based on published data and not interview data Key References: 1. Bensoussan, A.M., Stephen Towards a safer choice :the practice of traditional Chinese medicine in

Australia. 1996, Campbelltown, N.S.W. :: Faculty of Health, University of Western Sydney Macarthur. 476 p.

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Title of Project: Functional characterisation of novel transcription regulatory sequences identified in genome-wide genetic association studies. Supervisor: Graham Jones Email: [email protected] Campus/s project is offered and conducted: Campbelltown (2 Honours students) Background (200 words): Genome-wide genetic association studies (GWAs) have identified many common single nucleotide polymorphisms that increase susceptibility to common disorders such as asthma, dermatitis, inflammatory bowel disease and psoriasis. These diseases all involve immune cell deviation as well as problems in the maintenance of a healthy epithelial barrier, leading to increased susceptibility to infection by bacteria and viruses. The GWAs have provided 2 particularly interesting findings: 1) the identification of shared pathways and gene involved in the pathogenesis of these diseases; 2) the identification of many genetic polymorphisms that are located away from genes in conserved non-coding regions of the genome. The identification of many conserved non-coding regions suggests that many polymorphisms associated with common disease change the way genes are turned on or off. The effect of these polymorphisms might be particularly important in controlling the expression of genes that are required to defend a cell against infection, or to limit the damage to an epithelial cell following the immune response against an infectious agent. Aim of Study: The aim of this study is to use the results of GWAs of asthma, dermatitis, psoriasis and inflammatory bowel disease to identify and functionally test transcription regulatory elements that are important in the maintenance of a health epithelial barrier in the skin, lungs or gut following infection. Methods: Transcription regulatory elements will be identified in cultured human cell lines treated with bacterial or fungal lysates, or analogues of viral double-stranded RNA by constructing genomic libraries of DNAseI hypersensitive sites. The function of these regulatory elements will be confirmed by luciferase reporter gene assays and quantitative reverse-transcriptase-PCR reactions. The expression of genes and inflammatory cytokines in response to bacterial or fungal lysates, or analogues of viral double-stranded RNA will be visualised using immune-fluorescent microscopy. Ethics Application Requirements: None Key References: Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M, Hayden C, Willemsen G, Ang W, Kuokkanen M, Beilby J, Cheah F, de Geus EJ, Ramasamy A, Vedantam S, Salomaa V, Madden PA, Heath AC, Hopper JL, Visscher PM, Musk B, Leeder SR, Jarvelin MR, Pennell C, Boomsma DI, Hirschhorn JN, Walters H, Martin NG, James A, Jones G, Abramson MJ, Robertson CF, Dharmage SC, Brown MA, Montgomery GW, Thompson PJ; Australian Asthma Genetics Consortium. Lancet. 2011 Sep 10;378(9795):1006-14 Real-time PCR mapping of DNaseI-hypersensitive sites using a novel ligation-mediated amplification technique. Follows GA, Janes ME, Vallier L, Green AR, Gottgens B. Nucleic Acids Res. 2007;35(8):e56

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Title of Project: Dechlorination of Hexachlorobenzene Derivatives by Catalysed Electroreduction with Silver and Nanoelectrodes Supervisor: Dr Robert Kaziro Email: [email protected] Co-supervisor: Dr Cheang Khoo Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Australia has the world’s largest stockpiles of concentrated hexachlorobenzene stored amounting to 10,000 tonnes in 60,000 drums at Botany Orica/ICI plant in Sydney (Hillier, Gennissen et al. 2009 ). Cyclic voltammetry and controlled-potential electrolysis have been used to investigate the catalytic reduction of hexachlorobenzene(Matsunaga and Yasuhara 2005) (Matsunaga and Yasuhara 2005) and (Gach, Karty et al. 2008), but the multiple products were not isolated. (Sidhu 2000) uncatalytically and catalytically reduced the HCB and its substitution products by cyclic voltammetry and proposed an electroreduction mechanism. Sidhu demonstrated that the 1,4-dicyanobenzene-catalysed electoreduction of HCB and its derivatives were between 2 and 14 dm3 mol-1 s-1, whereas those for the uncatalysed electro reduction were between 2 x 10-13 and 6 x 10-7 cm s-1. The honours project is proposed concerning the application of advanced voltammeter techniques such as sc(Hillier, Gennissen et al. 2009)an, step and pulse for determining the following: Efficiency of 1,4-dicyanobenzene catalyst and reactivity of pentachloromethoxychlorobenzene with new catalysts. Efficiency of solid carbon electrode and fabrication of nanoparticle electrodes such as zinc. Identity of multiple products from 1,4-dicyanobenene electroreduction of pentachloromethoxybenzene. Controlled potential electrolysis will be used to complement the voltammetry techniques. Gach, P. C., J. A. Karty, et al. (2008). "Catalytic reduction of hexachlorobenzene and pentachlorobenzene by cobalt(I) salen electrogenerated at vitreous carbon cathodes in dimethylformamide." Journal of Electroanalytical Chemistry 612(1): 22-28. Hillier, N., J. Gennissen, et al. (2009). "Our battle with hexachlorobenzene: Citizen perspectives on toxic waste in Botany." Journal of Environmental Management 90(4): 1605-1612. Matsunaga, A. and A. Yasuhara (2005). "Dechlorination of polychlorinated organic compounds by electrochemical reduction with naphthalene radical anion as mediator." Chemosphere 59(10): 1487-1496. Sidhu, J. K. (2000). Kinetics and mechanisms of methoxide substitution and electroreduction of hexachlorobenzene, University of Western Sydney. PhD. Aim of Study: To investigate dechlorination of hexachlorobenzene derivatives by catalysed electroreduction with carbon and nanoelectrodes Methods: Cyclic voltammetry and controlled-potential electrolysis with rotating disc electrode. Mass spectrometry and gas chromatography. Nano electrode fabrication. Ethics Application Requirements: NA Key References: Sidhu (2000), Hillier (2009) and Matsunaga(2005).

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Title of Project: Development of analytical methods for characterising the quality of medicinal herbs. Supervisor: Dr. Cheang Khoo Email: [email protected] Co-supervisor: Dr. Sam Lee Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Herbal quality varies greatly and is influenced by factors such as species type, growth conditions, age of plant, time of harvest and post-harvest treatment. Characterising the quality of a herb is not as straightforward as it seems because natural products have complex composition and decisions have to be made as to which chemical(s) should be measured to infer quality, and hence medicinal efficacy. The Centre for Complementary Medicine Research (CompleMed) at UWS has developed a systematic procedure for selecting the analytes that should be monitored to indicate herbal quality. This study will select a herb and study the compositional variability of the herb sourced from different suppliers in the market place. The analyte(s) determined will be chosen using the selection criteria mentioned and the quality of the herb from different sources ranked. Analytical method development might be necessary. Pharmacological testing (for example antioxidant, free radical, scavenging and anti-inflammatory activity) will then be carried out to observe if the activity of the herb correlates with the quality ranking of the herb derived from chemical testing. The results from this study may lead to a refinement of the selection criteria developed by CompleMed. Aim of Study: Rank the quality of the herb according to its chemical characteristics and to determine if this correlates with its pharmacological ranking. Methods: Chemical characterisation by LC-PDA, LC-MS, GC-MS. Pharmacological testing methods. Ethics Application Requirements: None Key References: 1 Jeong, SC, Koyyalamudi, sr, Hughes,JM, Khoo,c. Bailey,T, Marripudi, K., Park, JP, Kim, JH, Song, CH. Antioxidant and immunomodulating activities of exo- and endopolysaccharide fractions from submerged mycelia cultures of culinary-medicinal mushrooms. International Journal of Medicinal Mushrooms, 2013;15(3): 251–266 2. Jeong, SC, Koyyalamudi1, SR, Hughes JM, Khoo, C, Bailey, T, Park, JP, Song, CH, Modulation of cytokine production and complement activity by biopolymers extracted from medicinal plants. Phytopharmacology, 2013, 4(1), 19-30 3. Patricia, D, Sang Chul Jeong SC, Lee, S, Khoo, C, and Koyyalamudi, SR, Antioxidant and anti-inflammatory activities of selected medicinal plants and fungi containing phenolic and flavonoid compounds. Chinese Medicine 2012; 7:26:1 9 4. Lee S, Khoo CS, Pearson JL, Hennell JR, Bensoussan A. Liquid chromatographic determination of narirutin and hesperidin in Zhi Ke in the form of the raw herb and of the dried aqueous extract. Journal of AOAC International. 2009; 93(3): 789-796. 5. Lee S, Khoo C S, Hennell JR, Pearson JL, Jarouche M, Halstead CW, Bensoussan. A.LC determination of albiflorin and paeoniflorin in Bai Shao (Paeonia lactiflora) as a raw herb and dried aqueous extract.Journal of AOAC International. 2009; 92(4):1027-34. 6. Hennell JR, Lee S, Khoo CS, Gray MJ, Bensoussan A. The determination of glycyrrhizic acid in Glycyrrhiza uralensis Fisch. Ex DC. (Zhi Gan Cao) root and the dried aqueous extract by LC-DAD. Journal of Pharmaceutical and Biomedical Analysis. 2008; 47(3): 495-500.

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Title of Project: Exploring evidence of safety on use of Chinese herbal medicine for women with breast cancer Supervisor: A/Professor Chun Guang Li Email: [email protected] Co-supervisor: Dr Xiaoshu Zhu Email: [email protected] Dr Yun Xu (Oncology department of Beijing Xiyuan Hospital) Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Breast cancer is the second leading cause of cancer deaths in women today [1]. With the advances in medical knowledge, the survival rates for breast cancer have been improving for the past forty years; however the side effects of many conventional therapies in treating breast cancer are still harmful and distressing which decrease quality of life in patients and increase use of health care resources [2]. Many women with breast cancer or history of breast cancer use Chinese herbal medicine (CHM) for managing adverse effects or for future prevention [3], however there are concerns about whether CHM is safe alternative for women with breast cancer in terms of potential impact on the sex hormones, given the link between higher level of sex hormones and breast cancer is well established. This project is part of a series of study under a theme of complementary and alternative medicine (CAM) research in breast cancer; it is also an international collaborative project preparing for a clinical trial in the near future. Aim of Study: To evaluate the contents of phytoestrogens in defined Chinese herbal formula Methods: An extensive literature review will be conducted to evaluate possible phytoestrogen compounds in individual herbal ingredient of the formula. Contents of potential phytoestrogens in the formula extracts will be determined by HPLC or LC-MS. Estrogenic activity in cells may also be investigated. Ethics Application Requirements: NO Key References: 1. World Health Oragnisation. Breast cancer awareness month. 2011; Available from: http://www.who.int/cancer/events/breast_cancer_month/en/. 2. Markes, M., T. Brockow, and K.L. Resch, Exercise for women receiving adjuvant therapy for breast cancer, 2006, Cochrane Database of Systematic Reviews, Issue 4. 3. Kremser, T., et al., Use of complementary therapies by Australian women with breast cancer. The Breast, 2008. 17: p. 387-391.

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Title of Project: Mechanism of actions of tanshinones and related products Supervisor: A/Prof Chun Guang Li Email: [email protected] Co-supervisor: A/Prof Dennis Chang Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Cardiovascular disease, in particular ischemic heart disease (IHD), is the leading cause of mortality and morbidity in Australia. There remains a compelling need to develop new therapeutic drugs for IHD. Tanshinones are a group of bioactive compounds isolated from Salvia miltiorrhiza, a traditionally medicinal plant used in management of angina pectoris, atherosclerosis and stroke [1]. These compounds have been shown with actions against oxidative stress and hypoxia/ischemia induced cell injury [1-2], as well as endothelial nitric oxide synthase uncoupling, which plays an important role in vascular dysfunctions in various disease conditions including diabetes [3]. Further study on the actions of these compounds or related compounds may help to develop new therapeutics for treating IHD. Aim of Study: This project aims to investigate mechanism of actions of tanshinone derivatives and other herbal extracts on regulation of oxidative stress and apoptosis in cardiac and endothelial cells. Methods: The method involves cell culture techniques, cell viability assay and assays on cell signalling molecules. Ethics Application Requirements: No Key References:

1. Hyou-Ju Jin & Li CG (2013) Tanshinone IIA and Cryptotanshinone prevent mitochondrial dysfunction in hypoxia induced H9c2 cells: Association of mitochondrial ROS, intracellular nitric oxide and calcium levels. Evidence-Based Complementary and Alternative Medicine. Vol. 2013, Article ID 610694, 11 pages, doi:10.1155/2013/610694.

2. Hyou Ju Jin, Xie XL, Ye J, Li CG (2013) TanshinoneIIA and cryptotanshinone protect against hypoxia-induced mitochondrial apoptosis in H9c2 cells. Plos One 8(1): e51720. doi:10.1371/journal.pone.0051720.

3. Zhou ZW, Xie XL, Zhou SF, Li CG (2012) Mechanism of reversal of high glucose-induced endothelial nitric oxide synthase uncoupling by tanshinone IIA in human endothelial cell line EA.hy926. Eur J Pharmacol. 697(1-3):97-105.

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Title of Project: Validation of mental chronometry test Supervisor: Associate Prof. Karen Liu Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Mental imagery (MI) is a process in which a function, a behavior, or a performance is rehearsed mentally as if the person is actually performing it (Driskell, Copper, & Moran, 1994). It is believed to enhance learning by involving the individual in actively gathering perceptual information from memory and undergoing the experience of “seeing the performance of the behaviour with the mind’s eye” (Kosslyn, Ganis, & Thompson, 2001). The technique of MI is practiced by athletes to enhance their performance through mentally practicing the body movements required for particular bodily actions when field practice is not feasible (Callow & Hardy, 2001; Ryan & Simons, 1981). MI is an innovative treatment strategy to promote function for people with neurological conditions (Liu, Chan, Lee, & Hui-Chan, 2004; Liu et al., 2009). There are various questionnaires/assessment to assess on how well participants engage in MI. However, they are mostly self-reported type of the imagery ability and do not objectively reflect on their mental imagery ability. The mental chronometry is the use of response time in perceptual-motor tasks to infer the content, duration, and temporal sequencing of cognitive operations. Aim of Study: To validate the mental chronometry test as a measure to evaluate the mental imagery capacity (from both the first-person perspective and the third-person perspective) in normal population (aged 17-35). Methods:

This honours project will include an in-depth review of literature and quantitative analysis of a data set to be collected. The data set to be collected will be combined with a set of already collected data with about 35 participants recruited.

This study consisted of a series of questionnaires, including: the Movement Imagery Questionnaire-Chinese version (MIQ-C); the Vividness of Visual Imagery Questionnaire-Chinese version (VVIQ-C); Self-rating of vividness; the Vividness of Motor Imagery Questionnaire (VMIQ); and the Kinesthetic and Visual Imagery Questionnaire-20 (KVIQ-20). The mental chronometry test is a time-dependent mental imagery task that is carried out under 3 time limitation, 15s, 25s, and 45s respectively. The participants will perform the imagined knee extension action in sitting position. They will be asked to count the number of repetition verbally during the time given. Student will learn the design of the validation study, analysis of the data set and its interpretation. Student is expected to prepare a manuscript for journal submission. Ethics Application Requirements: Yes Key References: Callow, N., & Hardy, L. (2001). Types of imagery associated with sport confidence in netball players of varying skill levels. Journal

of Applied Sport Psychology, 13, 1-17. Driskell, J.E., Copper, C., & Moran, A. (1994). Does mental practice enhance performance? Journal of Applied Psychology, 79, 481-

492. Gerardin, Emmanuel, Sirigu, Angela, Lehericy, Stephane, Poline, Jean-Baptiste, Gaymard, Bertrand, Marsault, Claude, . . . Le-Bihan,

Denis. (2000). Partially overlapping neural networks for real and imagined hand movements. Cerebral Cortex, 10, 1093-1104.

Kosslyn, S.M., Behrmann, M., & Jeannerod, M. (1995). The cognitive neuroscience of mental imagery. Neuropsychologia, 33, 1335-1344.

Kosslyn, S.M., Ganis, G., & Thompson, W.L. (2001). Neural foundations of imagery. Nature Reviews Neuroscience, 2, 635-642. Liu, K.P.Y., Chan, C.C.H., Lee, T.M.C., & Hui-Chan, C.W.Y. (2004). Mental Imagery for Promoting Relearning for People After Stroke:

A Randomized Controlled Trial. Archives of Physical Medicine and Rehabilitation, 85, 1403-1408.

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Liu, K.P.Y., Chan, C.C.H., Wong, R.S.M., Kwan, I.W.L., Yau, C.S.F., Li, L.S.W., & Lee, T.M.C. (2009). A randomized controlled trial of mental imagery augment generalization of learning in acute poststroke patients. Stroke, 40, 2222-2225.

Ryan, E.D., & Simons, J. (1981). Cognitive demand, imagery, and frequency of mental rehearsal as factors influencing acquisition of motor skills. Journal of Sport Psychology, 3, 35-45.

Wolbers, Thomas, Weiller, C, & Buechel, C. (2003). Contralateral coding of imagined body parts in the superior parietal lobe. Cerebral Cortex, 13, 392-399.

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Title of Project: A Cluster Randomised Controlled Trial of a School-based Physical Activity Intervention in At-risk Communities: The Adolescent Motivation in Physical EDucation (AMPED) Program Supervisor: Chris Lonsdale Email: [email protected] Co-supervisor: Morwenna Kirwan, Email: [email protected] Co-supervisor: Emma George Email: [email protected] Campus/s project is offered and conducted: Campbelltown or Penrith Background (200 words): This project is a large randomised trial of a school-based intervention that is designed to promote physical activity in adolescents. Students who are interested in physical activity promotion and/or the effects of physical activity on a variety of outcomes (e.g., mental health, academic performance) will have the opportunity to discuss their ideas with the research team and decide on a specific topic to investigate during their honours year. Aim of Study: To be determined based on student interest. Methods: To be determined based on student interest. Possible sources of data that will be collected in the larger project include:

1. Physical activity measured via accelerometer data. 2. Questionnaires. 3. Interviews. 4. Video observation of physical education lessons. 5. Support website usage by teachers involved in the intervention.

Ethics Application Requirements: None, ethical approval already obtained. Key References: Aelterman, N., et al. (2013). Development and evaluation of a training on need-supportive teaching in physical education: Qualitative and quantitative findings. Teaching and Teacher Education, 29, 64-75. Lonsdale, C., et al. (2013). A systematic review and meta-analysis of interventions designed to increase moderate-to-vigorous physical activity in school physical education lessons. Preventive Medicine, 152-161.

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Title of Project: Quantification of training loads and fatigue during training in AFL and NRL players Supervisor: Dr Ric Lovell Email: [email protected] Co-supervisor: To be confirmed Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): In elite-level AFL, player work-load can be quantified using data derived from various sources including heart-rate (HR), rate of perceived exertion (RPE), and global positioning systems (GPS). Furthermore, GPS technology can be used to monitor athlete motion during training in open-field environments and also during competitive match-play in AFL. As such, external work-load data from GPS can be used collectively to periodise training, and to implement training drills that are specific to the movement demands of the game. However, the use of velocity bands to characterise match-demands is a technique that might be insensitive to some high-intensity activities, which may cause transient fatigue through neuromuscular or metabolic pathways. High-intensity actions such as collisions, accelerations, decelerations, unorthodox running and turns often occur at velocities below high speed running thresholds (typically 15 km·h-1), but these activities are metabolically taxing (Drust et al, 2007). The advancement of micro-sensor technology within the GPS units now enables practitioners in team sports settings to measure the frequency and magnitude of instantaneous accelerations in the anterior-posterior, medio-lateral, and longitudinal planes. The tri-axial accelerometer is typically used for estimates of physical activity and energy expenditure, therefore powerful movements and accelerations, which are absent from traditional time-motion techniques, can now be quantified during match-play in field-based settings. Recently, there has been plethora of research into the physiological demands and responses to a variety of training drills (For a review see Hill-Haas et al., 2011), with the aim of combining technical and tactical skills with physical conditioning. These studies have assessed the impact of modifying drill characteristics such as player numbers, pitch dimensions, drill conditions and coach encouragement. However, there is a dearth of information on the variation in both internal and external loads on players when performing such practices both within and between training sessions. Moreover, the demands induced by training drills have not expressed in relation to the players typical physical requirements from competitive AFL games. Since in other football codes, match-play comprises more than 25% of the weekly training dose, it is important to ensure training drills are prescribed in an individualised fashion, so that training can be optimized and so that non-functional over-reaching can be avoided. Aim of Study: Therefore, the aim of this project is to: 1) assess the variability in both the internal and external load parameters of elite AFL players in training drills; and 2) to express these response in relation to individual match performances. Methods: Players from a local elite AFL squad will wear be harnessed with a 5 Hz GPS (MinimaxX, Catapult, Australia) unit during competitive league fixtures. Locomotor activities in arbitrary velocity bands, and tri-axial accelerometer data (Player Load - PL) are derived from the GPS system. Whilst accelerometer measures in sport and exercise settings are in their infancy, both the within- and between-unit variability is low (~1 % CV; Boyd et al., 2011) and they provide a more rigorous assessment of the players mechanical stress than the traditional method of time-motion data in arbitrary velocity categories. During games players will also wear heart rate monitors to determine internal work-loads and session RPE will be collected individually

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30 mins after each fixture. The same procedures will be adopted in training sessions. Here players will perform a range of pre-selected drills and will be monitored as above. Players will repeat these drills both on different days, and within the same training session to determine variability of responses. The drills will be modified by pitch size, player numbers and game conditions and responses to these will be expressed as individuals game-equivalent. Ethics Application Requirements: A minor amendment will be submitted for an existing project, which has received approval from both the Human Research Ethics Committee (H9807) and the Biosafety and Radiation Safety Committee (B9815). Key References: Hill-Haas et al. Physiology of small-sided games training in football: a systematic review. Sports Med (2011) vol. 41 (3) pp. 199-220. Drust et al. Future perspectives in the evaluation of the physiological demands of soccer. Sports Med (2007) vol. 37 (9) pp. 783-805. Boyd, L.J., Ball, K. and Aughey, R.J., In Press, The reliability of MinimaxX accelerometers for measuring physical activity in Australian football. International Journal of Sports Physiology and Performance.

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Title of Project: Individualisation of work-rate during match-play in AFL players Supervisor: Dr Ric Lovell Email: [email protected] Co-supervisor: To be confirmed Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): Match analysis techniques have been used by researchers to study the movement patterns of team sport players for a number of years [1,2]. The aim of earlier studies [2,3] was generally to describe the types of movements that players were exposed to in order to use that information for the development of game-specific training programs, because at the time very little objective data existed. In many previous research studies the movement patterns of players have been split into categories based on arbitrary speed thresholds, such as standing (0 – 0.7 km.h-1), walking (0.7 – 7.2 km.h-1), jogging (7.2 – 14.4 km.h-1), running, (14.4 – 19.8 km.h-1), high-speed running (19.8 – 25.2 km.h-1), and sprinting (> 25.2 km.h-1) [4,5]. However, modern match analysis systems should provide applied practitioners with information on the physical/physiological ‘stress’ imposed on the player in order to monitor the overall physical ‘dose’ of playing, rather than providing them with a movement category-based view of distances covered based on arbitrary speed thresholds. The alternative to a movement category-based method of describing the match physical performance of professional team sports players is one based on individualised and objective speed and intensity thresholds [6]. Abt and Lovell [6, 7] recently described the use of the second ventilatory threshold (VT2 – also called the respiratory compensation point) to delimit a speed threshold above which players were exercising at ‘high-intensity’. The importance of this is that the distance covered at high-intensity has been reported to be the most appropriate measure of match physical performance [1]. The advantages of such a system are that: (1) a description of the match physical demands is based on a players own physiological power or capacity. This ensures that intensity descriptions such as ‘high-intensity’ are valid for an individual player; (2) a measure of physical ‘dose’ can be calculated if the other physiological thresholds/capacities are also measured (i.e maximal aerobic speed, peak sprinting speed). Aim of Study: The aims of the present study are to: (1) demonstrate a new approach to describing the match physical performance of elite AFL players; and (2) examine the match-to-match reliability of this new approach compared to the existing movement category-based method. Methods: Players from a local elite AFL squad will wear be harnessed with a 5 Hz GPS (MinimaxX, Catapult, Australia) unit during competitive league fixtures. Locomotor activities will be reported in both arbitrary velocity bands, and also using player dependent velocity thresholds. To determine the individualised thresholds, data collected from routine physical screening batteries will be used. These methods will be compared and the match-to-match variability in the work rate will also be assessed. Ethics Application Requirements: This project has already received approval from both the Human Research Ethics Committee (H9807) and the Biosafety and Radiation Safety Committee (B9815). Key References: 1. Mohr M, Krustrup P and Bangsbo J. Match performance of high-standard soccer players with special reference to development of fatigue. J Sports Sci 2003; 21:519-28. 2. Reilly T and Thomas V. A motion analysis of work-rate in different positional roles in professional football match-play. J Hum Movement Stud 1976; 2:87-97.

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3. Withers RT, Maricic Z, Wasilewski S et al. Match analysis of Australian professional soccer players. J Hum Movement Stud 1982; (8):159-76. 4. Rampinini E, Bishop D, Marcora SM et al. Validity of simple field tests as indicators of match-related physical performance in top-level professional soccer players. Int J Sports Med 2007; 28(3):228-35. 5. Rampinini E, Coutts A, Castagna C et al. Variation in top level soccer match performance. Int J Sports Med 2007; 28(12):1018-24. 6. Abt G and Lovell R. The use of individualized speed and intensity thresholds for determining the distance run at high-intensity in professional soccer. J Sports Sci 2009; 27(9):893-98. 7. Lovell, R., and Abt, G. (2013). Individualization of Time-Motion Analysis: A case-cohort example. Int J Sports Phys Perf, 8, 456-458.

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Title of Project: The effect of a soccer half-time re-warm-up upon thermoregulation and performance. Supervisor: Dr Ric Lovell Email: [email protected] Co-supervisor: To be confirmed Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): Research has challenged the typically passive half-time (HT) interval in soccer (Mohr at al., 2004; Lovell et al., 2013a, 2013b; Weston et al., 2011). During this period muscle temperature has been shown to decrease by 1.5-2.0 °C (Lovell et al., 2013; Mohr et al., 2004) which may result in impaired muscular performance at the start of the second-half. In support of this hypothesis, research studies administering active re-warm-ups in the latter 5-7 min of the HT interval have attenuated the decline in muscle temperature, and the associated decline in high-intensity tasks such as sprinting, jumping and dynamic strength (Mohr et al., 2004; Lovell et al., 2013). Interestingly, in a recent survey of elite soccer sports scientists and fitness coaches’ (Towlson et al, 2013), many reported that only 2-3 minutes might be available for re-warming type activities. Hence there is a requirement to optimize current practices to ensure players are adequately prepared for competition. It is also presently unclear whether half-time strategies impact on technical performance. Aim of Study: The aim of the study is to determine the impact of half-time re-warm-ups on thermoregulation and physical and technical performance, Methods: 10 amateur soccer players will perform three experimental trials in a randomized cross-over fashion. Players will perform the SAFT90 soccer match simulation (see Lovell et al., 2013). At 15-minute intervals the players will perform the Loughborough Passing Test (see Ali, 2007) together with assessments lower-limb power and sprint performance. Throughout the protocol a number of thermoregulatory and physiological measures will also be taken. During the 15-min half-time period the players will either undertake a control condition (seated rest) or in the final 3-mins of half-time perform a continuous or intermittent re-warm-up matched for total work. Ethics Application Requirements: The HREC application will be submitted by November 2013 Key References:

1. Weston M, Batterham A, Castagna C, et al. Reduction in physical match performance at the start of the second half in elite soccer referees and players. Int J Sports Phys Perf 2011a; 6(2): 174-82.

2. Mohr M, Krustrup P, Nybo L, et al. Muscle temperature and sprint performance during soccer matches – beneficial effect of re-warm-up at half-time. Scand J Med Sci Sports 2004; 14: 156-162.

3. Lovell, R., Midgley, A., Barrett, S., Carter, D., Small, K. (2013a). Effects of different half-time strategies on second half soccer-specific speed, power and dynamic strength. Scandinavian Journal of Medicine and Science in Sport, 23(1), 105-113.

4. Ali, A., Williams, C., Hulse, M., Strudwick, A., Reddin, J., Howarth, L., Eldred, J., et al. (2007). Reliability and validity of two tests of soccer skill. Journal of Sports Sciences, 25(13), 1461–1470.

5. Lovell, R., Barrett, S., Portas, M., and Weston, M. (2013b). Re-examination of the post half-time reduction in soccer work-rate. Journal of Science and Medicine in Sports, 16(3), 250-254.

6. Towlson, C., Midgley, A.W., and LOVELL, R (2013). Warm-up strategies of professional soccer players: practitioners' perspectives. Journal of Sports Sciences: doi: 10.1080/02640414.2013.792946 [Epub ahead of print].

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Title of Project: Investigating the interactions of the Wnt Pathway and Docetaxel – Uncovering prostate cancer signalling Supervisor: Simon Mahoney Email: [email protected] Co-supervisor: TBA depending on project Email: Campus/s project is offered and conducted: Campbelltown Background: Prostatic adenocarcinoma is the second most commonly diagnosed malignancy in men and is the most common cause of death in men in many western countries. Similar to other cancers, prostate cancer has numerous clinical states ranging from a hormone-naïve clinically localised primary tumour to lethal androgen-independent metastases. The mainstay of primary prostate treatment options is combined androgen ablation and taxane therapy; while this approach is curative in early stage cases late stage treatment often results in refractory disease development, with late stage prostate cancer currently considered incurable. The most common taxane in use is the compound, Docetaxel, and is an effective by preventing cells from progressing into the replication phase of the cell cycle. The Wnt family of secreted ligands operates through multiple receptors, to modulate integrated signalling pathways in embryonic development, in adults and in prostate cancer progression. Recently, methylation of the Wnt inhibitory sFRP proteins has been suggested as a marker of progressing carcinoma, with a resulting poor prognosis. Of the sFRP proteins, sFRP4 has also been indicated to have antiangiogenic and pro-apoptotic properties in a wide variety of cells while sFRP4 also appears to affect androgen-dependent and androgen-independent prostate cancer. This project seeks to understand the potential interaction between sFRP proteins and modern chemotherapeutic treatment in prostate cancer cells. It seeks to investigate whether the Wnt/sFRP methylation status reflects tumour progression and whether blocking the Wnt pathway increases treatment effectiveness. Phenoxodiol is a synthetic isoflavone molecule first isolated from soy beans and currently undergoing Phase Ib/IIa clinical trials for the treatment of late stage prostate cancer. Phenoxodiol has been shown to elicit cytotoxic effects against a broad range of human cancers however, regardless of progression in clinical trials, the primary cellular signalling target or targets of phenoxodiol remain elusive and multiple studies covering various cancer cell types have detected different methods of action. The Mahoney lab has investigated the interaction of; Phenoxodiol as a novel therapeutic agent, Docetaxel as a conventional treatment and Wnt pathway inhibition previously and I hope to expand the scope of understanding in this area further. Aim of Study: The major aim of this research is to investigate the signalling pathways in early and late stage cancer models, to determine the most effective treatment course using conventional and novel chemotherapeutic agents. While the project will use prostate cancer models it will incorporate as necessary analysis of breast, ovarian, melanoma, kidney and muscle tissue models. The specific aims of individual pathways are;

1. Investigating the methylation status of Wnt pathway molecules in prostate cancer 2. Investigating the interaction of sFRP4 with Docetaxel treated cells 3. Measuring apoptosis within models of combined treatments 4. Investigating the Wnt pathway interactions with Docetaxel and Phenxodiol treatment 5. Silencing Wnt pathways to mimic effects of SFRP family

Methods: The major methods and techniques employed include, cell and tissue culture techniques (bacteria, yeast, eukaryotic cells), cell proliferation, apoptotic studies, DNA/RNA/Protein extraction, flow cytometry, fluorescent activity analysis, transformation, transfection, PCR, siRNA silencing, SDS-PAGE, agarose gels, western blotting, immunoprecipitation. Reagents and infrastructure as well as expertise with techniques is available in the from collaborators (including Dr Sabine Piller, Dr Gabriel Perrone, Associate Professor Qihan Dong).

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Ethics Application Requirements: Experiments to be performed using immortalised cell lines and will not require primary samples. Key References: http://www.ncbi.nlm.nih.gov/pubmed/23039795, http://www.ncbi.nlm.nih.gov/pubmed/23035359, http://www.ncbi.nlm.nih.gov/pubmed/20056841, http://www.ncbi.nlm.nih.gov/pubmed/20952759, http://www.ncbi.nlm.nih.gov/pubmed/21344486, http://www.ncbi.nlm.nih.gov/pubmed/17476687

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Title of Project: The reliability of voluntary activation measures within a cycling based measurement model Supervisor: Dr. Paul Marshall Email: [email protected] Co-supervisor: Dr. Jason Siegler Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Voluntary activation (VA) of a muscle is the proportion of maximal possible force that is produced during a voluntary contraction. A progressive decline in VA during exercise is the classical definition of central nervous system fatigue. VA is typically estimated using the twitch interpolation method. Twitch interpolation involves application of a supramaximal electrical stimulus to the peripheral nerve or belly of a muscle during an isometric voluntary contraction. During a maximal voluntary contraction the presence of a superimposed twitch produced by stimulation demonstrates that the force output produced by muscle is less than maximal, and suggests that either the stimulated motor units are not all recruited or they are discharging at suboptimal rates. VA is often measured to express central activation change during fatiguing exercise protocols. Recently, the two supervisors’ of this application led a study that examined reductions in maximal force output during a repeated sprint cycling session. A novel method was used to measure force, based on a fixed position within the normal cycling stance. What was not clear from this study is whether or not declines in maximal force are associated with mechanisms proximal or distal to the neuromuscular junction. Examination of voluntary activation changes may provide insight into the fatigue mechanisms of cycling, but first a method must be developed that is specific to the cycling position. Aim of Study: To examine the within and between-session reliability of a voluntary activation method tailored to an on-the-bike cycling posture. Methods: Twitch interpolation will be applied to the femoral nerve, and direct muscle stimulation to the gluteus maximus on the target limb to elicit a gross lower limb twitch in the custom set-up designed by Dr. Marshall and Dr. Siegler. Within and between-session reliability of VA measures will be calculated, in addition to establishing the relationship between interpolated twitch force and voluntary force. The student’s thesis will be required to focus on methodology development for eliciting a twitch in the cycling posture prior to performing reliability trials. It is likely that a preliminary sample size of 10 participants (across multiple days) can be tested for feasibility of this project within an honours year. This will be invaluable research for expansion of ongoing experimental studies into protocols with greater ecological validity. Ethics Application Requirements: Will need to be submitted prior to end of year if students sign onto project. Key References: Siegler, J.C. Marshall, PWM. Raftry, S. Brooks, C. Dowswell, B. Romero, R. Green, S. (2013). The differential effect of metabolic alkalosis on maximum force and rate of force development during repeated, high-intensity cycling, J Appl Physiol in 2nd revision. Merton P. Voluntary strength and fatigue. J Physiol 1954;123:553-64. Gandevia SC, Enoka RM, McComas AJ, et al. eds. Fatigue: neural and muscular mechanisms. New York: Plenum Press, 1995.

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Title of Project: Does lifting heavy weight matter if volume is the same? Supervisor: Dr. Paul Marshall Email: [email protected] Co-supervisor: Dr. Jason Siegler Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Of interest for strength and conditioning researchers and coaches is whether or not different types of exercise program are likely to elicit similar or different nervous system and muscle adaptation. Of particular interest is whether the manipulation of training intensity, defined as the percentage of a 1-repetition-maximum (1-RM) strength test prescribed for training (e.g. 60%, 80%), elicits similar or different changes in outcome measures of strength and underlying nervous system adaptation. It has recently been suggested that as long as the same total volume of exercise is performed, similar hypertrophic responses will be observed regardless of how training intensity is manipulated. However, training programs utilizing higher relative intensities seem more likely to induce greater strength changes. The time course of strength and neural adaptation throughout a training program where intensity is manipulated, but volume kept constant, has not been examined in resistance trained individuals. Aim of Study: To perform a short-term study (6 weeks) comparing strength and nervous system outcomes between two resistance training programs, where volume is equal but intensity of load is manipulated. Methods: More than one student may work on this project, as different aspects of adaptation may be added for each student. Primary dependent variables measured before and after training will be maximal ankle plantarflexion strength, and measures of neural drive and spinal reflex excitability (V-wave and H-reflex). Ethics Application Requirements: The core project has ethical approval (H10077) to the end of 2014, although a minor amendment will be required depending on number of students involved, and for the use of peripheral nerve stimulation. Key References: Aagaard P, Simonsen E, Andersen J, Magnusson P, Dyhre-Poulsen P (2002) Increased rate of force development and neural drive of human skeletal muscle following resistance training. J Appl Physiol 93:1318-1326 Mitchell CJ, Churchward-Venne TA, West DWD, Burd NA, Breen L, Baker SK, Phillips SM (2012) Resistance exercise load does not determine training-mediated hypertrophic gains in young men. J Appl Physiol 113:71-77

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Title of Project: Postural control of the trunk muscles and prolonged standing Supervisor: Dr. Paul Marshall Email: [email protected] Co-supervisor: Dr. Siobhan Scharbrun Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Low back pain (LBP) is a significant health and economic burden around the world. Occupations that involve prolonged standing have a strong association with LBP development. Experimental studies have observed that 2-h of prolonged standing will elicit clinically relevant pain reporting in the low back for between 40-60% of young, previously asymptomatic individuals. Postural control of the trunk appears altered in pain reporters prior to prolonged standing. The relationship between anticipatory and compensatory postural adjustments (APAs and CPAs) of the trunk in response to a rapid limb perturbation has not been compared between people who do, and do not report pain in the low back during 2-h prolonged standing. Further examination of underlying mechanisms that explain altered postural control and subsequent low back pain reporting during prolonged standing may help the design of targeted interventions to address this costly problem. Aim of Study: The aims of this study are to determine: 1) whether trunk muscle APAs and CPAs and measures of trunk stability can be altered following 2-h prolonged standing, and 2) whether APAs and CPAs and the regulation of trunk stability would be different between pain and non-pain reporters prior to or after prolonged standing. Methods: Based on pilot data from the primary supervisor performing a preliminary examination of APAs and CPAs in people who do and do not report LBP during 2-h standing, 20 healthy young people with no history of back pain should be recruited to identify n=10 who do and n=10 who do not report pain in the low back during 2-h standing. Surface electromyography techniques in addition to examination of center-of-pressure changes using the Kistler force platform will be the primary methods of data collection. Ethics Application Requirements: Will need to be submitted prior to end of year if students sign onto project. Key References: Tissot F, Messing K, Stock S (2009) Studying the relationship between low back pain and working postures among those who stand and those who sit most of the working day. Ergonomics 52:1402 - 1418 Marshall PWM, Patel H, Callaghan JP (2011) Gluteus medius strength, endurance, and coactivation in the development of low back pain during prolonged standing. Human Movement Science 30:63-73 Raftry, SM. Marshall, PWM (2012) Does a ‘tight’ hamstring predict low back pain reporting during prolonged standing? J Electromyogr Kinesiol, 22: 407-411. (lead author UWS Honours Research Student, 2010)

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Title of Project: Validation of commercially available wrist-worn physical activity monitors in free-living environments. Supervisor: Associate Professor Dafna Merom Email: [email protected] Co-supervisor: Dr Morwenna Kirwan Email: [email protected] Co-supervisor: Mr Andrew Webber Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): The peril of prolonged sitting irrespective of regular exercise highlights the need to measure physical activities at the lower range of energy expenditure. Unfortunately self-report questionnaires suffer from large overestimation errors, particularly of activities at moderate intensity or below. It has been shown that people recall vigorous intensity or purposeful exercise more accurately than time spent in incidental light intensity activity. This is attributed to the low salience these light intensity activities have. Waist worn accelerometers provide a robust method for describing major differences between sitting time as well as time spent in simple dynamic physical activities such as walking and running. However, the static elements of many lifestyle activities with low ambulation (i.e., household chores) is likely to be underestimated by these devices, as are complex physical activities with low ambulation such as tai-chi, yoga and resistance training. Advancement of physical activity measurement depends on developing new approaches to measure activity at a wide range of intensities and those with complex movement patterns. Aim of Study: To validate the use of commercially available wrist worn physical activity monitors to estimate step count and time spent in different intensities of physical activity in a free-living environments. Methods: Participants will be asked to wear three wrist-worn physical activity monitoring devices (Fitbit Flex, Jawbone Up, ActiGraph GT3X) and a second ActiGraph accelerometer (worn on the hip) simultaneously and continuously for a period of 5 days whilst they go about their daily activities. Participants will be required to keep an activity log over the period of wear. The log will ask for participants to recall the types of activities they engaged in across the day, the number of minutes they engaged in each of the activities and a rate of perceived exertion value to indicate perceived intensity (having previously been trained in use of the scale). On at least one occasion, the participant will be observed for a specified period whilst the investigator logs participant’s activities. Ethics Application Requirements: Ethical approval will be required. Key References: Ainsworth, B. E., Haskell, W. L., Whitt, M. C., Irwin, M. L., Swartz, A. M., Strath, S. J., . . . Leon, A. S. (2000).

Compendium of physical activities: An update of activity codes and MET intensities. Medicine and Science in Sports and Exercise, 32(9 SUPPL), S498-S504.

Baranowski, T., Validity and reliability of self-report measures of physical activity: an information porocesing perspective. Research Quarterly for Exercise & Sport. 1988;59(4):314-27

Matthews, C.E., Caliberation of accelerometer output for adults. Medecine & Science in Sports & Exercise. 2005;37(11(Suppl)):S512-S22.

Yore, M.M, Ham, S.A., Ainsworth B,E,. et al. Reliability and validity of the instrument used in BRFSS to assess physical activity. Med. Sci. Sports Exerc. 2007;39(8):1267-74.

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Title of Project: Older adults’ perceived intensity during dance and its relation to objective measured intensity level by accelerometers and 6-minute walking test (6MWT). Supervisor: Associate Professor Dafna Merom Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Participation in regular physical activity/exercise is a vital component of healthy aging. For general health older adults are advised to engage in 30 minutes of at least moderate-intensity activity on most days of the week. However, due to heterogeneity in aerobic capacity in old age activities which are classified as moderate-intensity in absolute term may be vigorous for some elderly or light-intensity for others. Activity monitors such as accelerometer provide robust methods to classify individuals by according the time spent in a range of intensity levels, however, their performance while measuring complex stepping, such as in dance or taichi is in doubt. These types of activity are highly recommended to maintain balance and are generally classified as moderate-intensity in absolute term but there has not been any formal study, which assess activity intensity performed during balance –enhancing classes and whether these dynamic activities would confer enough of aerobic challenge. Aim of Study: This project is aimed to compare the Rate of Perceived Exertion (RPE) during dance classes to accelerometer intensity levels set at a cut point equivalent to moderate-intensity walking (MET of 3.7) for older adults. Second, the association between RPE and accelerometer time spent in moderate-intensity activity during the class will be compared to individual’s performance on a 6-minute walking test (6MWT) to assess dance relative intensity from predicted cardiovascular fitness. Methods: The trial will be conducted within a randomized controlled trial aimed to compare the effects of walking and dancing on physiological and cognitive performance in old age. Participants recruited to the study undergo a battery of testing including the 6MWT. The student who selects this project will join the research team and will learn to apply the 6MWT during baseline. Then follow these participants to their dance classes and collect data from accelerometer worn on the waist and conduct periodical assessments of RPE using Borg scale. It is required that data from at least 30 participants will be analyzed, which will take about 3 months. Outcome of this study will help to better clarify the effort level associate with complex activities such as dance and whether these should be recommended as moderate-intensity beyond or bellow. Ethics Application Requirements: Ethical approval will not be required. Key References: Matthews, C.E., Caliberation of accelerometer output for adults. Medecine & Science in Sports & Exercise.

2005;37(11(Suppl)):S512-S22. Ainsworth, B. E., Haskell, W. L., Whitt, M. C., Irwin, M. L., Swartz, A. M., Strath, S. J., . . . Leon, A. S. (2000).

Compendium of physical activities: An update of activity codes and MET intensities. Medicine and Science in Sports and Exercise, 32(9 SUPPL), S498-S504.

Starth, S. J., Pfeiffer, K. A., & Whitt-Glover, M. C. (2012). Accelerometer use with childre,older adults, and adults with functional limitations. Medecine & Science in Sports & Exercise, 44, S77-S85.

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Title of Project: Testing system-based approach to prevent weight gain in GPs’ clinics – a pilot trail Supervisor: Associate Professor Dafna Merom Email: [email protected] Co-supervisor: Dr. Morwenna Kirwan Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Australia’s health care system succeeded in reducing the burden of cardiovascular diseases (CVD) largely due to systematic detection and treatment of high blood pressure, high blood lipids and smoking. Much of this gain may be diminished unless CVD lifestyle risk factors, such as physical inactivity and diet, are not addressed systematically. GPs have population-wide access to individuals of all ages and can support effective national interventions by targeting individuals, who at the end need to make the healthy choice. However, to realize their attributed influence there must be easy and quick procedures of detection and “treatment” that can fit within a busy and time-constrained clinic. Motion sensors provide a robust method for describing major differences between active and sedentary adults based on steps (pedometers) or activity counts (accelerometers). Counting steps with pedometers at a population level has enabled epidemiologists to calculate normative population indices and translate steps/day to public health recommendations. Further, advances in technology now permit quick interpretations of activity motion output and their price becomes more sensible for wider use. Aim of Study: This project is aimed to pilot ambulatory diagnostic lab linked to GPs computer and to compare clients’ “acceptability” and compliance with ambulatory measurements in two modes of recruitment: active and passive over defined time period. Methods: The trial will be conducted in two volunteering GP clinics in Southwest Sydney region, which is known for its high prevalence of obesity and diabetes. During first 2 weeks all patients admitted to the clinic will be asked by the GP to measure their ambulatory activity by wearing step-counters (FitBit or pedometers), and to record /download the data in a clinic website. Physician letter will be then sent to patients to inform their position according to population norms. Patients who are highly inactive will be invited to receive further assistant to improve their activity ambulation. Students who select this project will be based in GP clinics for four weeks and will collect the data, assess clients cooperation, provide clients with activity monitors and generate the prototype letter to be used as feedback. One student will evaluate up-take and population profile when GPs addressed the clients and one student will evaluate the up-take when ambulatory lab is advertise in the clinic’s notice board. Ethics Application Requirements: Ethical approval will be required. Key References: AIHW 2003 Are All Australian’s Gaining Weight? Differentials in overweight and obesity among adults

1989-90 to 2001. Canberra: Australian Institute of Health and Welfare Eakin EG, Smith BJ, Bauman AE.Evaluating the population health impact of physical activity interventions

in primary care – are we asking the right questions? Journal of Physical activity and Health 2005;2:197

Richardson CR, Newton TL, Abraham, JJ, Sen A, et al A meta-analysis of pedometer-based walking interventions and weight loss Anals of Familiy Medicine 2008;6:69

21. Tudo-Loke C, Craig CL, Brown WJ et al. How many steps/day are enough? For adults International Journal of Behavioral nutrition and Physical Activity 2011;8:79

22. Tudo-Loke C ,Craig CL, Aoyagi Y, et al How many steps/day are enough? For Older adults and special populations International Journal of Behavioral Nutrition and Physical activity 2011;8:80

23.Tudor-Loke, Basset DRJr, RutherfordWJ et al. BMI-reference cut points for pedometer-determined steps per day in adults Journal of Pysical Activity and Health 2008 ;5 (Suppl1):S126

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Title of Project: Validation of commercially available wrist worn physical activity monitors in controlled environments. Supervisor: Associate Professor Dafna Merom Email: [email protected] Co-supervisor: Dr Morwenna Kirwan Email: [email protected] Co-supervisor: Mr Andrew Webber Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): An inactive lifestyle is recognised as the fourth leading risk factor of the total burden of disease globally. Physical activity is a complex behaviour defined as any bodily movement resulting in energy expenditure. Self-report questionnaires are the most common practical methods for assessing physical activity in large populations. However these questionnaires suffer from large overestimation errors due to difficulties to recall activities, particularly those at lower intensities. Waist worn accelerometers provide a robust method for describing major differences between sedentary time as well as time spent in simple dynamic physical activities such as walking and running. However, the static elements of many lifestyle activities with low ambulation (i.e., household chores, cooking or window cleaning) are not quantified accurately. Commercially available wrist worn devices in combination with waist worn accelerometers may produce a more accurate picture of lifestyle physical activity. Wrist worn devices are now available at affordable prices (~$100) and may be used in large population samples, but the cut-points used by companies to provide physical activity feedback are not disclosed and no scientific study has yet to validate these devices against traditional energy expenditure measures. Aim of Study: To validate the use of commercially available wrist worn physical activity monitors to estimate step count and time spent in different intensities of physical activity in a controlled environment. Methods: Participants will be asked to wear a number of physical activity monitoring devices during an exercise protocol completed on a treadmill. These devices will include Fitbit Flex, Jawbone UP, ActiGraph GT3X accelerometer worn on the wrist, and a second ActiGraph accelerometer worn on the hip. Participants will be required to visit a laboratory on three separate occasions. The first visit will be a laboratory familiarisation session. The second and third visit will require participants to complete an identical treadmill protocol consisting of staged increments in intensity (~5 minutes duration), up to a point of volitional termination (once completed a certain period of time within the highest *MET range). Step count and minutes spent in different levels of intensity of physical activity (based upon MET ranges) will be collected from the physical activity devices. Expired gases will be collected during the exercise protocol to establish MET values during exercise as a basis of comparison (validation) to the physical activity devices. Heart rate and the rate of perceived exertion will also be monitored during the exercise protocol. *MET = Metabolic Equivalent (3.5mlO2/kgBW/min) Ethics Application Requirements: Ethical approval will be required. Key References: Bassett, D.R., Rowlands, A., & Trost, S.G. (2012). Calibration and validation of wearable monitors.

Medicine and Science in Sports and Exercise, 44(SUPPL. 1), S32-S38. Matthews, C.E., Caliberation of accelerometer output for adults. Medecine & Science in Sports & Exercise.

2005;37(11(Suppl)):S512-S22.

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Title of Project: To what extend a single measure of perceived physical activity status predict functional capacity, fitness levels and cognitive status. Supervisor: A/Prof Merom Dafna Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Increasing numbers of older adults are facing the challenges of healthy ageing. Regular physical activity (PA) / exercise can prevent physiological deterioration, increase cognitive functioning and prevent or ameliorate many prevalent chronic diseases that are associated with aging. Hence knowledge of physical activity status of older adults is important indicator of health. Self-report physical activity questionnaires inherit large measurement errors, particularly in the presence of normal age-related cognitive declines and are questioned for their accuracy on the ground of social acceptability bias. Further, the scoring algorithms by which these questionnaires classify older adults to levels of physical activity are based on absolute definition of intensity. However, with the heterogeneity in fitness level at old age this scoring system is questionable for the older population. Alternative simple but still accurate methods are required. Evidence exists that a person’s self-perceived degree of fitness, and not just measured physical activity energy expenditure by questionnaire, is an important predictor of cardiovascular mortality and even performed better compared to assessment by questionnaires. This was based on a single study and also it is unknown whether perception of physical activity or fitness is a good predictor of other dimension of fitness such as balance, reaction time, leg strength or gait pace which are important component of falls risk. Aim of Study: to assess the predictive validity of a single question of self-perceived physical activity in old age. Methods: There is a possibility to engage two students in this project. The students will first review the literature on the challenges of physical activity assessments in old age as well as the literature on the predictive value of self-perception against clinical health outcome (e.g., example of the predictive value of the widely used perceived health status question) in order to make the case. Second, the analyses will be done on data already collected from two randomised controlled trials currently managed by the supervisor. One student will analyse data from 535 older adults who gave an answer on their perceived physical activity status compared to people of similar gender and age and also assessed by short self-report physical activity questionnaires and neuromuscular fitness levels. The second student will look at data collected from 60 community dwelling older adults who also answered the self-perceived question but also conducted fitness test (6-Minute Walk Test) as well as objective measurement of accelerometer. Each student will examine the association between 1) the self-report questionnaire classification against perception using measures of agreements, and 2) between self-perception and neuromuscular fitness or aerobic fitness and activity monitors. . Ethics Application Requirements: No need Key References:

1. Merom D, Cumming R, Mathieu et al. Can social dancing prevent falls in older adults? A protocol of the Dance, Aging, Cognition, Economics (DAnCE) Fall Prevention Trial BMC public Health 2013

2. Lee IM et al. Relative intensity of physical activity and risk of coronary heart disease. Circulation. 2003; 107:1110-1116

3. Starth, S. et al (2012). Accelerometer use with childre,older adults, and adults with functional limitations. Medecine & Science in Sports & Exercise, 44, S77-S85

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Title of Project: Context and outcomes of home-based unsupervised exercise / physical activity programs delivered to older adults (65+): a systematic review Supervisor: A/Prof Merom Dafna Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Increasing numbers of older adults are facing the challenges of aging successfully; that is maintaining a low risk of disease and disease-related disabilities, high cognitive and physical functional capacities and engagement in social and productive activities. Regular physical activity (PA) / exercise are considered as the best “medicine” for successful aging. There is growing recognition that for greater population impact, health promotion efforts should focus on activities that can be easily integrated into daily routines (e.g., walking 1-2 utilizing strategies that can reach a large number of individuals in a cost-effective manner. At least in the US, half of older adults preferred programs undertaken at their home environment on their own .Home-based exercise programs are usually unsupervised and depends on strong motivation and discipline of participants. It is possible that their effectiveness might be compromised due to poor adherence. However, if this is not the case then such mode of delivery eliminates barriers to participation associate with transport, lack of access or costs. To date there hasn’t been any systematic assessment of the context and outcomes of such interventions and whether their effects are significant. Aim of Study: to review un-supervised physical activity/ exercise program undertaken at home and to assess their content, types of outcomes addressed and their effect size. Methods: The student will apply systematic review methodology. Before literature search a clear definition of the research question exclusion and inclusion criteria should be defined. In the next stage a literature search using broad defined key words on several data-based will be conducted. Selected and unselected papers will be documented; information from selected papers will be tabulated and prepared for analysis when appropriate. Estimation of effects will be conducted when the same outcomes are reported using the R software. Ethics Application Requirements: No Key References:

1. Merom D, Rissel C, Phongsavan P, Smith B, Brown W, Bauman A. Promoting walking with pedometer in the community. The Step by Step trial. Am. J. Prev. Med. 2007; 32(4) 290-297

2. King et al. Physical activity intervention for older adults J Gerontol Series A 2001; 56A:36-46 3. Voukelatos A, Merom D et al. The effect of walking on falls in older people: the Easy Steps to

Health randomized controlled trial study protocol. BMC Public Health. 2011;11:888

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Title of Project: Water Disinfection Using Solar Energy Supervisor: Michelle Moffitt Email: [email protected] Co-supervisor: Janusz Nowotny Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): As many as 2 million people worldwide die from waterborne diseases annually. Many of these are children under the age of 5. Development of a drinking water disinfection system for people at risk that is cheap and not reliant on chemical treatment or mechanical treatment fuelled by fossil fuels is the basis of this work. In this project, we will optimise the use of semiconducting oxides for the conversion of solar energy to chemical energy for the partial oxidation of water, resulting in the removal of hazardous microorganisms from waste water. The primary products of the partial oxidation of water are reactive oxygen species (ROS), including hydroxyl radicals, superoxide and hydrogen peroxide. These products then react with organic molecules within microorganisms, leading ultimately to their oxidation and cell death. This effect has been reported previously, however, it is necessary to optimise the efficiency of semiconductors for this purpose. Once optimised, titanium dioxide semiconductors, which are low cost, could be scaled up accordingly for use in households. Given the exclusive use of solar energy in the treatment process, this method of water purification represents an energy efficient and chemical free alternative to current water purification methods. Aim of Study: Development of oxide photocatalyst for water disinfection using solar energy. Methods: As part of this project, the student will use microbiological techniques to analyse the disinfection efficiency of a range of semiconducting oxides which will be created by the Solar Energy Technology research team. Specifically the student will monitor the removal of a range of microorganisms that are known to cause waterborne diseases. Techniques used will include cell counts and live/dead staining, in addition to some molecular analyses. Ethics Application Requirements: None Key References: NJ Sucher et al, Adv Appl Ceramics 111 (2012) 16

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Title of Project: Genes associated with toxicity in cyanobacteria Supervisor: Michelle Moffitt Email: [email protected] Co-supervisor: Oliver Morton Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Many bacteria produce small molecules during secondary metabolism that have specific biological activities. These molecules are thought to have evolved to enhance the survival of the microorganism in it’s environment. Their biological activities are of interest to humans for their pharmaceutical benefits. We are particularly interested in the way in which these chemicals are constructed by bacteria in Nature and the role of these chemicals in the functioning of the cell. Our research currently focuses on natural products produced by Australian cyanobacterial isolates. Two compounds of interest, hapalosin and welwitindolinone, have been shown to have anticancer activities. Saxitoxin, which is a neurotoxin and geosmin, which causes off taste in drinking water, are also of interest in our lab since cyanobacteria produce these compounds in our drinking water dams. We have sequenced the genomes of four of these cyanobacterial isolates. Aim of Study: To analyse gene sequences responsible for natural product biosynthesis and determine their enzymatic function or environmental regulation. Methods: The project will include some bioinformatics analysis of the genomes, as well as some real time PCR or protein expression and characterisation. Ethics Application Requirements: None Key References: D'Agostino, P. M., Wiese, M., Mihali, T. K., Moffitt, M. C., Neilan, B. A. (2010). Neurotoxic alkaloids: Saxitoxin and its analogues. Marine Drugs, 8, 2185-2211. Welker, M., Dittmann, E., von Döhren, H., Cyanobacteria as a Source of Natural Products (2012). Methods in Enzymology, 517, 23-46.

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Title of Project: The expression of myosin heavy chain isoforms in mdx skeletal muscle: a semiquantitative analysis. Supervisor: Professor John Morley Email: [email protected] Co-supervisors: Dr. Stewart Head Email: [email protected] Co-Supervisors: Dr. Sindy Kueh Email: [email protected] Campus/s project is offered and conducted: School of Medicine, Campbelltown Campus Background (200 words): Duchenne muscular dystrophy (DMD) is the second most common X-linked genetic condition that affects

approximately 1 in 3,500 live male births. The disease is caused by mutations in the dystrophin gene,

which may lead to the absence of the protein dystrophin or expression of a non-functional truncated

protein product. Duchenne muscular dystrophy is characterized by progressive muscle wasting, resulting

in muscle weakness of variable distribution and severity (Culligan et al., 1998; Emery, 1987; Emery, 1991;

Emery, 2002). In the human DMD, a reduction of myosin heavy chain (MyHC) type 2b has also been

demonstrated (Spassov et al., 2010). A reduction in the MyHC-2b and MyHC-2x expression has also been

reported in the masticatory muscles of mdx mice, a mouse model for DMD. In addition, the authors

found an increase in the number of fibers with centralized nuclei in the masseter, temporal, tongue and

soleus muscle of mdx mice when compared to control. This suggested that the mdx muscles are unequally

implicated in the development of DMD.

Myosin heavy chain is the main protein component involved in muscle contraction. The contractile

properties of skeletal muscles are largely dependent on the composition of this protein (Bottinelli et al.,

1996; Smerdu & Soukup, 2008). Several isoforms of MyHC exist in skeletal muscle: the MyHC-2b, MyHC

2x and MyHC-2a; classified as fast type and the MyHC-1; classified as slow type fibers. The expression of

the different the MyHC isoforms are regulated in a tissue- and developmental specific manner as well as

in response to various factors such as altered physiological stimuli, ageing and to various diseases

(Hartmann et al., 1999; Spassov et al., 2010).

Aim of Study: In this study, we aim to perform quantitative analysis for both gene and protein expression of MyHC-1,

MyHC 2a, 2b and 2x in four different skeletal muscles, namely the extensor digitorium longus (EDL; fast

type fiber), flexor digitorium brevis (FDB; fast type fiber), soleus (slow type fiber) and diaphragm (fast and

slow type fiber) from 5 each of mdx and littermate control mice in (i) 2-3 weeks (ii) 8-12 weeks and (iii)

>24 months old mice. Information from this study will allow a better understanding of how these muscles

adapt to dystrophic changes and the influence of the absence of dystrophin on fiber properties of these

muscles. A greater understanding of the functional role of dystrophin will assist clinical scientist develop

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a better management plan for DMD and perhaps provide boys with DMD with an improved quality of life,

until a cure is found.

Methods: Surgery Extensor digitorium longus (EDL), flexor digitorium brevis (FDB), soleus and diaphragm will be dissected

from mdx and littermate control mice, snapped frozen in liquid nitrogen and stored at -80oC until use for

experiment.

Gene expression study Total RNA will be isolated using commercially available RNA Extraction Kit (ISOLATE II RNA Micro Kit

(Bioline Australia). The Tetro cDNA Synthesis Kit (Bioline Australia) will be used to generate first strand

cDNA for real-time PCR analysis. Real time quantification for the different MyHC isoforms will be

performed using gene specific primers. The quantity of the different gene transcript for MyHC isoforms

are determined from CT values obtained during PCR. Each CT value is normalized to two endogenous

housekeeping gene (GAPDH and Actin) and the average CT value compared between the dystrophic mdx

muscle and normal littermate control muscle.

Protein expression study Tissue samples will be processed and protein extracted according to a previously published method

(Smerdu & Soukup, 2008). Protein samples are then separated using a Sodium dodecyl sulphate-

polyacrylamide (SDS- polyacrylamide) gel. The separated proteins are electrophoretically transferred

from the gel onto a nitrocellulose membrane, which will be probed for MyHC-1, MyHC 2a, 2b and 2x using

isoforms specific antibodies. Immunoreactivity will be detected using a chemiluminescent system and the

intensity of the immunoreactive bands measured. The same membrane is used for immuno-detection of

actin which will be used as housekeeping control to normalize for any variability in loading and transfer.

Statistical analysis

Statistical analysis will be performed using the Prism 5.0 software (GraphPad Software, San Diego

California USA). The obtained values for the groups are compared using a Student’s unpaired t-test. Data

are given as mean ± SEM. P < 0.05 will be considered significant.

Ethics Application Requirements: Existing Ethics A9766 Key References: Bottinelli R, Canepari M, Pellegrino MA & Reggiani C. (1996). Force-velocity properties of human skeletal muscle fibres: myosin

heavy chain isoform and temperature dependence. Journal of Physiology 495(Pt 2), 573–586. Culligan KG, Mackey AJ, Finn DM, Maguire PB & O. K. (1998). Role of dystrophin isoforms and associated proteins in muscular

dystrophy. Int J Mol Med 2. Emery AEH. (1987). Duchenne muscular dystrophy. Oxford Unversity Press New York. Emery AEH. (1991). Population frequencies of inherited neuromuscular diseases -A world survey. Neuromuscul Disord 1, 19-29. Emery AH. (2002). The muscular dystrophies. Lancet 359, 687-695.

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Hartmann N, Martrette J-M, Strazielle C & Westphal A. (1999). Dystonia musculorum mutation and myosin heavy chain

expression in skeletal and cardiac muscles. J Cellular Biochem 74, 90-98. Smerdu V & Soukup T. (2008). Demonstration of myosin heavy chain isoforms in rat and humans: the specificity of seven available

monoclonal antibodies used in immunohistochemical and immunoblotting methods. Eur J Histochem 52, 179 -190. Spassov A, Gredes T, Gedrange T, Lucke S, Morgenstern S, Pavlovic D & Kunert-Keil C. (2010). Differential expression of myosin

heavy chain isoforms in the masticatory muscles of dystrophin-deficient mice. In Eur J Orthod.

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Title of Project: Examination of the similarity between the interaction of Human THP1 monocytes with pathogenic fungi and Trichomonas vaginalis with pathogenic fungi. Supervisor: Oliver Morton Email: [email protected] Co-supervisor: Colin Stack Email: [email protected] Co-supervisor: Graham Jones Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): The cells of the innate immune system, neutrophils, macrophages and dendritic cells are important for defence against pathogenic fungi. Inhaled fungi are ingested through phagocytosis by macropahges and neutrophils in the alveoli. The fungi within the phagocytic vacuoles are usually killed but can overwhelm the immune cell if they are present in sufficient numbers. It has been suggested that disseminated fungal infection is mediated by the survival of the pathogen within phagocytic cells. The origin of resistance to phagocytic cells is thought to stem from interactions between fungi and protozoans in soils and other natural habitats. Aim of Study: The aim of this study is to establish a model system to examine the interactions between pathogenic fungi and phagocytic cells. This will involve seeing if the response of the protozoan Trichomonas vaginalis to exposure with pathogenic fungi is similar to that of human immune cells (THP1 monocytes). The phaogcytic cells will be tested against the major pathogenic fungi, e.g. Aspergillus, Fusarium, Rhizopus, Mucor, and Candida. This will lead to the development of a system where the ability of pathogenic fungi to resist the immune system can be evaluated. Methods: Maintenance and establishment of protozoan cultures, preparation of fungal cultures and spore suspensions. Using flow cytometry and fluroescenece microscopy to measure phagocytosis and cell death. Use of qPCR to measure host and pathogen gene expression. Ethics Application Requirements: None Key References: Pereira-Neves A, Benchimol M. (2007) Phagocytosis by Trichomonas vaginalis: new insights. Biol Cell. 99(2):87-101.PMID:17029588 Krappmann S. (2006) Tools to study molecular mechanisms of Aspergillus pathogenicity. Trends Microbiol.; 14(8):356-64. PMID:16806936 Chamilos G, Lionakis MS, Lewis RE, Kontoyiannis DP. (2007) Role of mini-host models in the study of medically important fungi. Lancet Infect Dis; 7(1):42-55. PMID:17182343

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Title of Project: Interactions of tear proteins for antimicrobial defence at the ocular surface Supervisor: Dr Poonam Mudgil Email: [email protected] Co-supervisors: A/P Matt Edwards, Prof John Whitehall Email: [email protected], [email protected] Campus/s project is offered and conducted: Campbelltown campus (School of Medicine) Background (200 words): Bacterial eye infections are generally treated with antibiotics. While increasing antibiotics resistance among bacterial pathogens is a big concern, use of topical antibiotics also carry the risk of systemic side effects which are particularly serious in children.1 Understanding innate host defence mechanism and augment it with natural compounds can help in proposing alternative therapies to tackle the problems associated with antibiotics. Tears act as first line of defence against ocular infections and contain antibacterial proteins which help in combating bacterial infections.2 Studies on their action alone and in combinations will help in enhancing our knowledge of innate host defence mechanism. This knowledge can be used in developing protein based treatments containing combinations of antimicrobials with different molecular mechanisms to have a broader spectrum of activity against pathogens and thereby reducing antibiotics usage. Aim of Study: This project aims to investigate the interactions of antimicrobial proteins found in tears to understand the innate defence mechanism of tears that protects the ocular surface from bacterial infections. Methods: Antibacterial effects of commercially available tear proteins will be tested against ocular pathogenic bacteria in near physiological conditions using broth dilution technique and minimum inhibitory concentrations will be determined. Checkerboard approach will be used to determine antibacterial effects of proteins in various combinations in an artificial tear medium for understanding interactions of tear proteins in providing antibacterial defence. Ethics Application Requirements: N/A Key References: 1Wallace & SteinKuller, 1998, Clinc Pediatr (Phila), 37:645 2Jett, 2006, Duanne’s Foundations of Clinical Ophthalmology, 2006, vol 2, ch 45

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Title of Project: Prevention of neurodegeneration in Alzheimer’s disease by a combination of anti-inflammatory antioxidants Supervisor: Prof. Gerald Muench Email: [email protected] Co-supervisor: Dr. Erika Gyengesi Email: [email protected] Campus/s project is offered and conducted: Campbelltown

Background (200 words):

Oxidative stress is a disturbance between the production of reactive oxygen species (ROS) such as superoxide and nitric oxide (NO) and their detoxification. Brains of patients with Alzheimer’s disease show substial oxidative damage, which can be explained by chronic inflammation, whereby activated glia are a source of ROS through the activation of NADPH oxidase and inducible nitric oxide synthase (iNOS), respectively. Antioxidants e.g. vitamin E and vitamin C, and other plant derived antioxidants work as radical scavengers and are sacrificed in the process, but they can be regenerated by other antioxidant substances such as reduced lipoic acid. These redox cycles form an 'antioxidant network' which is the main line of defense against free radicals in biological systems. ROS also act as signals for redox-sensitive transcription factors (NF-kB, AP-1). These factors control the expression of genes that detoxify ROS, regulate the immune system including the expression of multiple cytokines (1,2, 4). By supplementing the antioxidant network by an antioxidant combination including plant derived anti-oxidants and foods, we propose that one can downregulate redox-sensitive gene expression, inflammation and prevent neuronal cell death. Aim of Study:

1. To determine the potency of a variety of antioxidants and plant-derived foods to down-regulate the IFN-gamma + LPS production of free radicals (superoxide and nitric oxide) and pro-inflammatory cytokines (IL-1, IL-6 and TNF) in murine microglial cell lines.

2. To investigate how activated microglia change neuronal cell viability in a murine microglia-neuron co-culture, and which of the antioxidants or food/herb samples are able to attenuate these changes.

Methods:

For AIM 1: To determine the potency of a variety of antioxidants (alone and in combination) to down-regulate the LPS-induced production of free radicals (superoxide and nitric oxide) and pro-inflammatory cytokines (IL-1, IL-6 and TNF) in microglia: We will use our N-11 murine microglial, which responds to the combination of LPS and a second inflammatory stimulus such as IFN with the production of IL-1, TNF and NO. Activation of microglia will be monitored by NO and superoxide production, as well as TNF and IL-6 expression. The effect of the antioxidants on redox-regulated cytokine/iNOS expression will be tested with lipoic acid, vitamin E and C and selenium and the bioflavonoids / polyphenols apigenin, diosmetin and resveratrol (3), curcumin and melatonin alone and in various combinations to find the most potent “antioxidant mix”. In addition, the most potent foods from our food library will also be included (4). For AIM 2: To investigate to which degree activated microglia change neuronal cell viability, and which of the antioxidants are able to attenuate these changes: we will use “Transwell” plates to grow microglia and neurons in the same well, separated by a semi-permeable membrane. This approach has the advantage that toxic diffusible short-lived factors such as ROS will also be able to exert their neurotoxic actions. Combinations of LPS and IFN-gamma will be tested for maximal neurotoxicity and disturbance of energy production. Potent antioxidants and antioxidant combinations as well as foods (identified in AIM 1) will be tested for their neuroprotective and pro-energetic properties using the readouts below. Cell death: Cell death will be monitored by cell viability assays including MTT, Neutral Red and Alamar Blue. Glucose

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metabolism: Changes in glucose consumption and lactate production will be determined by the glucose oxidase and the LDH assay, respectively. ATP will be determined with a Bioluminescence Assay kit (Roche Diagnostics). The mitochondrial dye JC-1 will be used to distinguish between healthy and impaired mitochondria by fluorescence microscopy. Ethics Application Requirements: N/A Key References:

1) Shanmugam K et al (2008) Plant-derived polyphenols attenuate lipopolysaccharide-induced nitric oxide and tumour necrosis factor production in murine microglia and macrophages. Mol Nutr Food Res 52: 427-38.

2) Hansen E, Krautwald M, Maczurek AE, Stuchbury G, Fromm P, Steele M, Schulz O, Garcia OB, Castillo J, Körner H, Münch G. A versatile high throughput screening system for the simultaneous identification of anti-inflammatory and neuroprotective compounds. J Alzheimers Dis. 2010;19(2):451-64. doi: 10.3233/JAD-2010-1233.

3) Nguyen NT, Ooi L, Piller SC, Münch G Proenergetic effects of resveratrol in the murine neuronal cell line Neuro2a. Mol Nutr Food Res. 2013 Aug 12. doi: 10.1002/mnfr.201300145. [Epub ahead of print]

4) Gunawardena D, Shanmugam K, Low M, Bennett L, Govindaraghavan S, Head R, Ooi L, Münch G. Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods. Eur J Nutr. 2013 May 8. [Epub ahead of print]

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Title of Project: Consequences of chronic neuroinflammation on the brain: implications on Alzheimer's disease Supervisor: Gerald Muench Email: [email protected] Co-supervisor: Erika Gyengesi Email: [email protected] Co-supervisor: Tim-Stait-Gardner Email: [email protected] Co-supervisor: William Price Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Epidemiological evidence shows that plant-derived foods with anti-inflammatory and anti-oxidant potential protect against Alzheimer’s disease (AD), but it is not clear which compounds are responsible for this positive effect. Activated, cytokine-overexpressing microglia are near-universal components of Aβ plaques at early and mid stages during the progression of AD, and only decline in end-stage, dense core plaques. Activated microglia show close associations with tangle-bearing cholinergic neurons in AD. However, transgenic animal models of AD, which overexpressing mutant forms of presenilin, tau and amyloid precursor protein do not show the same variety of pro-inflammatory markers as human AD patients and develop a much weaker neuroinflammatory phenotype. To establish an animal model in which specific food compounds can be tested, we will use transgenic mice, which show chronic brain inflammation and develop progressive neurological deficits. We will monitor changes in their behavior, including a decline in cognitive functions. We will also investigate the underlying pathological changes, e.g. how chronic inflammation destroys nerve cells and their connections by using anatomical methods and MRI scans. Finally, we will investigate to what degree curcumin, a natural anti-oxidant and anti-inflammatory compound, can attenuate inflammation, prevent brain damage, and the loss of memory functions in our mice. We expect that our model will assist in the selection of potent candidate drugs, which can then be validated in clinical trials with Alzheimer patients. Aim of Study: The specific aims of this study are: 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the GFAP-IL-6 overexpressing mice during their lifespan. The changes of the brain structure will be also examined by high resolution Magnetic Resonance Imaging (MRI). 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and the interconnected areas using immunohistochemistry. 3. To investigate the effects of a high bioavailable preparation of the anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and cognitive decline. Methods: Specific aim 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the IL-6 overexpressing mice during their lifespan. Research plan: Physical examination of the animals will be carried out before the start of the behavioural testing, to test their sensory abilities (response to auditory, olfactory, somatosensory, taste, vestibular, and visual stimuli), and muscle strength. The performance of transgenic GFAP-IL6 overexpressing mice in special learning tasks (n =12/group, equal distribution of gender) will be compared in several behavioural tests to that of sex- and age-matched wild type controls (littermates) over time. Tests will be taking place at 3, 6, 9, and 12 months of age and different tests will take place on separate days. Both groups (heterozygous and wild type) will go through the same test on one day and testing times will be matched to exclude variance due to diurnal rhythm for each testing session.

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The behavioural tests will include the following: • Open field and elevated O-maze will be used to identify differences between the groups in

exploratory behaviour, anxiety and locomotor activity. The open field test measures hyperactivity, exploratory activity, stereotyped rotation, anxiety and memory for context.

• The novel object recognition test will be used to evaluate cognition, particularly working and recognition memory. This is one particular object recognition task that is sensitive to age-related deficits and is very suitable to test dementia related deficits.

• The T-maze Spontaneous Alternation test will be measuring the willingness of mice to explore new environments. T-maze tasks are characterized and are widely used for cognitive behavioural testing in mice. Many parts of the brain - including the hippocampus, septum, basal forebrain, and prefrontal cortex - are involved in this task.

• The radial arm maze will test the spatial memory of the animals. This maze requires the use of working memory to retain information that is important for a short time (within trial information), as well as the use of reference memory to retain the general rules of the task across days 1.

• The operant conditioning chamber, or Skinner box, will be used to investigate different aspects of learning behaviour (classical and operant conditioning). Animals will be trained to (in most cases) press a lever in response to a specific stimulus (sound, light etc.) in order to receive a reward (often food). In some cases, the missing or giving an incorrect or delayed response is followed by a punishment (air puff, minor electric foot shock).

In-between behavioural testing, mice will be scanned by a high resolution MRI machine (located at UWS, Campbelltown campus), in collaboration with Prof. Bill Price and Dr Tim Stait-Gardner (Nanoscale Group, UWS). Repeated scanning of the same animals will shed light about the progressive changes caused by low-grade neuroinflammation, in particular the effects on the white matter of the brain. Myelination will also be examined in Specific aim 2, by using histochemical techniques. Specific aim 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and its interconnected areas. Research plan: Immunohistochemical investigation of the expression of cholinergic cell bodies and neuritis, calcium-binding protein containing neurons (parvalbumin), IL-6, GFAP, myelination and overall cell numbers will be carried out on both GFAP-IL6 transgenic mice and their wild type littermates. GFAP-IL6 heterozygote transgenic and wild type mice of age from 3 to 12 months (n=7) will be euthanized and transcardinally perfused. Brains will be removed and sectioned at 40 µm with a cryostat the next day in 7 series. Sections will be collected from the entire brain from the olfactory bulb to the cerebellum and analysed by using a research microscope equipped with MBF Biosciences StereoInvestigator to achieve design-based, un-biased quantitative results. On the first series of sections, modified Nissl staining will be performed. Sections of series 2 to 6 will be treated with the following primary antibodies followed by secondary antibodies to visualise cholinergic, parvalbumin, secretagogin, GFAP, IL-6 and IL-6 receptor expressing cells and glia. Myelin silver staining, first described by Gallyas, will be carried out on the last series to visualise myelinated axons. Specific aim 3. To investigate the effects of anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and synaptic decline. Research plan: To test the effects of curcumin on our animal model, a group of GFAP-IL6 heterozygous mice (n=8/group, equal distribution of gender) will be treated with Longvida curcumin in the drinking water (Longvida, Vendure Sciences). Levels of curcumin will be measured from the blood and the brain tissue by using HPLC-MS. Animals will undergo the above-mentioned behavioural tests at the age of 6, 9, 12, 15, and 18 months. Additional 5 groups (n=7) of GFAP-IL6 mice will be also continuously treated, but sacrificed for immunohistological experiments described in Aim 2, to investigate the morphological and gene expression changes during the life span caused by continuous consumption of curcumin. Results will then be compared between the treated, the untreated and wild type groups (using our results from Aim 1 and 2).

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Ethics Application Requirements: Animal Research Authority application has been approved by the UWS Animal Ethics committee to conduct animal research, as documented in Animal Research and Teaching Proposal Number: A10057; Title: Anatomical and behavioural studies of the rodent brain during neuroinflammation in IL6-GFAP mice; at the following site: Animal holdings - C Building 30 SoM animal holdings Key References: 1 Ikegami, S. Behavioral impairment in radial-arm maze learning and acetylcholine content of the

hippocampus and cerebral cortex in aged mice. Behav Brain Res 65, 103-111 (1994). 2 Heyser, C. J., Masliah, E., Samimi, A., Campbell, I. L. & Gold, L. H. Progressive decline in avoidance

learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain. Proc Natl Acad Sci U S A 94, 1500-1505 (1997).

3 Campbell, I. L. et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 2, 125-129 (1997).

4 Campbell, I. L. & Powell, H. C. Role of Cytokines in Demyelinating Disease Studied in Transgenic Mice. Methods 10, 462-477 (1996).

5 Campbell, I. L., Kay, T. W., Oxbrow, L. & Harrison, L. C. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87, 739-742, doi:10.1172/JCI115055 (1991).

6 Campbell, I. L., Eddleston, M., Kemper, P., Oldstone, M. B. & Hobbs, M. V. Activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie. J Virol 68, 2383-2387 (1994).

7 Campbell, I. L. & Chiang, C. S. Cytokine involvement in central nervous system disease. Implications from transgenic mice. Ann N Y Acad Sci 771, 301-312 (1995).

8 Campbell, I. L. et al. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 90, 10061-10065 (1993).

9 Campbell, I. L. Structural and functional impact of the transgenic expression of cytokines in the CNS. Ann N Y Acad Sci 840, 83-96 (1998).

10 Fuller, S., Munch, G. & Steele, M. Activated astrocytes: a therapeutic target in Alzheimer's disease? Expert Rev Neurother 9, 1585-1594, doi:10.1586/ern.09.111 (2009).

11 Maczurek, A., Shanmugam, K. & Munch, G. Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease. Ann N Y Acad Sci 1126, 147-151, doi:10.1196/annals.1433.026 (2008).

12 Steele, M., Stuchbury, G. & Munch, G. The molecular basis of the prevention of Alzheimer's disease through healthy nutrition. Exp Gerontol 42, 28-36, doi:10.1016/j.exger.2006.06.002 (2007).

13 Huber, A., Stuchbury, G., Burkle, A., Burnell, J. & Munch, G. Neuroprotective therapies for Alzheimer's disease. Curr Pharm Des 12, 705-717 (2006).

14 Stuchbury, G. & Munch, G. Alzheimer's associated inflammation, potential drug targets and future therapies. J Neural Transm 112, 429-453, doi:10.1007/s00702-004-0188-x (2005).

15 Munch, G. et al. Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp Brain Res 150, 1-8, doi:10.1007/s00221-003-1389-5 (2003).

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Title of Project: Identification of novel neuroprotective genes Supervisor: Prof. Gerald Muench Email: [email protected] Co-supervisor: Dr. Erika Gyengesi Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Oxidative damage in AD Oxidative damage precedes the appearance of the hallmark pathologies of Alzheimer’s disease. Oxidative stress (imbalance of production and detoxification of reactive oxygen species (ROS)) can be caused by increased production of superoxide (e.g. by mitochondrial dysfunction) and by activation of microglia (e.g. by fibrillar and oligomeric beta-amyloid peptide). Superoxide is then converted to hydrogen peroxide (H2O2), that is usually detoxified by catalase and glutathione peroxidase, but can be converted into the toxic hydroxyl (·OH) radical. Epidemiological studies have also suggested that consumption of foods with high anti-oxidant content might protect against AD However, clinical trials in AD patients with “classical” radical scavengers such as vitamin E and C have shown disappointing results. These data suggest an urgent need for more focused knowledge about relevant therapeutic targets involved in detoxification and/or resistance to ROS. We have generated six different clones of the murine Neuro2A neuronal cell line with an up to 42-fold higher resistance to H2O2 (Table 1), (Maczurek et al., 2013), and analysed the differences in gene expression of all seven cell lines by microarrays. The resistance was not based on increased activity of H2O2 detoxification mechanisms (i.e. catalase or glutathione peroxidase). Aims of Study: We hypothesize that these H2O2 resistant Neuro2A neuronal cells express neuroprotective genes at a higher level (and/or neurotoxic genes at a lower level) than the parent cell line. Aim 1. Identify changes in gene and protein expression between the parental and the six different H2O2

resistant clones Aim 2. Correlate resistance of the clone with the differential expression of specific genes / proteins for the selection of the most promising candidates, based on the continuum of resistance responses Aim 3. Stably overexpress one of the selected genes (one per honours project) in the parental Neuro2A cells and test for an increase in the resistance of these transfected cell lines toward H2O2; and confirming expression changes at the mRNA and protein level. Methods: Plasmid preparation, transfection, cell culture, qPCR, enzymatic assays, cytotocity assays. Ethics Application Requirements: n/a

Key References:

Maczurek AE, Wild R, Laurenti D, Steele ML, Ooi L, Münch G. Generation of hydrogen peroxide-resistant murine neuroblastoma cells: a target discovery platform for novel neuroprotective genes. J Neural Transm. 2013 Aug;120(8):1171-8. doi: 10.1007/s00702-013-0995-z. Epub 2013 Feb 20.

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Title of Project: Tropical rainforest plants as a source of anti-inflammatory compounds for the treatment of Alzheimer’s disease Supervisor: Prof. Gerald Muench Email: [email protected]

Co-supervisor: Frank van der Kooy Email: [email protected]

Co-supervisor: Dr. Erika Gyengesi Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): In Alzheimer’s disease, one of the major causes of neuronal degeneration is chronic inflammation of the brain. Chronic inflammation causes the production of oxygen free radicals (“oxidative stress”), which damage lipids, proteins and DNA, and thus cause cell death. Terrestrial plants have evolved sophisticated antioxidant defenses against oxidative stress including radicals produced by exposure to UV light. One strategy they use is the production of small anti-oxidant compounds such as polyphenols that have been shown to possess antioxidant, anti-inflammatory and neuroprotective properties. Having evolved in tropical latitudes, where exposure to high UV intensities are part of the normal environment, tropical rainforest plants are expected to have also developed efficient defences against the potential damage of long-term solar irradiation and photo-oxidative stress. The identification of such compounds in collaboration with a leading biotechnology company in North Queensland in a variety of high throughput assays will be the major part of this honours project.

Aim of Study: 1) To determine the potency of a variety of extracts from tropical rainforest plants to down-regulate the LPS, IFN-γ -induced production of free radicals (superoxide and nitric oxide) and pro-inflammatory cytokines (IL-6 and TNF) in immortalized murine microglia (anti-inflammatory potential). 2) To fractionate potent extracts and ultimately isolate the active compound, and determine its / their chemical structure (s) using modern analytical and spectrometric methods Methods: Cell culture, ELISA, Natural products extraction, Chromatography, Gas chromatography / Mass spectrometry (GC or HPLC/MS), NMR Ethics Application Requirements: n/a Key References:

Gunawardena D, Shanmugam K, Low M, Bennett L, Govindaraghavan S, Head R, Ooi L, Münch G. Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods. Eur J Nutr. 2013 May 8. [Epub ahead of print]

Steele ML, Truong J, Govindaraghavan S, Ooi L, Sucher NJ, Münch G. Cytoprotective properties of traditional Chinese medicinal herbal extracts in hydrogen peroxide challenged human U373 astroglia cells. Neurochem Int. 2013 Apr;62(5):522-9. doi: 10.1016/j.neuint.2012.08.018. Epub 2012 Sep 11.

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Title of Project: Role of Bacterial Pyocyanin in Modulating Fibroblast Function and Survival Supervisor: Dr Michael Muller Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background: Chronic or non-healing wounds are a common medical problem and a significant cause of disability for many in the community. In recent years, bacterial contamination has been identified as a primary cause for delayed wound healing. Pseudomonas aeruginosa is a common wound pathogen that produces pyocyanin, an extracellular toxin, which we have isolated from infected patients. We have identified pyocyanin as a potent inhibitor of fibroblast replication in vitro and have demonstrated that it significantly delays wound healing in vivo. Fibroblasts play an essential role in wound healing by causing wound tissue to contract. On stimulation in the wound, normal fibroblasts transform into myofibroblasts that exhibit increased expression of extracellular matrix proteins and α-smooth muscle actin (α-SMA). α-SMA enables myofibroblasts to undergo contraction thus contributing to wound closure. When wound healing is complete the myofibroblasts die by apoptosis. Excessive fibroblast transformation, or a failure of apoptosis to occur, can result in tissue fibrosis and hypertrophic scar formation. This project will examine the role of pyocyanin as a modulator of fibroblast transformation, function and survival. Aim of Study: To characterise the responses of human dermal fibroblasts to pyocyanin. Methods: Using tissue culture techniques, the effect of purified pyocyanin on the transformation of human dermal fibroblasts (HDFs) will be assessed by examining the expression of α-SMA and extracellular matrix proteins using immunofluorescence microscopy and biochemical techniques. A collagen-gel wound contraction assay will be used to assess the effects of the toxin on myofibroblasts contraction. HDFs will be incorporated into a three-dimensional collagen gel, stimulated to contract and the extent of gel contraction will be quantified using image analysis techniques. Cell proliferation and survival will be assessed using biochemical and fluorogenic assays. Ethics Application Requirements: None. Key References: Hinz B. Formation and function of the myofibroblast during tissue repair. J. Invest. Dermatol. 127: 526-537, 2007. Muller M, Li Z, Maitz PKM. Pseudomonas pyocyanin inhibits wound repair by inducing premature cellular senescence: role for p38 mitogen-activated protein kinase. Burns 35:500-508, 2009.

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Title of Project: Microvascular Endothelial Cell Responses to Bacterial Pyocyanin Supervisor: Dr Michael Muller Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background: Endothelial cells line the blood vessels forming a barrier between the blood and the tissues. When this barrier is compromised fluid can leak into the surrounding tissue causing swelling and can also allow microorganisms to enter the blood causing bacteremia. The human bacterial pathogen, Pseudomonas aeruginosa, is often associated with burn injuries, chronic wounds and ventilator-associated pneumonia and is a frequent cause of bacteremia, which is often fatal. Vessel colonization and tissue penetration by the bacterium occur predominantly at the post-capillary venules, however, the mechanism by which the Pseudomonas crosses the endothelial barrier to cause bacteremia remains poorly understood. We have shown that pyocyanin, a soluble toxin secreted by the bacterium, is present in the wounds of infected patients and that it redox cycles within host cells generating oxidative stress that profoundly alters cellular behaviour and morphology. This project will examine the role of pyocyanin as a mediator of microvascular endothelial permeability and bacterial transendothelial migration. Aim of Study: To characterise the responses of human microvascular endothelial cells to pyocyanin. Methods: Human dermal microvascular endothelial cells (MVECs) will be grown in culture and treated with concentrations of pyocyanin previously shown to be present in clinical settings. MVECs will be characterized for viability (apoptosis/necrosis), population doubling capacity and tight inter-endothelial barrier function in response to pyocyanin. Pyocyanin-induced oxidative stress will be assessed by determining intracellular hydrogen peroxide production and its influence on cellular glutathione and antioxidant status. These responses will be characterized by standard absorbance, fluorescence and luminescence assays using a multifunction plate reader. To assess compromised barrier function (endothelial leakage) and bacterial transendothelial migration, MVECs will be cultured on transwell membranes that provide access to both sides of the cell surface. MVECs treated with pyocyanin will be examined for endothelial leakage using a fluorescence albumin transfer assay. Bacterial transendothelial migration will be examined using a wild-type pyocyanin producing bacterium and an isogenic mutant unable to produce the toxin. Ethics Application Requirements: None. Key References: Teplitz C: Pathogenesis of Pseudomonas vasculitis and septic lesions. Arch. Path. 80:297-307, 1965. Muller M. Premature cellular senescence induced by pyocyanin, a redox active Pseudomonas aeruginosa toxin. Free Radic. Biol. Med. 41:1670-1677, 2006. Muller M, Li Z, Maitz PKM. Pseudomonas pyocyanin inhibits wound repair by inducing premature cellular senescence: role for p38 mitogen-activated protein kinase. Burns 35:500-508, 2009.

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Title of Project: Efficacy of Silver-Based Wound Materials against Pseudomonas aeruginosa Supervisor: Dr Michael Muller Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background: Silver in its ionic form, but not the bulk metal, is toxic to most microbial life forms and has been used extensively for many years as an effective treatment for wound and burn infections. While bacterial resistance to silver is known to occur it is generally considered rare due to the non-specific nature of silver toxicity. However, the increasing use of silver as an antimicrobial for medical and consumer products has raised concern that widespread silver resistance may emerge. The clinical efficacy of various silver preparations depends on the slow but continual release of low concentrations of silver cation into the wound tissue. Pseudomonas aeruginosa is a common wound pathogen that is difficult to treat due to multiple drug resistance. The bacterium produces an extracellular redox toxin, pyocyanin, which we have discovered confers resistance to ionic silver by converting it to insoluble metallic nanoparticles in the extracellular environment. By this means the bacterium effectively reduces the amount of silver available for bacterial killing. This project will examine the role of pyocyanin as a modulator silver bioavailability and the survival of P. aeruginosa. Aim of Study: To characterise the bioavailability of ionic silver in the presence of a bacterial redox toxin. Methods: The amount of bioavailable (free) silver cation from several commonly used wound dressings and creams will be determined by a spectrophotometric assay. These sources of silver will be tested against two strains of Pseudomonas, a pyocyanin producer and a mutant unable to produce the toxin. Bacterial survival will be determined by the serial dilution plate technique. The bacterial reduction of silver to nanoparticles will be detected by surface plasmon resonance spectroscopy and scanning electron microscopy. Ethics Application Requirements: None. Key References: Muller M, Li Z, Maitz PKM. Pseudomonas pyocyanin inhibits wound repair by inducing premature cellular senescence: role for p38 mitogen-activated protein kinase. Burns 35:500-508, 2009.

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Title of Project: Characterising lipid droplets found in sensory neuropathies Supervisor: Dr Simon Myers Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words) The hereditary neuropathies are the most common group of hereditary disorders presenting to genetic counseling clinics with a prevalence of approx 1 in 2500 population, thus affecting 8000 Australians. Although they are rarely fatal they cause lifelong disability and thus have significant economic impact, estimated to be $180M per annum. No specific treatment is yet available but we have developed a comprehensive management approach to correct the complications of distal weakness and sensory loss that has been widely adopted. Although the causes of hereditary neuropathy are diverse, a common mechanism causes disability, axonal degeneration. The importance of axonal degeneration has is recognized in disorders of the central nervous system eg mutltiple sclerosis and the common neurodegenerations, Alzheimer’s disease and Parkinson’s disease. Axonal degeneration is thought to result from defects in axonal transport (Kamholz et al., 2000), or failure of neurotrophin uptake (Bartlett et al., 1999, Ginty and Segal, 2002) or sodium transport changes. Dominantly inherited neurodegenerations are generally caused by mutations in proteins that lead to cell toxicity (described as a “gain of toxic function”). We found that mutations in the protein, serine palmitoyltransferase (SPT) long chain subunit 1 (SPTLC1) cause a hereditary sensory neuropathy. In hereditary sensory neuropathy (HSN) a mutated enzyme (SPT) becomes toxic and nerves die back from their ends (described as a distal sensory and motor axonopathy). How a mutation in a ubiquitously expressed housekeeping enzyme leads to damage in sensory and motor nerves is completely unexplored. This disorder provides a precise way to determine the pathway that turns a mutant protein into a cell toxin. The link between SPTLC1 mutations and axonal degeneration may prove to be a common mechanism in other neurological disorders and will suggest targets to develop effective therapies. Aim of Study: Overall Aim: is to identify changes in the lipid and lipid droplet profiles due to expression of mutant SPTLC1 in neuronal cells. Our Hypothesis: is that the axonal degeneration in HSN1 is caused by SPTLC1 mutations; which result in the accumulation of lipid droplets in the cell, leading to failed or altered aspects of axonal transport. Specific Aims: (1) To determine by 2-dimensional gel electrophoresis alterations in the lipid droplet profiles caused by the SPTLC1 mutations. (2) To determine using lipidomics, changes to the lipid and sphingolipid profiles due to the SPTLC1 mutations. Methods: Cell culture, 1D and 2DGE, mass spectrometry, protein pull down assays, lipid and shpingolipid microdomain isolations, and flow cytometry. Ethics Application Requirements: None required Key References: Bartlett SE, Reynolds AJ, Hendry IA, (1999) The regulation of the retrograde axonal transport of (125)I-beta nerve growth factor is independent of calcium. Brain Res. 837:8-14 Bejaoui K, Uchida Y, Yasuda S, Ho M, Nishijima M, Brown RH, Jr., Holleran WM, Butt, R.H., Lee, M., Amadi Pershahid, S., Backlund, P., Wood, S., and Coorssen, J.R. (2006) An initial proteomic analysis of human preterm labour: placental membranes. J. Proteome Res. 5, 3161-3172. Hanada K (2002) Hereditary sensory neuropathy type 1 mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis. J. Clin. Invest. 110:1301-1308

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Custer AW, Kazarinova-Noyes K, Sakurai T, Xu X, Simon W, Grumet M, Shrager P (2003) The role of the ankyrin-binding protein NrCAM in node of Ranvier formation. J. Neurosci. 23:10032-10039

Davis BM, Lewin GR, Mendell LM, Jones ME, Albers KM (1993) Altered expression of nerve growth factor in the skin of transgenic mice leads to changes in response to mechanical stimuli. Neurosci 56: 789-792.

Dedov VN, Dedova IV, Merrill AH Jnr, Nicholson GA (2004) Activity of partially inhibited serine palmitoyltransferase is sufficient for normal sphingolipid metabolism and viability of HSN1 patient cells. Biochim. Biophys. Acta. 1688: 168-175

Denny-Brown D (1951) Hereditary sensory radicular neuropathy. J. Neurochem. 14: 237-252

Dyck PJ (1993) Neuronal atrophy and degeneration predominantly affecting peripheral sensory and autonomic neurones. In: Dyck PJ, Thomas, P.K., Griffin, J.W., Low, P.A. & Poduslo, J.F. (ed) Peripheral Neuropathy. W B Saunders, Philadelphia

Fressinaud C, Jean I, Dubas F (2003) Selective decrease in axonal nerve growth factor and insulin-like growth factor 1 immunoreactivity in axonopathies of unknown etiology. Acta Neurpathol. 105: 477-483

Ginty DD, Segal RA (2002) Retrograde neurotrophin signaling: Trk-ing along the axon. Curr Opin. Neurobiology. 12:268-274

Hanada K (2003) Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Bichim. Biophys. Acta. 1632: 16-30

Kamholz J, Menichella D, Garbern JA, Lewis RA, Krajewski KM, Lilien J, Scherer SS, Shy ME (2000)Charcot-Marie-Tooth disease type 1: molecular pathogenesis to gene therapy. Brain. 123: 222-233

Linn SC, Kim HS, Keane EM, Audras LM, Wang E, Merrill AH Jnr (2001) Regulation of de novo sphingolipid biosynthesis and the toxic consequences of its disruption. Biochem Soc Trans. 29:831-835

Mandon EC, Ehses I, Rother J, van Echten G, Sandhoff K (1992) Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase in mouse liver. Journal of Biological Chemistry 267Medlock KA, Merrill AH Jnr (1988) Rapid turnover of sphingoshesized de novo from [14C] serine by chinese hamster ovary cells. Biochem Biophys Res Commun. 157: 232-237

Merrill AH, Jr., Sullards MC, Wang E, Voss KA, Riley RT (2001) Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins. Environmental Health Perspectives. 109:283-9

Molliver DC, Lindsay J, Albers KM, Davis BM (2005) Overexpression of NGF or GDNF alters transcriptional plasticity evoked by inflammation. Pain 113: 277-284.

Rogasevskia T., Coorssen JR (2006) Sphingomyelin-enriched microdomains define the efficiency of native Ca2+-triggered membrane Fusion. J. Cell Sci. 119: 2688-2694

Smith WL, Merrill AH (2002) Sphingolipid metabolism and signaling minireview series. Journal of Biological Chemistry 277:25841-25842

Snell EE, Dimari SJ, Brady RN (1970) Biosynthesis of sphingosine and dihydrosphingsine by cell free systems from Hansenula ciferri. Chem Phys Lipids.5: 116-138

Thomas PK (1993) Hereditary sensory neuropathies. Brain Pathol:157-163

Wagner OI, Ascano J, Tokito M, Leterrier JF, Janmey PA, Holzbaur EL, 2004 The interaction of neurofilaments with the microtubule motor cytoplasmic dynein. Mol. Biol. Cell. 15: 5092-5100

Yasuda S, Nishijima M, Hanada K (2003) Localization, Topology, and Function of the LCB1 Subunit of Serine Palmitoyltransferase in Mammalian Cells. Journal of Biological Chemistry 278:4176-83

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Title of Project: Determining cytoskeletal changes to cellular architecture due to PH domain dynamin 2 mutations Supervisor: Dr Simon Myers Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words) Dynamins are large, 100 kDa mechanochemical GTPases that have a central role in clathrin-mediated endocytosis that interact with functionally diverse SH3 domain-containing proteins (Orth and McNiven, 2003). Dynamin 2 is a member of the dynamin superfamily and is ubiquitously expressed. It has several cellular functions including receptor-mediated endocytosis (RME), a vesicle budding role in the endocytosis of caveolae, phagocytosis, trans-Golgi network budding, cytoskeleton regulation, apoptosis, cell proliferation and cell division (Thompson et al., 2002; Thompson et al., 2004). RME requires Dyn2 GTPase activity to release energy for the process (Hinshaw, 2000). The PH domain binds the lipid PtdIns(4,5)P2, and targets dynamin to the sites of vesicle budding. The GTPase effector domain (GED) is required for the ring assembly process around the neck of invaginating vesicles, whilst the proline rich domain (PRD) regulates activity by phosphorylation (Tan et al., 2003; Larsen et al., 2004). Dyn2 is thought to act at the fission step of clathrin-coated vesicles and is present in the cytosol as dimers or tetramers (Muhlberg et al., 1997). Dynamin’s function during RME is to assemble into ring-like structures around the neck of the budding clathrin-coated pit, where it functions directly or indirectly in severing off vesicles from the plasma membrane (Schmid et al., 1998). Dynamin can act alone or interact with other molecules in vivo to facilitate its function and to assist in its recruitment to clathrin-coated pits (McPherson, 1999; Marsh and McMahon, 1999; Hinshaw, 2000; Hill et al., 2001). Our results showing decreased receptor mediated endocytosis could cause neuropathy through reduced uptake of peripheral trophic factors. However other toxic effects of the mutation such as the changes to cellular architecture and mitochondrial effects are probably more likely in a dominantly inherited disorder. Aim of Study: (1) To identify whether pleckstrin homology domain mutants of dynamin 2 effect the cell cytoskeleton. (2) To determine whether these changes are cell type specific. (3) To ascertain whether the changes observed in the PH domain mutants occur in other domains of dynamin 2. Methods: The methods to be used in this project cover a wide range of molecular and cell biology and biochemical techniques that include: mammalian cell culture, immunostaining, Western Blotting, fluorescence microscopy, electron microscopy and expression vector construction. Ethics Application Requirements: None required Key References: Hill, E., van Der Kaay, J., Downes, C. P., and Smythe, E. (2001), 'The role of dynamin and its binding partners in coated pit invagination and scission', J Cell Biol., 152 (2), 309-23. Hinshaw, J. E. (2000), 'Dynamin and its role in membrane fission', Annu Rev Cell Dev Biol., 16, 483-519. Larsen, M. R., Graham, M. E., Robinson, P. J., and Roepstorff, P. (2004), 'Improved detection of hydrophilic phosphopeptides using graphite powder microcolumns and mass spectrometry: Evidence for in vivo doubly phosphorylated dynamin i and dynamin iii', Mol Cell Proteomics., 3 (5), 456-65. Epub 2004 Feb 2. Marsh, M. and McMahon, H. T. (1999), 'The structural era of endocytosis', Science., 285 (5425), 215-20. McPherson, P. S. (1999), 'Regulatory role of sh3 domain-mediated protein-protein interactions in synaptic vesicle endocytosis', Cell Signal., 11 (4), 229-38. Muhlberg, A. B., Warnock, D. E., and Schmid, S. L. (1997), 'Domain structure and intramolecular regulation of dynamin gtpase', Embo J., 16 (22), 6676-83. Orth, J. D. and McNiven, M. A. (2003), ‘Dynamin at the actin-membrane interface’. Curr Opin Cell Biol., 15,31-39.

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Title of Project: Identifying changes to the neuronal cytoskeleton cause by mutations in the house-keeping protein, SPTLC1 Supervisor: Dr Simon Myers Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words) The sphingolipid pathway is of key importance to neuronal cells; in that they are important second messengers in various cellular events including proliferation, differentiation, senescence, apoptosis and immune response (Linn et al, 2001). Serine palmitoyltransferase (SPT) is a pyridoxal 5’- phosphate dependent enzyme that catalyses the first step of biosynthesis of sphingolipids, including ceramide and sphingomyelin (Snell et al, 1970; Medlock et al, 1988) as well as being important for structural membrane lipids. SPT is a rate-determining enzyme in the sphingolipid synthetic pathway and therefore a key enzyme that regulates cellular sphingolipid content by condensation of palmitoyl coenzyme A (CoA) with L-serine to generate 3-ketodihydrosphingosine (Merrill et al. 2001; Smith and Merrill 2002). There is no evidence that HSN1 neuropathy is caused by loss of function of SPT due to the mutations. We have shown no change in the SPT products between normal versus mutant indicating loss of enzymatic function is not sufficient to cause the disease (Dedov et al., 2004). Bejaoui et al., (2002) showed a 50-70% loss of activity and our laboratory showed 0-30% loss of activity with the same cysteine (133) to tyrosine mutant. The mutation is close to the active site of the enzyme. The newly described glycine (387) to alanine mutation (Verhoeven et al., 2004) may not affect enzyme activity, as it is distant from the active site. We have previously shown that there is some changes to the actin cytoskeleton; this project will explore this finding further. Aim of Study: (1) To determine if mutations in SPTLC1 cause alterations to the actin cytoskeleton. (2) To identify if the intracellular localisation of mutant SPTLC1 is the same as wild type. (3) To determine if microtubule dynamics are altered by mutations in SPTLC1. Methods: The methods to be used in this project cover a wide range of molecular and cell biology and biochemical techniques that include: mammalian cell culture, immunostaining, Western Blotting, fluorescence microscopy, electron microscopy and expression vector construction. Ethics Application Requirements: None required Key References: Hill, E., van Der Kaay, J., Downes, C. P., and Smythe, E. (2001), 'The role of dynamin and its binding partners in coated pit invagination and scission', J Cell Biol., 152 (2), 309-23. Hinshaw, J. E. (2000), 'Dynamin and its role in membrane fission', Annu Rev Cell Dev Biol., 16, 483-519. Larsen, M. R., Graham, M. E., Robinson, P. J., and Roepstorff, P. (2004), 'Improved detection of hydrophilic phosphopeptides using graphite powder microcolumns and mass spectrometry: Evidence for in vivo doubly phosphorylated dynamin i and dynamin iii', Mol Cell Proteomics., 3 (5), 456-65. Epub 2004 Feb 2. Marsh, M. and McMahon, H. T. (1999), 'The structural era of endocytosis', Science., 285 (5425), 215-20. McPherson, P. S. (1999), 'Regulatory role of sh3 domain-mediated protein-protein interactions in synaptic vesicle endocytosis', Cell Signal., 11 (4), 229-38. Muhlberg, A. B., Warnock, D. E., and Schmid, S. L. (1997), 'Domain structure and intramolecular regulation of dynamin gtpase', Embo J., 16 (22), 6676-83. Orth, J. D. and McNiven, M. A. (2003), ‘Dynamin at the actin-membrane interface’. Curr Opin Cell Biol., 15,31-39.

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Title: Use of stem cell-derived lens epithelial cells for anti-cataract drug development. Supervisor: Dr Michael O’Connor Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Surgical treatment of primary and secondary cataracts places a large burden on medical health systems across the globe. The development of anti-cataract drugs that reduce the need for primary or secondary cataract surgery has been severely hampered by limited access to normal human lens tissue. My group previously established a method for generating functional lenses in vitro from rat lens cells; these regenerated rat lenses focus light and ultimately develop a cataract similar to age-related human cataract. More recently, my group established a new method for generating pure populations of human lens epithelial cells from pluripotent stem cells. This new source of human lens cells will enable high-throughput screening for anti-secondary cataract drugs. It may also enable the replacement of existing rat lens cells with human lens cells to regenerate functional human lenses in the laboratory, for use in lens and cataract research as well as toxicology studies of new drugs and cosmetics, and identification of anti-primary cataract drugs. Aim of Study: This study will give students training in key stem cell and regenerative medicine techniques specific to lens and cataract research but also highly relevant to regenerative medicine approaches to all human tissues. Students will be encouraged to present their work at conferences and publish their findings in peer reviewed journals Methods: Students will be taught widely applicable regenerative medicine techniques including tissue culture maintenance of human pluripotent stem cells, directed differentiation to ocular lens cells, and purification of lens epithelial cells. Cell type characterisation will be performed via flow cytometry, polymerase chain reaction, and high-content imaging. This project may involve work with human embryonic stem cells. Ethics Application Requirements: No ethics approval required; biosafety approval already obtained. Key References: 1. O’Connor and McAvoy. In vitro generation of functional lens-like structures with relevance to age-related nuclar cataract. Investigative Ophthalmology and Visual Science. 2007. 48(3):1245-52. 2. Yant et al. Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions. FASEB J. 2010. 24(9):3274-83. 3. Murphy and O’Connor. A rapid, simple and efficient method for generating pure populations of lens epithelial cells from human pluripotent stem cells. In preparation for Stem Cells.

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Title: Characterisation of interstitial cells of Cajal within stem cell-derived intestinal tissue. Supervisor: Dr Michael O’Connor Email: [email protected] Co-supervisor: Dr Vincent Ho Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): The interstitial cells of Cajal (ICC) are the pacemaker cells of the intestine and play a pivotal role in intestinal motility, and are also suspected to be involved in the development of gastrointestinal stromal tumours. Relatively little is known of the molecular development of the ICC due largely to the difficulty in accessing sufficient quantities of human tissue. To overcome this limitation, stem cell-based tissue culture systems have begun to emerge that attempt to produce functional human intestinal tissue in vitro (also known as intestinal organoids). Characterising whether ICC are present within these intestinal organoids will determine to what extent they can be used to model gut development and motility. Aim of Study: This study seeks to give students an appreciation of developmental cell biology and molecular biology while performing a key characterisation of ICC within stem cell-derived intestinal organoids. Students will be encouraged to present their work at conferences and publish their findings in peer reviewed journals. Methods: The student will use a published method, already established at UWS, to generate intestinal organoids from human pluripotent stem cells. This project will involve a brief literature review together with tissue culture, microscopy, molecular biology, and histology techniques (e.g., PCR, immunofluorescence, etc). This project may involve work with human embryonic stem cells. Ethics Application Requirements: No ethics approval required; biosafety approval already obtained. Key References: 1. O’Connor M.D. The 3R principle: advancing clinical application of human pluripotent stem cells. Stem Cell Research and Therapy. 2013. 4(2):21. 2. Spence et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 2011. 470:105-109.

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Title: Production and purification of stem cell-derived endothelial cells to treat vascular disease. Supervisor: Dr Michael O’Connor Email: [email protected] Co-supervisor: Dr Aiden O’Loughlin Email: a.o’[email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): The endothelium is a single layer of cells that separates the blood in the vessel lumen from the components of the vessel wall. Injury to and dysfunction of the endothelium is a central part of the pathophysiology of cardiovascular disease. Stem cell-derived endothelial cells are being used increasingly as therapies for cardiovascular disease. In the area of endovascular prostheses, such as stents, the use of stem-cell derived endothelial cells may provide the benefits of reducing the risk of local thrombosis and restenosis. The development of new treatments for vascular disease has been severely hampered by limited access to normal human endothelial cells for research and transplantation. By using recently published methods to differentiate and purify endothelial cells from human pluripotent stem cells, this project will provide a source of human cells to investigate a new cell transplantation approach to treating vascular disease being developed within the UWS School of Medicine. Aim of Study: This study will give students training in key stem cell and regenerative medicine techniques specific to endothelial cell production for vascular disease treatment, but also highly relevant to regenerative medicine approaches to all human tissues. Students will be encouraged to present their work at conferences and publish their findings in peer reviewed journals Methods: Students will be taught widely applicable regenerative medicine techniques including tissue culture maintenance of human pluripotent stem cells, directed differentiation to endothelial cells, and purification of endothelial cells. Purified cells will be cultured on various surfaces in preparation for transplantation into an animal model of vascular disease. Characterisation of the purified endothelial cells will be performed via flow cytometry, polymerase chain reaction, and immunofluorescence. This project may involve work with human embryonic stem cells. Ethics Application Requirements: No ethics approval is required for the laboratory component; animal ethics approval for cell transplantation is in process. Biosafety approval already obtained. Key References: 1. Haude et al. The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent. JACC Cardiovasc Interv. 2013. 6(4):334-43. 2.Dichek et al. Seeding of intravascular stents with genetically engineered endothelial cells. Circulation 1989. 80(5):1347-1353. 3. Van Der Giessen et al. Endothelialization of Intravascular stents. Journal of Interventional Cardiology. 1988. 1(2): 109-120. 3.Tatsumi et al. Simple and highly efficient method for production of endothelial cells from human embryonic stem cells. Cell Transplant. 2011. 20(9):1423-30.

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Title of Project: Competing epistemologies, CAM and interdiscinplinarity in 21st century health care Supervisor: Dr Rebecca Olson Email: [email protected] Co-supervisor: Dr Sue Cochrane Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Wasserman and Hinote (2011, p. 55) write that ‘perspectives resting at a singular level of scale explain less and less of our world.’ We typically prescribe to multiple and dialogic definitions of reality and philosophies of knowledge, ranging from religious to constructivist to positivist (Capra, 1982; Holland, 1998; Little, 1995). Health care is increasingly interdisciplinary, with multiple practices allowing for more holistic care. Biomedical research, based on a positivist epistemology, maintain a dominant position within Australia. In 2012 a lobby group called ‘Friends of Science in Medicine’ urged universities to stop offering degrees in complementary and alternative medicine (CAM) (Schwager, 2012). This very public epistemological struggle illustrates the difficulties often faced in coming to terms with our pluralistic ways of knowing, being and acting. Interested honours students should become familiar with philosophy of knowledge debates and philosophers, especially Jullien and Barad. Jullien (2009) identifies Chinese thinking as being deliberately indeterminate, explaining that standard methods of biomedical science fail to fully comprehend the vitality of qi and the relational dynamism of yin-yang because the biomedical way of knowing favours almost exclusively observation through sight. Barad (2003; 2007; 2008) points to the importance of diffractive methods, focusing on relationality rather than objects. Aim of Study: This honours project explores the ways patients, practitioners, students and the public manage competing epistemologies in health. The project is appropriate for health science student from any discipline (TCM, PT, Pod, etc.) interested in the philosophy of knowledge. Methods: Possible research methods might include: 1) critical discourse analysis of publications and social media discussions on CAM and epistemology in health care practices (no ethical approval required); 2) interviews (n=10-20) with students, lecturers and patients on epistemology and practice (ethics required); 3) other methods negotiated between the student and supervisors. Ethics Application Requirements: Approval from the UWS Human Research Ethics Committee (HREC) may be required depending on the method selected (see above). Key References: Barad, K. (2003). Posthumanist performativity: Toward an understanding of how matter comes to matter. Signs: Journal of Women in Culture and Society, 28 (3), 801-831. Barad, K. (2007). Meeting the universe halfway: Quantum physics and the entanglement of matter and meaning. Durham, NC: Duke University Press. Barad, K. (2008). Living in a posthumanist material world: Lessons from Schrodinger’s cat. In A. Smelik and N. Lykke (Eds.) Bits of life: Feminism at the intersections of media, bioscience and technology. Seattle: University of Washington Press. Capra, F. (1982). The turning point: Science, society, and the rising culture. London: Flamingo. Csordas, T. (2006). Preface. In H. Johannessen and I. Lazar (Eds.) Multiple medical realities: Patients and healers in biomedical, alternative and traditional medicine (pp. ix-xi). New York: Berghahn Books. Holland, D., Lachicotte, W., Skinner, D., & Cain, C. (1998). Identity and Agency in Cultural Worlds. Cambridge, MA: Harvard University Press. Johannessen, H. (2006). Introduction. In H. Johannessen and I. Lazar (Eds.) Multiple medical realities: Patients and healers in biomedical, alternative and traditional medicine (pp. 1-15). New York: Berghahn Books. Jullien, F. (2009). The great image has no form: On the nonobject through painting. Chicago: The University of Chicago Press. Little, M. (1995). Humane medicine. Cambridge: Cambridge University Press. Sauer, U. (2007). Getting closer to the whole picture. Science, 316, 550.

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Schwager, S. (2012, February 21). War against natural medicine. The Drum Opinion on ABC news 24. Retrieved from http://www.abc.net.au/unleashed/3840682.html Wasserman, J. A., & Hinote, B. P. (2011). Chronic illness as incalculable risk: Scientific uncertainty and social transformations in medicine. Social Theory & Health, 9, 41–58. doi:10.1057/sth.2010.4

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Title of Project: Hydration status and thermoregulation in Indoor Hockey Goalies. Supervisor: Dr Shona Papalia Email: [email protected] Co-supervisor: tba Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): Indoor hockey is a variation of the team sport field hockey played indoors. In Australia the competitive season is during the hot summer months. Indoor hockey is a highly skilled fast paced game requiring goalkeepers to wear full body protective equipment. Heat related stress in goalies may be increased by the wearing of such equipment through impairment of thermoregulatory function (1). No research to date has been conducted on the hydration status and thermoregulation of indoor hockey goalies. Aim of Study: 1. To determine the thermoregulatory responses of goalkeepers during indoor hockey games played in hot, humid environments. 2. Investigate the relationship between hydration status and thermoregulatory responses. Methods:

• Recruit indoor hockey goalkeepers • Assessment of thermoregulatory responses to heat exposure during indoor hockey games

through the use of core temperature chips and analysis of hydration status Ethics Application Requirements: Ethics clearance has already been obtained. Key References: American College of Sports Medicine. Position Stand: Exertional heat illness during training and competition. Med Sci Sports Exerc. 2007;19:529–533. doi: 10.1249/MSS.0b013e31802fa199 Hargreaves M. Physiological limits to exercise performance in the heat. J Sci Med Sport. 2008;11(1);6. doi: 10.1016/j.jsam.2007.07.002]

Armstrong LE, Johnson EC, Casa DJ, Ganio MS, McDermott BP, Yamamoto LM, Lopez MR, Emmanuel H. The American football uniform: Uncompensable heat stress and hyperthermic exhaustion. J Ath Train. 2010;45(2);117-127. doi: 10.4085/1062-6050-45.2.117 Malan M, Dawson B, Goodman C, Peeling P. Effect of heat exposure on thermoregulation and hockey-specific response time in field hockey goalkeepers. J Sci Med Sport. 2010;13;371-375. doi: 10.1016/j.jsams.2009.03.009 Brothers RM, Mitchell JB, Smith ML. Wearing a football helmet exacerbates thermal load during exercise in hyperthermic conditions. Med Sci Sports Exerc. 2004;36;S48. Available from: http://journals.lww.com/ Godek SF, Bartolozzi AR, Godek JJ. Sweat rate and fluid turnover in American football players compared with runners in a hot and humid environment. Br J Sports Med. 2005;39(4);205-211. doi: 10.1136/bjsm.2004.011767

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Title of Project: The interaction between mitochondrial function and sphingolipid metabolism. Implications for programmed cell death and human diseases. Supervisor: Dr Gabriel Perrone Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Sphingolipids play key roles in a broad range of cellular processes including: the formation of lipid micro domains “rafts” in membrane bilayers, that influence protein sorting and signal transduction; signaling molecules in cell differentiation, growth and cell cycle progress/arrest, cholesterol metabolism and stress signaling; and immune function, endocytosis and programmed cell death. Due to the role of sphingolipids in important cellular processes the impact of altered sphingolipid metabolism can have very serious consequences for cells. Altered sphingolipid metabolism has also been shown to play an important role in the pathobiology of diseases including: cancer, diabetes and metabolic syndrome; heart disease; Alzheimer’s disease; Niemann-Pick; and immune dysfunction. In some cancers altered sphingolipid homestasis appears to play a key role in disease progression. Crucially, despite the role of sphingolipids in a diverse range of serious human diseases, on a global or a “systems-wide” level very little is known of how the broad array of cellular functions influence sphingolipid homeostasis and/or vice-versa. Recently we have identified novel links between mitochondrial function and sphingolipid metabolism. This is a two bidirectional effect whereby altered mitochondrial function impacts on sphingolipid metabolism, and conversely, we have identified cases were altered sphingolipid metabolism disrupts mitochondrial respiration. Aim of Study: To investigate how mitochondrial dysfunction (e.g. respiratory ) leads to abnormal sphingolipid homeostasis, and, vice-versa how defects in sphingolipid metabolism impact mitochondrial function, including respiratory capacity. This study also aims to identify on a genome-wide level how the various process conducted in cells affects sphingolipid metabolism. The findings will help us to better understand the factors that contribute to abnormal sphingolipid metabolism and inform our understanding of diseases (e.g. metabolic syndrome, cancer, neurodegenerative diseases) where altered sphingolipid metabolism has been implicated. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) as well as leading edge techniques and resources. The project will exploit the genome-wide deletion strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, lipid analyses, as well as suite of powerful yeast strain libraries that allow us to selectively manipulate almost all genes (deletion or overexpression) in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to readily test most hypotheses. This project will utilise sophisticated analytical methodology including flow cytometry, mass spectrometry and fluorescent microscopy If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: none required Key References: A range of relevant references can be provided upon request

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Title of Project: Investigating the link between DNA synthesis/repair, redox balance and production of free radicals Supervisor: Dr Gabriel Perrone Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of certain free radical species. Cells are equipped with key systems (e.g. glutathione) that maintain redox balance. Altered redox balance is associated with many diseases including, cancer, diabetes, neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases, and has been implicated as an important factor regulating cell growth and ageing. Cells of are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease, arthritis and those listed above. Altered lipid metabolism has also been associated with many of the above diseases. Maintenance and repair of DNA and maintenance of an optimal redox environment are closely linked through their requirement for NADPH as a cofactor. NADPH is used in the synthesis of DNA but is also used to keep redox/protective systems in balance. Combined treatments of cells with agents that affect redox systems in conjunction with DNA damaging agents has shown strong efficacy in treatment of some cancers. Surprisingly there an indepth understanding of how changes in DNA metabolism affect the ability of cells to maintain their redox environment and vice-versa is lacking. Aim of Study: This project will study how the DNA synthesis and repair mechanisms of cells is impacted by changes in redox balance. The project also aims to study the converse, that is how changes in DNA homeostasis affect a cells ability to maintain redox balance and detoxification of reactive oxygen species. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: none required Key References: A range of relevant references can be provided upon request

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Title of Project: Investigating the role of yeast suicide proteins mitochondrial function and programmed cell death, and implications for antifungal drug therapy Supervisor: Dr Gabriel Perrone Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Humans are exposed to potentially pathogenic fungi on a daily basis. In most cases fungal infections tend to be superficial (non-life threatening) however for a growing number individuals including those that are immune compromised, transplant patients, those undergoing cancer chemotherapy, newborns and the old, fungal infections can pose a serious threat to their survival. Superficial fungal infections can also have a major impact on well being and can cause prolonged suffering. While antifungal drug treatments are available, in cases of invasive life threatening fungal infections, morbidity can be as high as 40% even when individuals are treated with frontline drugs, including amphotericin B. While amphotericin B is the gold standard for antifungal therapy treatment with the drug is associated with toxicity. Analysis of genome-wide screening data has identified a that proteins known as the yeast suicide proteins, and a related group of additional proteins play a crucial role in protecting fungi against a range of antifungal agents including amphotericin B. While mutants disrupted in these suicide proteins are hypersensitive to certain antifungal drugs, the function of these proteins in normal cell function or in response to antifungal drug treatment is limited. The proteins of interested have been shown to play a role in fungal programmed cell death and mitochondrial function. More specific details of the identity of the genes/proteins that we are interested in studying will be discussed in private with potentially interested students. Aim of Study: This project will utilise the model eukaryotic/fungal organism Saccharomyces cerevisiae to investigate the function of the suicide proteins, their precise role in daya to day functions, and in programmed cell death. Furthermore the project seeks to determine the how such proteins protect fungi against specific antifungal agents. A better understanding of the function of these suicide proteins may not only identify novel ways to improve antifungal drug therapy but the data may also have implications for understanding programmed cell death and mitochondrial function in humans. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) as well as cutting edge techniques and resources. The project will also exploit the genome-wide deletion strain collections, drug treatments, chemical-genetic screening, a range of recombinant DNA and protein analysis techniques, biochemical assays, lipid analyses, as well as suite of powerful yeast strain libraries that allow us to selectively manipulate almost all genes (deletion or overexpression) in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to readily test most hypotheses. This project will also exploit use of sophisticated analytical methodology including flow cytometry, mass spectrometry and fluorescent microscopy. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: none required Key References: A range of relevant references can be provided upon request

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Title of Project: Investigating the link between lipid metabolism, redox balance and production of free radicals Supervisor: Dr Gabriel Perrone Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of certain free radical species. Cells are equipped with key systems (e.g. glutathione) that maintain redox balance. Altered redox balance is associated with many diseases including, diabetes, neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases, and has been implicated as an important factor regulating cell growth and ageing. Cells of are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease, arthritis and those listed above. Altered lipid metabolism has also been associated with many of the above diseases. Lipid metabolism and maintenance of an optimal redox environment are closely linked through their requirement for NADPH as a cofactor. NADPH is used in the synthesis of many lipid species (e.g. sterols, phospholipids and sphingolipids) but is also used to keep redox/protective systems in balance. Surprisingly there an indepth understanding of how changes in lipid metabolism affect the ability of cells to maintain their redox environment and vice-versa is lacking. Aim of Study: This project will study how changes in the metabolism of lipids (e.g. sterol synthesis) and impacts on redox balance and the ability of cells to detoxify free radicals. The project also aims to study the converse, i.e. whether changes in redox balance impact on lipid homeostasis. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy, chromatography and mass spectrometry. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, lipid analyses, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: none required Key References: A range of relevant references can be provided upon request

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Title of Project: Protein arginine methylation – a key player in cellular events Supervisor: Sabine C. Piller Email: [email protected] Co-supervisor: TBA depending on project Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): Protein arginine methylation is a post-translational modification like phosphorylation, acetylation and ubiquitination. Recent research and advances in technology have revived the initial research carried out on protein methylation in the early 1960ies (1), and protein arginine methylation has become one of the hot topics of research in a variety of fields including virology, cell biology and molecular mechanisms of disease as well as potential drug target development. Protein arginine methyaltion is a likely key modulator of cellular processes such as transcription, cell signalling, nuclear transport, ageing and cellular stress which has implications for a wide range of diseases including cancer, cardiovascular diseases, viral infection, lung disease and potentially neuronal diseases. Protein arginine methyltransferases (PRMTs) are a protein family that is highly conserved and can even be found in yeast (2). There are now 4 types of PRMTs known and arginine residues can be mono-methylated on the terminal nitrogen (by types, I, II and III) or on an internal nitrogen (by type IV). Arginine residues can further be modified by type I PRMTs resulting in asymmetric dimethylation of the terminal nitrogen, while type II PRMTs result in symmetric dimethylation of the terminal nitrogens. This field of research is fast moving and new findings about the mechanism and importance of protein arginine methylation are discovered and published every month. My lab has started to study protein arginine methylation initially in the HIV virus (3, 4) and work continues to clarify the role of protein arginine methylation of 2 HIV proteins. In addition, we have obtained preliminary data suggesting that arginine methylation may be important in the ageing process and may overlap with traditional Chinese herbal medicines used as anti-ageing compounds. Further, the work of one of my PhD students in 2011 has identified neuronal proteins that are methylated. We are in the process of studying the importance and role of protein arginine methylation in neurons and neuronal diseases as well as in other diseases including hepatitis and liver diseases. Other areas of interest include studying the role of protein arginine methylation in cyanobacteria, bacteria and other microorganisms (collaborative projects with Dr Michelle Moffitt, Dr Oliver Morton, and Dr Colin Stack), in plants and mycorrhizal fungi (in collaboration with Dr Jonathan Plett at the HIE) and in ion channel forming proteins. Honours projects are available for each of the above mentioned aspects of the overall focus to elucidate the molecular mechanism of protein arginine methylation. Aim of Study: The major aim of the work conducted in my laboratory is to better understand protein arginine methylation and its importance in cellular pathways and disease in order to identify potential future drug targets to combat a variety of diseases. The specific aims and individual projects include: 1. Role of protein methylation in neurons and neuronal disease 2. Role of protein methylation in liver disease 3. Role of protein methylation in the regulation of cell cycle and cancer (in collaboration with Dr Simon

Mahoney) 4. Role of protein methylation in viral diseases including HIV, HCV, HBV 5. Role of protein methylation in mycorrhizal fungi (in collaboration with Dr Jonathan Plett) 6. Role of protein methylation in microorganisms including cyanobacteria (co-supervised project with

supervisor Dr Michelle Moffitt) 7. Role of protein methylation in ion channel forming proteins 8. Role of protein methylation in ageing 9. Role of protein methylation in nuclear transport Methods: The major methods and techniques employed include, cell and tissue culture techniques (bacteria, yeast, eukaryotic cells), transformation, transfection, plasmid DNA preparations and

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purifications, PCR, site-directed mutagenesis, SDS-PAGE, agarose gels, Western Blotting, immunoprecipitation, FACS studies, fluorescent confocal microscopy, and potentially some advanced microscopy techniques (FRET) ; 2D gels and mass spectrometry. Reagents and infrastructure as well as expertise with techniques is available in the Piller laboratory and from national and international collaborators (including Prof Muench at SoM, Ass/Prof Roslyn London at UWA, Dr Michelle Moffitt, Dr Colin Stack, Dr Oliver Morton, Dr Patrice Castignolles, Dr Simon Mahoney; SSH; Dr Jonathan Plett; HIE). Ethics Application Requirements: Most experiments are performed in cell lines and ethics approval for mouse work is to be submitted in September 2013. Key References: Paik et al. 2007 Trends in Biochemical Sciences 32(2):146-152; Bedford and Clarke 2009 Molecular Cell 33: 1-13; Willemsen et al. 2006 Retrovirology 3:92; Mirto & Piller 2010 Future Medicine - HIV Therapy 4(1): 65.

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Title of Project: Investigation of diffusive averaging and viscosity effects in bimodal polymer solutions Supervisor: Prof. William S. Price Email: [email protected]

Co-supervisor: Dr Gang Zheng Assoc. Prof. Gary Dennis Dr Scott Willis

Email: [email protected]/ [email protected] [email protected]

Campus project is offered and conducted: Campbelltown Background (200 words): The most fundamental form of molecular transport is self-diffusion – the random motion of molecules – and measurements of which provide information on the size of the molecule as well as any influences from restrictions/obstructions (e.g., diffusion in a cell or porous rock) or aggregation processes (e.g., drug-binding). A powerful, versatile and non-invasive method for measuring self-diffusion is pulse gradient spin-echo (PGSE) nuclear magnetic resonance (NMR). However, measurements of self-diffusion in polydisperse systems (e.g., polymer solutions with different molecular weight polymers present or aggregating proteins) is complicated by diffusive averaging effects since the NMR signals are the same or overlapped. Studying diffusive averaging in bimodal polymer solutions is of great significance as synthetic (e.g., polystyrene) and natural (e.g., proteins) polymers are inherently polydisperse. In this project, diffusive averaging will be studied for different bimodal polymer solutions (i.e., two molecular weights or two types of polymers present) of either chemically identical polymers of different molecular weights or mixtures of chemically different polymers of different or similar molecular weights. Several types of polymers could be considered for this study. Measurements of the viscosity of bimodal and monomodal polymer solutions will help to elucidate the diffusive averaging processes. (Would suit students interested in Physical chemistry/Mathematics/NMR) Aim of the Study: To use NMR diffusion measurements and viscosity measurements to develop better models for diffusive averaging phenomena. Methods: Viscometry and NMR diffusometry. Ethics Application Requirements: Not applicable. Key References: Price, W. S., NMR Studies of Translational Motion. Cambridge University Press: New York, 2009. Willis, S. A.; Dennis, G. R.; Zheng, G.; Price, W. S. Macromolecules 2010, 43, 7351-7356. Willis, S. A.; Price, W. S.; Eriksson-Scott, I. K.; Zheng, G.; Dennis, G. R. J. Mol. Liq. 2012, 167, 110-114. Callaghan, P. T.; Pinder, D. N. Macromolecules 1985, 18, 373-379.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

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Title of Project: Investigating Restricted Diffusion using NMR Techniques Supervisor: Prof. William S. Price Email: [email protected]

Co-supervisor: Dr Bahman Ghadirian Email: [email protected] Campus project is offered and conducted: Campbelltown Background (200 words): Modelling self-diffusion in complicated geometries is of fundamental importance in many areas of science including medicine. Modelling diffusion-controlled reactions - which occur widely in chemical and biochemical systems, and nuclear magnetic resonance diffusion experiments in bounded systems provide many prominent examples of where such modelling is required. Using a simple cellular system as an example, a reacting species diffuses to the enzymatic membrane and then reacts in some way, being either transformed into a product, becoming bound to the surface or transported through the surface. The nature of the interaction at the surface determines the boundary conditions in the modelling. Presently only solutions for some simple geometries are available. This is a serious impediment as most real-world structures that chemical reactions occur in have complicated geometries. Thus, there is a need to develop techniques for modelling diffusive processes near surfaces which are applicable to different geometries and arbitrary boundary conditions. (Would suit students interested in Biology/Chemistry/Mathematics/Medical Physics/MRI/NMR) Aim of the Study: To develop theoretical and experimental method for investigating diffusion in restricted systems and studying their application. Methods: Analytical modelling and numerical computer programming in Mathcad or Matlab, and testing the models using NMR experiments. Ethics Application Requirements: Not applicable. Key References: C. H. Neuman, J. Chem. Phys. 60, 4508 (1974). S. D. Traytak and W. S. Price, J. Chem. Phys. 127, 184508 (2007). G. A. Truskey, F. Yuan, and D. F. Katz, Transport Phenomena in Biological Systems. (Pearson, London, 2004). W. S. Price, NMR Studies of Translational Motion. (Cambridge University Press, Cambridge, 2009). D. G. Duffy, Mixed Boundary Value Problems. (Chapman & Hall / CRC, New York, 2008). B. Ghadirian, A. M. Torres, N. N. Yadav, and W. S. Price. J. Chem. Phys. 138:094202-1-094202-11 (2013).

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

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Title of Project: Studying Ice Nucleation Protein Motifs with NMR Diffusion Measurements Supervisor: Prof. William S. Price Email: [email protected] Co-supervisors: Dr Scott A. Willis, Dr Allan Torres, Dr Gang Zheng Campus project is offered and conducted: Campbelltown Background (200 words): Freeze tolerance is important for life that exists in low temperature environments. Protection strategies include the use of antifreeze proteins to prevent ice crystal growth or the use of ice nucleation proteins (INPs).1, 2 INPs initiate ice formation earlier so that the organism has a chance to respond to the freezing for thermal protection or could be used as a means of retrieving nutrients from plants.1 INPs are thought to bind to water molecules in a way that resembles an ice crystal3 such that further nucleation is promoted but the mechanism is not fully understood. As such a study of translational diffusion4 and hydration of these proteins in aqueous solutions at various temperatures is pertinent for understanding this and would be of interest for potential applications of these proteins. (Would suit students interested in Biology/Chemistry/NMR) Aim of the Study: This project aims to investigate particular motifs common in INPs via NMR diffusion methods at various temperatures to determine if they are useful for ice nucleation. Methods: NMR Diffusion Experiments + Analysis Ethics Application Requirements: N/A. Key References:

1. Zachariassen, K. E., Kristiansen, E., Cryobiology, 2000, 41, 257 – 279. 2. Graether, S. P., Jia, Z., Biophysical Journal, 2001, 80, 1169 – 1173. 3. Green, R. L., Warren, G. L., Nature, 1985, 317, 645 – 648. 4. Price, W. S., NMR Studies of Translational Motion. Cambridge University Press: New York, 2009.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

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Title of Project: Investigating Biostructures using NMR/MRI Supervisor: Prof. William S. Price Email: [email protected]

Co-supervisor Dr Tim Stait-Gardner Email: [email protected] Campus project is offered and conducted: Campbelltown Background (200 words): Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise tissue microstructure on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of the Study: To characterise a variety of tissue microstructures (mainly brain and muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: May be necessary for some tissue samples. Key References: W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

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Title of Project: MRI-based Electron Density Mapping for Radiotherapy Treatment Planning Supervisor: Prof. William S. Price Email: [email protected] Co-supervisors: other members of the Nanoscale Group + Dr Stephen Bosi (UNE) Campus project is offered and conducted: Campbelltown Background (200 words): Radiation therapy is a recommended treatment for approximately half of cancer cases [Delaney et al 2005]. Accurate planning of radiation dose requires both a picture of a patient's tissues and a map of the "electron density" of these tissues, currently obtained using CT (or "CAT") scans which use ionising radiation. At present an electron density (ED) map derived from a CT of the patient is the minimum requirement for treatment planning (TP) for external beam radiotherapy. Magnetic resonance imaging (MRI) scans actually provide a clearer tissue image than CT scans (and without using ionising radiation), but traditional medical MRI methods cannot provide a density map – at least not at the present time. Development of a new method which allows MRI to be used to measure tissue composition AND density would eliminate the extra radiation dose of a CT scan and streamline treatment planning. (Would suit students interested in Biology/Chemistry/Medical Physics/NMR) Aim of the Study: The aim is to develop a method allowing MRI scanners to provide a tissue density map which is required for accurate radiation dose planning for radiation therapy. Methods: MRI Experiments + Analysis Ethics Application Requirements: N/A as only phantoms will be used in this project. Key References:

5. Delaney G., Jacob S., Featherstone C. et al. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 104 1129-1137 (2005).

6. Khan F.M. "The Physics of Radiation Therapy" - 3rd ed., Lippincott & Wilkins. Philadelphia USA, 2003.

7. Wu Y., Reese T.G., Cao H., et al. Bone Mineral Imaged In Vivo by 31P Solid State MRI of Human Wrists J. Magn. Reson. Imaging. 34, 623–633 (2011).

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

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Title of Project: NMR Simulation using Symbolic Algebra

Supervisor: Prof. William S. Price Email: [email protected]

Co-supervisor Dr Tim Stait-Gardner Email: [email protected]

Campus project is offered and conducted: Campbelltown Background (200 words): Understanding spin-dynamics is of fundamental importance for NMR students. However, in many instances to understand such complicated theory we must resort to computer simulation, which turns boring memorization into exciting practice. Numerical and symbolic algebra simulation programs can be used for the development of new NMR pulse sequences. In this project students will perform NMR simulations based on a full understanding of spin-dynamics to enhance the development of new NMR methods (e.g. water suppression and diffusion measurements). Exact numerical simulations of NMR experiments are often required for the development of new techniques and for the extraction of structural and dynamic information from the spectra. (Would suit students interested in Mathematics/MRI/NMR/Physics) Aim of the Study: In this project, user friendly liquid state NMR simulation software will be developed based on density matrix, product operator and quaternion theories by the use of symbolic algebra software (e.g. Mathematica, Maple). The newly developed software will be distributed around UWS to assist NMR teaching and scientific research. Methods: Nuclear Magnetic Resonance Spectroscopy and computer simulation. Ethics Application Requirements: N/A Key References: W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. R.P.F. Kanters et al., A Computer-Algebra Application for the Description of NMR Experiments Using the Product-Operator Formalism, J. Magn. Reson. 101, 23-29, 1993.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

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Title of Project: Expanding the Boundaries and Applications of Diffusion NMR

Supervisor: Prof. William S. Price Email: [email protected]

Co-supervisor Dr Allan Torres Email: [email protected]

Campus project is offered and conducted: Campbelltown Background (200 words): Diffusion NMR is routinely used to study various molecular properties, and interactions occurring in solution. This technique is also valuable in MRI as it can be used to probe microscopic structures in biological tissues. Recently, long-lived singlet spin states have been used in NMR diffusion and diffusion-diffraction studies. Unlike regular spin coherences, singlet spin states have significantly longer lifetimes on the order of tens of seconds to a minute making it feasible to study extremely slowly diffusing molecules. In diffusion-diffraction studies, long lived singlet states can potentially be useful for probing structures with larger characteristic distances. In this project, the restricted diffusion of test molecules in glass and flexible silica capillaries will be investigated by utilising singlet spin states and various NMR coherences. The feasibility of performing NMR diffusion experiments in a single capillary with internal diameter of 10-200 micrometers will also be studied. (Would suit students interested in NMR/Physical Chemistry/Physics) Aim of the Study: To characterise NMR diffusion in capillaries using various spin coherences and singlet spin states. Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not applicable Key References: M. Carravetta and M.H. Levitt, Long-lived nuclear spin states in high-field solution NMR. J. Am. Chem. Soc. 126 (2004) 6228-6229. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. N.N. Yadav, A.M. Torres and W.S. Price, NMR q-space imaging of macroscopic pores using singlet spin states. J. Magn. Reson. 204 (2010) 346-348. A.M. Torres, B. Ghadirian and W.S. Price, Diffusion-diffraction using singlet spin states and various NMR coherences in a J-coupled AX spin system. RSC Advances 8 (2012) 3352-3360.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

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Title of Project: Brain-boosting to enhance learning Supervisor: Dr Siobhan Schabrun Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Imagine a future where learning to move can be enhanced. The implications are far-reaching, from reduced rehabilitation times and quicker recovery after injury or illness, to improved training regimes for athletes and new strategies for maintaining function in old age. This future may soon be a reality. Non-invasive brain stimulation (NIBS) has enormous potential to revolutionise the way we learn. Indeed, preliminary studies from our group and others, suggest NIBS is effective at boosting learning. However, it is unclear when NIBS should be applied relative to training or therapy (i.e. should NIBS be applied before, during or after training/therapy) to give the greatest boost to learning. This study will be the first to investigate this important question. This work will have widespread implications for the design of NIBS therapies to boost learning in healthy individuals, athletes and individuals with neurological conditions such as stroke. We anticipate that this study will result in conference presentations and a journal publication for the involved honours student. Aim of Study: To determine whether non-invasive brain stimulation applied i) before, ii) during or iii) after training on a complex movement task has the greatest effect on learning. Methods: Healthy individuals will be recruited for this study. We will make measures of learning using a complex visuomotor transformation task and brain mechanisms using transcranial magnetic stimulation before and after non-invasive brain stimulation applied i) before, ii) during or iii) after a period of movement training. The three conditions will be assessed in three different experimental sessions. Ethics Application Requirements: Ethical approval has already been obtained. Key References: Schabrun, S. & Chipchase, L. Priming the brain to learn: the future of therapy? Man Therap 17(2012). Schabrun. Priming the brain to learn: the future of therapy? Man Therap, 2012.

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Title of Project: Boosting the effects of exercise with non-invasive brain stimulation in knee osteoarthritis Supervisor: Dr Siobhan Schabrun Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Osteoarthritis (OA) is a major public health problem and a leading cause of disability in Australia. Exercise is considered the corner-stone of conservative management and is recommended in all clinical guidelines internationally. Although exercise is effective in knee OA, meta-analyses indicate the treatment benefits are moderate at best. Innovative treatments that bolster the effects of exercise have the potential to improve outcomes in knee OA. Non-invasive brain stimulation (NIBS) is a powerful new technique with the potential to boost the brain’s receptiveness to other treatments. By increasing brain activity under electrodes positioned on the scalp, NIBS can facilitate brain plasticity and improve the brain’s response to traditional therapies such as exercise. This raises the exciting possibility that NIBS may improve clinical outcomes beyond that which can be achieved with exercise alone in knee OA. This innovative study will be the first to test this possibility. We anticipate that this study will result in conference presentations and a journal publication for the involved honours student. Aim of Study: To determine the effect of a non-invasive brain stimulation and exercise treatment on pain/disability and pain system function in knee OA. Methods: This study is a small randomised, controlled clinical trial with two treatment groups i) exercise therapy alone and ii) combined brain stimulation and exercise therapy. Each group will have 10 subjects with knee OA (20 subjects in total). We will make measures of pain, disability and pain mechanisms before and after 8 weeks of treatment (2 x per week). Ethics Application Requirements: An amendment to an existing approved ethical protocol is required. Key References: Schabrun, S. & Chipchase, L. Priming the brain to learn: the future of therapy? Man Therap 17(2012). Schabrun. Priming the brain to learn: the future of therapy? Man Therap, 2012.

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Title of Project: Treating chronic headache from the top-down and the bottom-up Supervisor: Dr Siobhan Schabrun Email: [email protected] Co-supervisor: Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): Chronic tension-type headache (CTTH) is a major health problem with few effective therapies. This novel study will test the feasibility, safety and clinical benefit of two interventions (brain and spinal cord stimulation) with the potential to reduce headache severity and ease the burden of care associated with this prevalent condition. Whereas spinal direct current stimulation targets pain mechanisms from the periphery and spinal cord (bottom-up), direct current applied to the brain exerts its effects through the modulation of brain plasticity (top-down). Targeting multiple pain mechanisms simultaneously is a promising and innovative approach that may improve clinical outcomes in CTTH. This study will be the first to examine the effect of a combined brain and spinal cord direct current stimulation intervention in a persistent pain population. This approach will not only provide preliminary examination of the clinical benefits of brain and spinal cord stimulation, but will also provide the first examination of the pain mechanisms that are modified when these techniques are combined. We anticipate that this exciting new project will result in conference presentations and a journal publication for the involved honours student. Aim of Study: To investigate the effect of a novel direct current stimulation therapy, applied to the brain and spinal cord, on the severity, frequency and duration of chronic headache. Methods: This study is a small randomised, controlled clinical trial with three treatment groups i) brain stimulation alone, ii) spinal cord stimulation alone and iii) dual brain and spinal cord stimulation. Each group will have 10 subjects (30 subjects in total). We will make measures of clinical outcomes such as headache severity, frequency and duration to determine whether this new therapy is effective. We will also make measures of pain mechanisms, such as central sensitisation, to determine which physiological changes underpin any improvement in clinical outcomes. Ethics Application Requirements: An amendment to an existing approved ethical protocol is required. Key References: Schabrun, S. & Chipchase, L. Priming the brain to learn: the future of therapy? Man Therap 17(2012). Lyngberg, A.C., Rasmussen, B.K., Jorgensen, T. & Jensen, R. Has the prevalence of migraine and tension-type headache changed over a 12-year period? A Danish population survey. Eur J Epidemiol 20, 243-9 (2005).

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Title of Project: Muscle oxygenation and Intermittent Hypoxic Training: Role of acid-base balance Supervisor: Jason Siegler Email: [email protected] Co-supervisor: Kenneth Graham Email: [email protected] Campus/s project is offered and conducted: Primary campus is Campbelltown, however data collection will take place at the New South Wales Institute of Sport (NSWIS) Background (200 words): The efficacy of introducing ‘altitude’ as a means of enhancing a training stimulus or adaptation, whether through hypobaric exposure, altering the fractional content of inspired oxygen (FiO2) or actual sojourns to altitude, has been widely researched since the late 1960’s. Although much of the research initially focused on acclimation and/or acclimatization strategies and endurance performance, there has been a recent trend to explore the efficacy of intermittent hypoxic exposure (IHE) on short-duration, high intensity exercise performance. However, there is potential for hypoxia to inhibit training intensity and therefore diminish the overall training stimulus. One potential biochemical contributor to the decline in training intensity observed during IHT is the marked increase in intramuscular acidity. A prospective intervention for reducing this decline in pH and power output during IHT may be through the acute administration of a metabolic buffer or alkaline agent prior to exercise. To our knowledge, there have been no human studies examining the effects of alkalosis during IHT conditions. Aim of Study: The aim of this study will be to investigate the effects of acute NaHCO3 supplementation and hypoxia on repeated bouts of high-intensity cycling performance. Methods: More than one student may work on this project, as there will be various measurements of muscle function, muscle oxygenation and exercise performance included in this project. The general design will require the student(s) to become experienced in working with various methods of metabolic analysis (e.g. blood sampling) and muscle function (e.g. neuromuscular assessment techniques, functional capacity, muscle oxygenation using near-infrared spectroscopy (NIRS)), as well as performance testing on a cycle ergometer under hypoxic conditions. Ethics Application Requirements: The core project has ethical approval (H9383), however a minor amendment will be required depending on number of students involved, and for the use of the NIRS technique. Key References: 1. Brosnan MJ, Martin DT, Hahn AG, Gore CJ, Hawley JA. Impaired interval exercise responses in elite female cyclists at moderate simulated altitude. J Appl Physiol. 2000;89:1819–1824. 2. Roels B, Bentley DJ, Coste O, Mercier J, Millet GP. Effects of intermittent hypoxic training on cycling performance in well-trained athletes. Eur J Appl Physiol. 2007;101(3):359–368. 3. Eiken O, Tesch P. Effects of hyperoxia and hypoxia on dynamic and sustained static performance of the human quadriceps muscle. Acta Physiol Scand. 1984;122:629–633.

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Title of Project: The role of acupuncture with managing cardio-vascular outcomes in women Supervisor: A/Prof Caroline Smith Email: [email protected] Co-supervisor: Dr Suzanne Cochrane Email: s.cochrane.edu.au Co-supervisor: Dr Xiaoshu Zhu Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words):

Cardiovascular disease (CVD) is one of the leading causes of death and disability in women worldwide. Sex and gender differences exist which interact to increase the risk of CVD for women. The prevalence of CVD is significantly higher in women at 55% compared with 45% in men (1). Data from the Women's Ischemia Syndrome Evaluation (WISE) study (2) suggests adverse coronary reactivity, micro-vascular coronary dysfunction, and plaque erosion or distal micro-embolisation maybe in part responsible for the female specific myocardial ischemia pathophysiology.

There is increasing literature on the role acupuncture may be used to treat a variety of chronic health conditions including cardiovascular dysfunction. A variety of mechanistic research has been published proposing potential mechanisms underlying cardiac ischemia, hypertension and hypotension through stimulation of acupuncture points activate sensory neural pathways that stimulate regions in the central nervous system (3). There is increasing evidence that acupuncture is used by patients to assist with the management of cardio-vascular disease (4). The knowledge base of acupuncture’s cardiovascular actions has significantly increased over the decades, however, the influence of gender specific data on cardiovascular disease within acupuncture studies is unclear. Aim of Study:

1) To explore the effects of sex specific research on cardiovascular disease in the acupuncture literature

2) To examine women’s interest to participate in a clinical study of acupuncture.

Methods: The study will involve:

1) Review of the literature relating to acupuncture and its cardio-vascular properties undertaking sex specific review. The literature will be systematically searched to identify key articles. This data will be extracted and the literature synthesised.

2) Women with a history of CVD will be recruited from the community to participate in a study to explore their experience of managing heart disease, and to their views about engaging in a trial of acupuncture. A survey of a self completion questionnaire will be designed. Follow up interviews will be undertaken with a small sample of women to explore areas of the survey in greater detail.

The student will obtain experience with different methodologies, and the study has the potential to lead onto a higher degree.

Ethics Application Requirements: Ethics approval will be sought. Key References: 1. Australian Institute of Health and Welfare Women's Health 2008. Canberra2008 Contract No.: Cat No AUS 99. 2. Ciambrone G, Kaski JC. The importance of geneder differences in the diagnosis and management of cardivascular disease. Curr Pharm Des. 2011;17:1079-81. 3. Longhurst JC. Acupuncture’s Cardiovascular Actions: A Mechanistic Perspective. Medical Acupuncture. 2013;25(2):101-13. 4. Grant SJ, Bin YS, Kiat H, Chang DH-T. The use of complementary and alternative medicine by people with cardiovascular disease: a systematic review. BMC Public Health. 2012 Apr 26;12:299. doi: 10.1186/1471-2458-12-299.

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Title of Project: The patient-practitioner relationship Supervisor: Caroline Smith Email: [email protected] Co-supervisor: Sarah Fogarty Email: [email protected] Campus/s project is offered and conducted: Campbelltown

Background (200 words):

Acupuncture is a complex intervention involving a patient –practitioner relationship. The development of the therapeutic relationship is an integral part of acupuncture in clinical practice (1). The acupuncture consultation involves close interaction between the patient and therapist and as reported by Paterson et al (2012) the consultation involves active participation by both patient and practitioner (2). There is increasing interest in acupuncture by women using IVF and a University of Western Sydney study is investigating the effectiveness of acupuncture in improving the proportion of live birth rates for women undergoing in vitro fertilisation (IVF). This randomised controlled trial compares acupuncture to a control group for women undergoing IVF. The study is currently recruiting women from 12 IVF Centre in Australia and New Zealand (3). As part of this study we are collecting data from participants about their views towards their participation in the study, and their experience of receiving the study intervention. The Honours study presents an opportunity to explore this data, and to engage with acupuncturists to seek their views on the therapeutic relationship they form with their patients. This study will be of interest to a student studying traditional Chinese medicine but also from other health sciences disciplines. Aim of Study: To examine aspects of the acupuncture consultation and treatment process. The study will examine questions including:

1. What are the most important features of the consultation and treatment session with the acupuncturist?

2. Why are these important? 3. How do these features relate to questionnaires used to assess the therapeutic alliance. 4. What are acupuncturists’ views about the therapeutic relationship?

Methods: A literature view will be undertaken examining the characteristics of the practitioner –client relationship and examined in the context of Models of Health and Models on Interaction from other health disciplines. Questionnaires with open and closed questions relating to the consultation and treatment, and a questionnaire relating to the communication within the consultation have been completed by women on finishing their participation in a clinical trial. This data is to be analysed. Additional data collection can be collected from the therapists involved in the study to obtain their views on the therapeutic relationship. Ethics Application Requirements: An amendment to an existing ethics application to conduct interviews with practitioners will be submitted.

Key References: 1. Bishop FL, Lewith GT. A Review of Psychological Predictors of Treatment Outcomes:

What Factors Might Determine the Clinical Success of Acupuncture for Pain? Journal of Acupuncture and Meridian Studies 2008;1(1):1-12.

2. Paterson C, Evans M, Bertschinger R, Chapman R, Norton R, Robinson J. Communication about self-care in traditional acupuncture consultations: The co-construction of individualised support and advice. Patient Education and Counseling 2012.

3. Smith CA, de Lacey S, Chapman C, Ratcliffe, Norman R, Johnson N, Sacks G, Lyttleton J, Boothroyd C. Acupuncture to improve live birth rates for women undergoing in vitro fertilisation a protocol for a randomised controlled trial. Trials 2012, 13:60.

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Title of Project: How to dismantle a parasite. Supervisor: Colin Stack Email: [email protected] Co-supervisor: Oliver Morton Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Trichomonads are protists that are primarily studied because of their medical and veterinary importance. The most important members are Tritrichomonas foetus and Trichomonas vaginalis, both of which are parasites of the urogenital tract of cattle and humans, respectively. Currently there is no vaccine available. An effective vaccine would be invaluable and important for the future control or prevention of these diseases. However, before this can be done more basic biological information is required to provide understanding of the immunological interaction(s) [both protective and pathological] between the host and the parasite. Cysteine proteases (CPs) are important drug targets for several pathogen species and make up a large proportion of protozoan transcriptomes. Because T. foetus is an obligate extracellular pathogen, adherence to epithelial cells is critical for survival and establishment of infection within the host. CPs released by T. foetus are capable of directly inducing apoptosis of cultured bovine reproductive tract cells and as such represent key virulence factors against therapeutic could be designed. Aim of Study: The aim of the study is to understand the mechanism/interaction at the key battleground the host-parasite interface. The approach we will use in our study will be to incubate separately living parasites and their excretory/secretory products (i.e. CPs) to a cultured epithelial cell line and study the ability of the parasite or extracts (CPs) to induce host cell apoptosis. We will then develop a methodology to inhibit the abilities of the parasite and CPs to induce apoptosis. Methods: This study will involve parasite cell culture, culturing of epithelial cells, basic cysteine protease assays, cell transfection, gene cloning and PCR, recombinant protein expression and protein gel electrophoresis, and apoptosis assays. Ethics Application Requirements: No ethics applications required Key References:

Lucas JJ, Hayes GR, Kalsi HK, Gilbert RO, Choe Y, Craik CS, Singh BN. (2008) Characterization of a cysteine protease from Tritrichomonas foetus that induces host-cell apoptosis. Arch Biochem Biophys.; 477(2):239-43.

Mallinson DJ, Livingstone J, Appleton KM, Lees SJ, Coombs GH, North MJ. (1995) Multiple cysteine proteinases of the pathogenic protozoan Tritrichomonas foetus: identification of seven diverse and differentially expressed genes. Microbiology; 141 ( Pt 12):3077-85.

Sommer U, Costello CE, Hayes GR, Beach DH, Gilbert RO, Lucas JJ, Singh BN. (2005) Identifcation of trcihomonas vaginalis cysteine proteases that induce apoptosis in human vaginal epithelial cells. J Biol Chem.; 280(25):23853-60.

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Title of Project: Baroreflex control of muscle sympathetic nerve activity: effect of time of day? Supervisor: Dr. Chloe Taylor Email: [email protected] Co-supervisor: Prof. Vaughan Macefield Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): It is well known that blood pressure exhibits a circadian rhythm, with the highest pressures occurring in the morning following nocturnal sleep. Research also suggests that blood pressure responses to physical activity are greater at this time of day (Jones et al., 2006). This may be explained by diurnal variation in the body’s ability to buffer changes in blood pressure. Recent evidence indicates that important mechanisms of blood pressure regulation, such as the cardiovagal baroreflex, are less sensitive in the morning compared with the afternoon (Taylor et al., 2011). The cardiovagal arm of the baroreflex regulates blood pressure mostly through the modulation of heart rate. However, it is not known whether diurnal variation exists in the sympathetic arm of the baroreflex, which regulates blood pressure via changes in muscle sympathetic nerve activity (causes constriction of blood vessels). This information will help to unravel the mechanisms behind the morning surge in blood pressure. Aim of Study: To determine whether sympathetic baroreflex sensitivity differs between the morning and the afternoon in healthy young individuals. Methods: Microneurography is an invasive technique that involves the insertion of a fine needle electrode into a nerve. In this study the electrode will be inserted into a muscle fascicle of the peroneal nerve (in the leg, at the level of the fibular head) in order to continuously record spontaneous bursts of muscle sympathetic nerve activity. Blood pressure, heart rate, respiration, and sweat release will be measured continuously and non-invasively. Baroreflex function will be assessed using spontaneous methods at rest, and also during a series of manoeuvres. These will include breathing manoeuvres (inspiratory apnoea and end-expiratory apnoea), the Valsalva manoeuvre, the cold pressor test (cold-water hand immersion) and post-exercise ischaemia (occlusion of blood flow following handgrip exercise). Each subject will perform the experiment twice (once in the morning and once in the afternoon). Ethics Application Requirements: Ethical approval has been granted (H9577) Key References: Jones H, Atkinson G, Leary A, George K, Murphy M, Waterhouse J. (2006). Reactivity of ambulatory blood pressure to physical activity varies with time of day. Hypertension 47: 778-84. Taylor CE, Atkinson G, Willie CK, Jones H, Ainslie PN, and Tzeng YC. (2011). Diurnal variation in the mechanical and neural components of the baroreflex. Hypertension 58: 51-56.

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Title of Project: The meaning of participation in craft/hobby activities amongst baby boomers living in Western Sydney: a qualitative study. Supervisor: Dr Leigh Wilson Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): A large number of post WWII baby boomers, born between 1946 and 1965 have reached retirement age1. Baby boomers are more educated, have travelled more frequently and are more health conscious than the previous generation2. They are also more likely to be influenced by marketing and media, and have a higher rate of divorce and independent living status2. As the baby boomer generation reaches older age, many have opted to make significant lifestyle changes and take up volunteer roles in the community to ‘give back’ after working for the majority of their adult lives3. Research suggests that upon, or as they reach retirement baby boomers (particularly women) pursue craft activities and hobbies they have previously had little time to undertake4. It is therefore reasonable to assume that many retired or semi-retired baby boomers participate in craft activity groups. Research has shown that participation in craft activities in a group setting reduces social isolation and has a positive effect on mental health in older women5, but no research has been conducted on the meaning of participation in craft activities in the (younger) baby boomer generation specifically. Aim of Study: Using qualitative methods, this study aims to:

• Explore the meaning of participation in craft / hobby activity groups in those who are part of the baby boomer generation.

• Identify the reasons for participation in group craft/hobby activities and • Explore the opinions of group participants on the effects of craft/hobbies on health

Methods: Study type: This study uses a phenomenological approach to explore the meaning of participation in craft and hobby activities in a group of baby boomers in western Sydney. Sampling and target population: Using purposive sampling and conducting focus groups and individual face to face interviews, the researchers will collect qualitative data from individuals living in the western Sydney region of Sydney, NSW, who were born between 1946 and 1965 (inclusive) and who participate in group craft/hobby groups. Recruitment: Established craft/hobby groups across western Sydney will be identified using internet searching and liaison with local Councils and Community Centres. Letters of invitation explaining the project and outlining the enrolment criteria will be sent to groups identified. Project flyers will be sent to interested groups with the option for groups or individuals to participate in the study. It is anticipated 6 focus groups and 10 individual interviews will provide an information-rich pool of data, however should new themes still continue to emerge recruitment will continue until data saturation is reached.

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Interviews and focus groups: Individual face to face interviews and focus groups will be conducted with those who wish to enrol in the study. Fully informed consent will be required prior to any interview or focus group participation. All participants will be provided with a Study Information Sheet prior to signing an informed consent document. Interviews will take up to one hour, and will be made at a time to suit the participant(s). A semi-structured interview schedule will be used to guide the interview /focus group. All participants will be asked if they consent to audio-recording of the interview or focus group. Where there are objections to this the interview/focus group will not be recorded. Notes and reflective jottings will also be taken as part of data collection. Analysis: Data will be entered into NVivo software for analysis. Key themes and concepts will be identified in all data and narrative analysis will be conducted on individual interviews. Interrogation of the data will enable the development of general theories from phenomenological findings. Ethics Application Requirements: Ethics application in progress Key References: 1. Australian Bureau of Statistics (2009). Retirement Intentions of Australian Baby Boomers. Accessed

online 12th August 2013. www.abs.gov.au/ausstats/abs

2. Productivity Commission (2011). Caring for Older Australians: Productivity Commission Inquiry Report. Volume 1, Number 53: 28th June 2011. ISBN 978-1-74037-360-9 (Volume 1)

3. Ozanne E. (2009) Negotiating identity in later life: Diversity amongst the Australian Baby Boomers.

Australian Social Work : 62(2): p.132-154. 4. Byles J, Tavener M, Robinson I. et al. (2013) Transforming retirement: new definitions of life after

work. Journal of Women & Aging, 25:24–44. 5. Liddell J. (2013) A mixed methods study exploring how participation in art and craft activities relates

to health in women aged in their eighties. PhD Thesis, School of Medicine, University of Newcastle.

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Title of Project: Sudden and Unexpected Death in Western Sydney Infants: a survey of risk reduction factor knowledge in multicultural western Sydney: “5 years on” Supervisor: Dr Leigh Wilson Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Western Sydney is one of the most multicultural regions of New South Wales with around 30% of the population born overseas. Around one third of the Western Sydney population has migrated to Australia and half of the world’s nations are represented among its residents. In the Fairfield LGA alone, over 70 different languages are spoken while Auburn is home to people from over 100 nations1. ‘The largest urban communities of Aboriginal and Torres Strait Islander people live in the region, primarily in the Blacktown, Campbelltown, Liverpool and Penrith LGAs. Western Sydney is where young people are choosing to begin their families. The population is younger on average than for Sydney generally. More than 1 in 3 people (37.3%) in Western Sydney are aged 24 years and under’2.

Sudden unexpected Death in Infancy is still one of the leading causes of infant death in Australia. Although health promotion campaigns have significantly reduced the numbers of SUDI, research conducted in 2008 highlights the higher than average rate of SUDI in multicultural and Indigenous families3. Following the research conducted by Wilson in 2008 the NSW Ministry of Health changed policy guidelines to include ‘cultural group of parents’ on all SUDI documentation. This has enabled a review of the cultural groups whose infants may be at particular risk of SUDI. The 2011 Child Death Review Team Report indicates that 19% (9/48) of SUDI deaths were in families from a multicultural background4.

There has been an increased focus on SUDI risk reduction education in multicultural groups, however the high number of infant deaths in this population suggests that knowledge barriers may still exist in these communities4. Aim of Study: The aim of this study is to investigate the SUDI risk reduction factor knowledge in multicultural communities in western Sydney and compare this to the levels of knowledge in a similar study conducted 5 years ago. Methods: Study design: This is a cross-sectional survey of SUDI risk reduction factor knowledge in the Western Sydney multicultural community. Sampling and target population: Participants will be recruited using convenience sampling across the Greater Western Sydney Region. The target population will be anyone aged over 18 years of age who lives in the region. Recruitment: Recruitment will take place in collaboration with multicultural community groups and local councils across the region. Participants will be invited to participate in the study with a flyer printed in multiple languages. Participants wishing to participate in the study will be provided with informed consent documents in their preferred language. Recruitment will continue until at least 100 participants have been enrolled into the study.

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Survey: Participants will be asked to complete a short 10 question survey in their preferred language. This survey replicates the survey used in the 2008 study by Wilson et al. This survey will be hard copy, however participants also have the option of completing the survey online (using survey monkey). Analysis: Once recruitment is complete data will be entered into SPSS and analysis will commence. Data will be analysed to investigate the characteristics of SUDI risk reduction knowledge by age, sex, cultural group and parental status. Data will then be compared to data collected in a similar study 5 years ago (2008) to determine whether there are any differences in levels of knowledge. It is anticipated this study will further inform the development of health promotion material and SUDI risk reduction education messages across the western Sydney Region. Ethics Application Requirements: Ethics application in progress Key References: 1. Australian Bureau of Statistics (2011) Census data.

2. NSW Government Department of Premier and Cabinet: Western Sydney Demographics. Accessed

13th August 2013: Available at: http://www.westernsydney.nsw.gov.au/about-western-sydney/demographics/

3. Wilson LA, Quine S, Lewis M. (2008). Sudden Infant Death in Infants and Parental Infant Care: A study n multicultural western Sydney. Published Thesis: University of Sydney. Available at: http://ses.library.usyd.edu.au/bitstream/2123/6275/1/L-Wilson-2008-Thesis.pdf

4. Child Death Review Team (2011). Report of the Review Team into Child Deaths in NSW. NSW

Ombudsmans Office. ISBN 978-1-921884-77-1 http://www.ombo.nsw.gov.au/__data/assets/pdf_file/0015/7053/CDRT-Annual-Report-2011.pdf

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Title of Project: Tornadoes and health: The Australian experience. Supervisor: Dr Leigh Wilson Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): As a result of climate change and global warming, extreme weather events are becoming more intense, more frequent and more severe1. Tornadoes have been documented in Australia as far back as 1834, however an increase in population density and numbers suggest that there are more tornadoes reported now than previously. Because tornadoes are considered rare in Australia, compared to the United States of America, they are often referred to as ‘mini-tornadoes’ or ‘mini-cyclones’. Irrespective of the terminology, tornadoes in Australia cause catastrophic damage to infrastructure and devastating loss to those affected2. The unpredictable and sudden nature of tornadoes in Australia reduces the ability of communities to prepare for such events3. Research conducted overseas highlights the importance of rehabilitation following a tornado event but there is limited literature on the long term levels of stress, depression and anxiety in people who have experienced a tornado event. Research on the psychological effects of tornadoes in those who have experienced a tornado in the Australian context has never been undertaken, although research into other extreme weather events such as heatwaves and floods in Australia clearly indicates an increase in stress and anxiety after such events4,5. Aim of Study: The aim of this study is to explore the effect of tornadoes on self reported levels of depression, stress and anxiety in those who have experienced a tornado event in Australia and assess whether these are different to population norms. Methods: Study design: This is a mixed methods study conducted in two phases.

• The first phase of the study uses quantitative methods to collect information on levels of depression, anxiety and stress in people who have experienced a tornado event.

• The second phase of the study uses qualitative interviews with a sub-group of those enrolled in

Phase 1 of the study. Sampling and target population: The target population for this study are adults aged over 18 years who have experienced a tornado event in Australia. The researchers will advertise for participants through Universities, Local Councils, community organisations, emergency service organisations and local media. It is anticipated 200 people will need to complete the online survey using the Depression, Anxiety Stress Score Scale (DASS) in order to gain sufficient data to detect a 5% change in stress and anxiety levels (from population normal data) at alpha 0.5 with a power of 80%. Ten participants will be selected to participate in a telephone interview of 20 minutes duration following the initial survey to collect qualitative narrative data.

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Recruitment: Participants will be recruited in towns/regions known to have experienced a ‘mini-tornado’ event. Such regions include: the Illawarra (2013), Riverina (2013), Northern NSW (2012). Recruitment will be through advertisement in local newspapers, flyers in local community centres and through local councils. Participants will be asked to complete the online survey if they are interested in participating in the study. A full description of the study and consent to participate will be embedded in the online survey. Within the online survey there will be a question asking whether the participant would be prepared to participate in a telephone interview of 20 minutes duration. Participants who reply ‘yes’ to this question, will be grouped separately and 10 will be randomly selected to participate in the interview. Interviews and focus groups: Interviews with 10 randomly selected participants will be conducted by telephone. The interview will be scheduled at a time to suit the participant and will be guided by a qualitative interview schedule which is designed to capture the narrative experience of the participant at the time of the tornado. Analysis: Demographic data will be presented as descriptive data to clearly define the sample population who participated in the study. Data from the online survey will be entered into SPSS and scores for each of the depression, anxiety and stress scales will be calculated for participants. Age, sex and length of time since the tornado experience will be controlled for using logistic regression analysis. Data will be compared to Australian population norm scores for the DASS scales. Qualitative data collected through telephone interview will be analysed using narrative analysis. Ethics Application Requirements: Ethics application in progress Key References: 1. Steffan W. (2009) Climate Change (2009). Faster Change & More Serious Risks. Report of the

Australian Department of Climate Change. Commonwealth of Australia 2009 ISBN: 978-1-921298-58-5. 2. Australian Bureau of Meteorology (2013). Tornadoes in NSW – Factsheet. Accessed 13th August 2013.

Available at: http://www.bom.gov.au/nsw/sevwx/tornadofact.shtml 3. McAneney, T (2010) Adaptation lessons from cyclone Tracey. National Climate Change Adaptation and

Research Facility (NCCARF): Published Factsheet.

4. National Climate Change Research Facility (2013) Community Adaptation Strategies to Floods in Australia. Published Factsheet. Accessed 13th August 2013. Available at: http://www.nccarf.edu.au/sites/default/files/attached_files_publications/Flooding-CommunityAdaptationStrategies-factsheet.pdf

5. Wilson LA, Veitch C, Black DA (2012) HeatSafe: A preliminary study investigating heat-wave perception in a group of Australians aged 75+. International Journal of Aging in Society, 1(3): 25-32.

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Title of Project: Cloning and characterisation of putative aluminium transporter in Saccharomyces cerevisiae Supervisor: Dr Ming Wu Email: [email protected] Co-supervisor: Dr Zhonghua Chen Email: [email protected] Campus/s project is offered and conducted: Campbelltown and Hawkesbury Background (200 words): Metal ion homeostasis is fundamental to cell function. The tight control of metal ion uptake in the cell is elaborately regulated via gene expression and signal transduction. The key frontline molecule in this process is the transporters in plasma membrane. In the past studies, we have tried to understand aluminium toxicity using the model organism, Saccharomyces cerevisiae. The complete set of deletion mutants (5047) was screened using a range of concentrations of aluminium sulfate (0.4 mM, 0.8 mM, 1.6 mM and 3.2 mM). Two standing-out genes are found to be involved in Al transport. Their deletion leads to the Al resistance phenotype. This project is to clone the two genes and further investigate their role in Al transportation. Aim of Study: To clone the putative Al transporters and further investigate their role in Al transportation Methods: Cytotoxicity assays, Molecular cloing and expression, confocal microscope, ICP-MS and PCR Ethics Application Requirements: No required Key References: Can be requested by email.

125

Title of Project: Neurons under the metal overload Supervisor: Dr Ming Wu Email: [email protected] Co-supervisor: Dr Cindy Kersaitis Email: [email protected] Co-supervisor: Prof. Gerald Muench Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Metal ions, lifeless on their own, can affect cellular metabolism in beneficial or harmful ways. This project focuses on aluminium (Al3+), iron (Fe2+/3+), copper (Cu2+) and zinc (Zn2+). Al3+ is becoming a health threat because of its increased presence in our drinking water, food and other beverages due to prevalent soil acidity, climate change and pollution. Years of chronic aluminium accumulation in humans may pose a health problem in the later stages of life. For example, an eight-year longitudinal study on a large French population supports the hypothesis that a high concentration of aluminum in drinking water may be a risk factor for Alzheimer’s disease. Interestingly, the danger of aluminium usage in food was warned 100 years ago by William Gies. We found that a concentration of 400 µM aluminium sulfate is mildly toxic to yeast cell growth whilst 3.2 mM of the aluminium salt is lethal. Various organic phosphate compounds, such as phospholipid, phosphorylated proteins and nucleic acids, are the strong binders of Al3+. Substantial evidences indicate that there is a role for Al3+ in amyloid β (Aβ) aggregation. Chronic Al3+ feeding rat model produced AD-like symptoms and neuropathology. Residues such as histidine in Aβ are able to coordinate Al3+. In consideration of these together, this project will investigate the cytotoxicity of Al3+ in neurons, together with the transitional metal ions Fe2+/3+, Cu2+ and Zn2+. Aim of Study: To understand the uptake and toxicity of the metal ions in neurons Methods: Neuron cell line culture, Cytotoxicity assays, confocal microscope, ICP-MS and qPCR Ethics Application Requirements: No required Key References: Can be requested by email.

126

Title of Project: Decode Nature’s Way of Detoxification – NMR Studies on Dissolved Organic Matter in Australian Aquatic Systems

Supervisor: Dr Gang Zheng Email: [email protected]

Co-supervisor Prof. William S. Price Email: [email protected]

Campus project is offered and conducted: Campbelltown Background (200 words): Like ourselves, mother nature has many methods for detoxification. Dissolved organic matter (DOM) plays a major role in natural detoxification in aquatic systems. In fresh water, many harmful versions of heavy metals (e.g., methyl-mercury) latch onto DOM then are more likely broken down into harmless compounds by sunlight. In sea water, however, these nasty metal complexes tend to latch onto salt (i.e., sodium chloride) instead of DOM and therefore are far more likely accumulated through the food chain, according to studies by a US researcher. In this study, the key chemical components of the various DOM in Australian aquatic systems will be identified, their roles in the natural detoxification will be revealed, and environmental factors (e.g., salt) affecting the detoxification process will be identified. (Would suit students interested in Biology/Chemistry/NMR/Physics) Aim of the Study: To unveil the role of each key chemical component of DOM in natural aquatic detoxification. Methods: Nuclear Magnetic Resonance Spectroscopy, Fluorescence Spectroscopy, Size Exclusion Chromatography Ethics Application Requirements: Not Applicable. Key References:

1. G. Zheng and W.S. Price, Direct hydrodynamic radius measurement on dissolved organic matter in natural waters using diffusion NMR. Environ. Sci. Tech., 2012. 46(3): p. 1675-1680.

2. G. Zheng, T. Stait-Gardner, P.G. Anil Kumar, A.M. Torres, and W.S. Price, PGSTE-WATERGATE: An STE-based PGSE NMR sequence with excellent solvent suppression. J. Magn. Reson., 2008. 191: 159-163.

3. G. Zheng and W.S. Price, Solvent signal suppression in NMR. Prog. Nucl. Magn. Reson. Spec., 2010. 56: 267-288.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

127

Title of Project: Quantitative Composition-Flavour Relationships: the first step to a flavour tasting machine Supervisor: Dr Gang Zheng Email: [email protected]

Co-supervisor Prof. William S. Price Email: [email protected] Campus project is offered and conducted: Campbelltown Background (200 words): Have you ever thought about why different wines have different tastes? What is controlling the flavour? What chemicals contribute to the flavour generation process? Are these chemicals staying as monomers or forming assemblies in the wine? The results of this study will answer all these tricky questions. (Would suit students interested in Biology/Chemistry/NMR/Physics/Statistics/Wine tasting) Aim of the Study: To build an NMR-based wine tasting machine Methods: Nuclear Magnetic Resonance Spectroscopy Pattern Recognition Ethics Application Requirements: Not Applicable. Key References:

1. Hu, N., D. Wu, K. Cross, S. Burikov, T. Dolenko, S. Patsaeva, and D.W. Schaefer, Structurability: A collective measure of the structural differences in vodkas. Journal of Agricultural and Food Chemistry, 2010. 58(12): p. 7394-7401.

2. Polášková, P., J. Herszage, and S.E. Ebeler, Wine flavor: Chemistry in a glass. Chemical Society Reviews, 2008. 37(11): p. 2478-2489.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

128

Title of Project: Advanced Water Signal Suppression in in vivo NMR Spectroscopy Supervisor: Dr Gang Zheng Email: [email protected]

Co-supervisor Prof. William S. Price Email: [email protected] Campus project is offered and conducted: Campbelltown Background (200 words): In mammalian tissue, the common metabolites (e.g., tCr and NAA) used in NMR based disease diagnosis are present in concentrations several orders of magnitude smaller than water. Consequently, in vivo proton NMR spectra are overwhelmed by the extremely strong water signal, thereby preventing accurate detection of metabolites and thus the diagnostic value is unreliable. In this study, advanced water signal suppression techniques will be developed for better detection of metabolites and thus more accurate NMR based disease diagnoses. (Would suit students interested in Biology/Chemistry/Medical Physics/MRI/NMR) Aim of the Study: To build advanced water signal suppression techniques for in vivo NMR spectroscopy Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: N/A Key References:

S.W. Provencher, Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 1993. 30(6): p. 672-679. G. Zheng and W. S. Price. Solvent Signal Suppression in NMR. Prog.NMR Spectrosc. 56 (3): 267-288, 2010.

This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis).

129

Title of Project: Chinese herbal medicine for local treatment-related side effect in women with breast cancer: development of a clinical protocol Supervisor: Dr Xiaoshu Zhu Email: [email protected] Co-supervisor: Dr Sue Cochrane Email: [email protected] Campus/s project is offered and conducted: Campbelltown Background (200 words): Breast cancer is the second leading cause of cancer deaths in women today (World Health Oragnisation 2011). With the advances in medical knowledge, the survival rates for breast cancer have been improving for the past forty years; however the side effects of many conventional therapies in treating breast cancer are still harmful and distressing which decrease quality of life in patients and increase use of health care resources (Markes, Brockow et al. 2006). In the case of surgically induced lymphedema, there is no cure requiring daily management by compression and physical therapy. Skin reaction, radiodermatitis, occurs in nearly all patients who undergo radiotherapy which may delay or interrupt the treatment and can produce spontaneous bleeding, ulceration and necrosis. Many cancer patients or survivors use Chinese herbal medicine (CHM) for managing adverse effects from conventional therapies including lymphedema and radiodermatitis (Kremser, Evans et al. 2008). This project is part of a series of research studies in the field of TCM’s contribution to breast cancer. There has been a Honours project exploring any evidence of effectiveness on use of CHM on these two conditions through a systematic literature review with meta-analysis, findings and results will become available soon. Some preliminary findings indicate the need for the development of a clinical protocol. It is anticipated findings of this project will inform the design of a clinical trial and become the basis of future PhD study. Aim of Study: Design a clinical protocol on the use of CHM for lymphedema and radiodermatitis caused by local therapies in women with breast cancer Methods: Literature review, in-depth review with Delphi method on a small cohort of CHM oncologists in China and CHM practitioners in Australia. Ethics Application Requirements: Yes. Key References: Kremser, T., A. Evans, et al. (2008). "Use of complementary therapies by Australian women with breast

cancer." The Breast 17: 387-391. Markes, M., T. Brockow, et al. (2006). Exercise for women receiving adjuvant therapy for breast cancer,

Cochrane Database of Systematic Reviews, Issue 4. World Health Oragnisation. (2011). "Breast cancer awareness month." from

http://www.who.int/cancer/events/breast_cancer_month/en/.

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Honours projects offered at

Hawkesbury Campus

131

Title of Project: Comparative genomics and functional analysis of “stomatal movement genes” for barley salt tolerance Supervisor: Dr. Zhong-Hua Chen Email: [email protected] Co-supervisor: A/Prof. Paul Holford Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Campus Background (200 words): Stomatal guard cells regulate photosynthesis and control plant water loss and are, thus, fundamentally involved in determining crop yield. Three “stomatal movement genes” (guard cell slow and quick anion channel genes: SLAC1, SLAH3, and QUAC12) play key roles in regulating plant stress tolerance during the evolution and adaptation to extreme environmental conditions including soil salinity, a problem that is likely to increase due to climate change. Malting barley is one of Australia’s major agricultural export commodities, but its yield and quality can be reduced by soil salinity. Recently the barley genome has been sequenced and this is facilitating the exploration of genes that could be important for yield performance of Australian barley varieties under saline conditions. Aim of Study: Our hypothesis is that SLAC1, SLAH3, and QUAC12 have major roles in determining salt tolerance in barley by regulating stomatal movement. This proposed research project is firstly aimed at amplifying and sequencing these three barley genes for comparative genomic analysis. The second aim is to use molecular techniques to assess the expression of the three genes in stomata of both control and saline conditions. Methods: This experiment will employ molecular biological (PCR and qPCR) and physiological (stomatal imaging) techniques and comparative genomics (e.g. NCBI, phytozome database) to analyse the contribution of the three genes towards salt tolerance in Australian malt barley lines. Ethics Application Requirements: N/A Key References: Chen ZH, et al. (2007) Funct. Plant Biol. 34: 150–162 Dreyer et al. (2012) Frontier in Plant Science 3: 263 Eisenach C, et al. (2012) Plant J 69: 241-251 Hedrich R. (2012) Physiol. Rev. 92: 1777-1811 The International Barley Genome Sequencing Consortium (2012) Nature 491: 711–716 Zhou G, et al. (2012) Mol. Breeding 29:427–436

132

Title of Project: Carbon dioxide affected stomatal behaviour in Arabidopsis: a model system for predicting crop performance in the future climate Supervisor: Dr. Zhong-Hua Chen Email: [email protected] Co-supervisor: A/Prof. Paul Holford Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Campus Background (200 words): Human activities have caused an elevation of atmospheric CO2 levels. Levels are predicted to double in the 21st century and this change is one of our major global environmental issues. Rising atmospheric CO2 concentration is expected to increase global temperature and have unpredictable ecological and environmental consequences. Stomata are consisted of pairs of guard cells that regulate CO2 exchange for photosynthesis and control water loss. Stomata play a central role in sensing and responding to environmental signals such as light, CO2, temperature, humidity, and pollution. Generally, CO2 regulates stomatal movements by opening and closing the stomata at low and high CO2 concentrations, respectively. Transpirational water loss through stomata contributes to 70% of total agricultural water usage; thus climate change could have a major impact on crop production. Aim of Study: Understanding the mechanisms of high CO2 on stomatal guard cells will help to bridge the gaps between reducing agricultural water use and maintaining high crop yield. This project seeks to fill these gaps in knowledge by using Arabidopsis CO2 responsive mutants. In this project, you will investigate how stomata achieve a dynamic range of apertures at elevated CO2 concentrations and how these high concentrations affect the expression pattern of stomatal specific genes. Methods: The experiments will utilise a micro-imaging system for recording stomatal movement under elevated CO2. Molecular techniques, including q-PCR, will be used to follow changes in gene expression in response to high CO2. Ethics Application Requirements: Approved Key References: Chen ZH, et al. (2010) Plant J. 61: 816–825 Eisenach C, et al. (2012) Plant J 69: 241-251 Gray JE, et al. (2000) Nature 408: 713–716 Hashimoto M, et al. (2006) Nat. Cell Biol. 8: 391–397 Hetherington AM, Woodward FI (2003) Nature 424: 901–908 Hu H, et al. (2010) Nat. Cell Biol. 12: 87–93 Lee M, et al. (2008) Nat. Cell Biol. 10: 1217–1223 Negi J, et al. (2008) Nature 452: 483–486 Vahisalu T, et al. (2008) Nature 452: 487–491 Willmer C, Fricker M (1996) Stomata. Chapman & Hall, London Young JJ, et al. (2006) Proc. Natl. Acad. Sci. USA 103: 7506-7511

133

Title of Project: Predators and Prey – Plants, Animals and Interactions Contact: James Cook Email: [email protected] Telephone: 4570 1371

Contact: Oula Ghannoum Email: [email protected] Telephone: 4570 1581 Campus project is offered and conducted : Hawkesbury (Hawkesbury Institute for the Environment)

Background:

Plants, Animals and Interactions is one of three themes within the Hawkesbury Institute for the Environment. Select one of our ready-made projects from the list found at http://www.uws.edu.au/hie/scholarships/hie_honours_scholarships or develop your own with any one of the eleven active researchers in this field. The Hawkesbury Institute has the facilities, the people, and the enthusiasm to make honours projects challenging and rewarding for capable science undergraduates.

Aim of the Study:

Have you thought about:

- symbiosis and sex change in insects? - climate change impacts on Australia’s native plants? - how plants adapt to their environments?

The research team is focusing on how the abiotic environment, and in particular climate change, shapes the ecology and physiology of plants and animals. They also investigate how biotic interactions between species – plants, animals and microbes – underpin ecosystems and respond to environmental change. The team has particular expertise in the complementary areas of eco-physiology, evolutionary ecology and species interactions, and they pursue laboratory and field-based research, using both our unique experimental facilities and natural environmental gradients. The team study systems from the genomic and biochemical levels through to ecosystem-level responses to develop integrated understanding of both patterns and the underlying processes. This helps to predict and manage ecosystem functions and services across different types of landscapes, including natural woodlands, forest plantations and agricultural systems. Contact one of our theme leaders (above) or any researcher within this theme – contacts can be found directly on the theme’s website at http://www.uws.edu.au/hie/research/plants,_animals_and_interactions.

Methods:

The methods employed will depend on your project and what will most benefit you as a budding researcher. The Hawkesbury Institute has extensive field facilities, laboratories, glasshouses and equipment available including the recently established EucFACE field site. View some of our facilities at http://www.uws.edu.au/hie/facilities.

Ethics Application requirements:

Most projects will not require ethics clearance, but check this with your proposed supervisor.

Key References:

See below or refer to our extensive list of publications at http://www.uws.edu.au/hie/publications.

Aslam TJ, Johnson SN, Karley AJ, (2013) 'Plant-mediated effects of drought on aphid population structure and parasitoid attack', Journal of Applied Entomology, vol.137, no.1-2, pp 136-145

Franks PJ, Adams MA, Amthor JS, Barbour MM, Berry JA, Ellsworth DS, Farquhar GD, Ghannoum O, Lloyd J, McDowell N, Norby RJ, Tissue DT, von Caemmerer S, (2013) 'Sensitivity of plants to changing atmospheric CO2 concentration: From the geological past to the next century', New Phytologist, vol.197, no.4, pp 1077-1094

Wang H, Ridley J, Dunn DW, Wang R, Cook JM, Yu DW, (2013) 'Biased oviposition and biased survival together help resolve a fig-wasp conflict', Oikos, vol.122, no.4, pp 533-540

134

Title of Project: A Groundwater Management and Sustainability Project to Improve Livelihood of Village Communities in India Supervisor: Professor Basant Maheshwari Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Background (200 words): This project provides ideal opportunities to do an honours project about sustainability issues in village communities in India and be part of creating a positive community development scenario. As part of your involvement, you can work in any of the following aspects connected with the project:

• Work with the ACIAR project team to understand socio-economic, gender, equity and cultural issues that affect livelihood of people and identify barriers to community development and sustainability of natural resources in the study area;

• Participate in monitoring of groundwater use and other natural resources and work with villagers to develop some insights for situation improvement; and

• Work with local schools in the study area to develop a range of teaching materials and help students to learn about water, sustainability and livelihood issues around their villages and be part of sustainable future through education, capacity building, awareness and positive change in village communities.

Your involvement in the project will require working in the villages in the study area for up to 8 weeks to collect you field data. Some assistance towards your airfare for travel to India may be available. Your work will be supported by researchers of this ACIAR project and government agency staff associated with the project. Further, the ACIAR project team will assist you for local transport and accommodation in hostels during your stay. The honours student working on this project will be offered a scholarship of $4,000 for the duration of the study and will be paid travel expenses for field work in India. Aim of Study: The overall aim of this project is to improve the security of irrigation water supplies and enhance livelihood opportunities for rural communities. Specifically, the project will focus on assessing the effectiveness of current rainwater harvesting and groundwater recharge structures and demand management strategies at village scale. The project aims to develop or adapt suitable best practice guidelines and modelling and assessment tools that can be applied with relatively easily available local information. This study will be conducted in Sabarkantha district in Gujarat and Udaipur district in Rajasthan. Methods:

You will be part of team in the collection of a range of hydrologic, agronomic, economic, social and cultural data at selected clusters of villages. Depending upon your background and interest, your honours project will relate to the development of bio-physical / socio-economic tools and models to evaluate the current issues of surface water and groundwater management. Ethics Application Requirements: Yes

135

Title of Project: Sustainable Management of Stormwater and Wetlands for Securing Irrigation Water Supplies for Sporting Ovals and Parks in the Liverpool City Council Area Supervisor: Professor Basant Maheshwari Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Background (200 words): Because of current water shortages, population growth, greater expectations and possibly climate change, communities are moving to integrated water cycle management. Many urban open spaces in Australia rely fully or partially on potable water supplies for irrigation of sporting fields. The critical level of Sydney’s water supplies has reduced the availability of urban supplies to supplement irrigation in this region. In general there is increasing competition between urban supplies and peri-urban agricultural irrigation. There is a need to understand and evaluate key water management issues in the urban context for securing future water supplies. The honours student working on this project will be offered a scholarship of $4,000 for the duration of the study and will work closely with Liverpool City Council. Aim of Study: The main objectives of this project are as follow:

1. Monitor and evaluate the effectiveness wetlands for treatment of stormwater; 2. Assess the medium and long-term impacts of treated stormwater for irrigation of sporting

ovals on soil salinity, pH and turf health; 3. Identify strategies for improved management of wetlands systems for stormwater use; 4. Assess the current design and the maintenance requirement of the wetland system; and 5. Identify Opportunity for the current (or similar) system to be adopted for other areas of

Council.

Methods: • The quality of water (before and after the entry into the wetland system) will be assessed at

regular interval; • The quality of soil and turf will be monitored at a regular interval; • The effect of wetland system in improving water quality will be analysed and modelled to

understand the performance of wetlands; and

Ethics Application Requirements: None.

136

Title of Project: A Groundwater Management and Sustainability Project to Improve Livelihood of Village Communities in India Supervisor: Professor Basant Maheshwari Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Background (200 words): Stormwater in urban areas gets contaminated with a range of pollutants, and it can thus have a significant impact on water quality and health of local river systems. Tumblemate™ is a device that can remove a range of pollutants and other materials contained in stormwater. The device consists of integrated components to remove litter, hydrocarbons, coarse and fine sediments and colloids. The design of this device involved considerations to Australian Runoff Quality (ARQ) guidelines, average recurrence interval of rainfall, intensity-frequency-duration curves, durability and regular maintenance requirements and cost of installation. There appears considerable potential for this devise in regards to improved stormwater quality, reduced land area for treatment and reduced capital and ongoing maintenance costs. Another advantage over systems commonly in use is the incorporation of a dry sump to prevent pollutant mobilisation by degradation of stored litter and contaminated sediments. There are a number of opportunities for the use of this system, from meeting surface water quality objectives for water reuse at a regional, industrial or domestic scale. The honours student working on this project will be offered a scholarship of $4,000 for the duration of the study and will work in close collaboration with an industry partner. Aim of Study: The overall aim of this project is to analyse and model the performance a new and innovative Stormwater Decontamination Device (SDD) which incorporates a series of treatment methods that are usually undertaken separately to remove urban pollutant in stormwater. Methods: Research to be undertaken in this project will include simultaneous laboratory and in-situ (urban environment) water quality monitoring and refinement of SDD design under a range of climatic/ weather events and situations over the project period at the University of Western Sydney – Hawkesbury campus. The research will assist in commercialising the device and developing framework and modelling tool for field operation of the unit by stormwater managers in local government areas across Australia. Ethics Application Requirements: No.

137

Title of Project: Restoration of Cumberland Plain Woodland ground layer species Supervisor: Charles Morris Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Background (200 words): A joint experiment has been established between UWS and Greening Australia, to investigate techniques of restoring native plant ground layer species on degraded Cumberland Plain woodland sites. The experiment involves biomass removal techniques (slashing, burning), soil nutrient reduction by carbon addition, and seed addition, to see what combination of methods gives the best outcome. The treatments have been designed to address known barriers to restoration of native plant ground layer species; dense exotic grass canopies, elevated soil nutrient levels, and lack of plant seeds and propagules (Morris and de Barse 2013). The experiment has been established in 2013; this project would continue the experiment in 2014. Aim of Study: to assess the effectiveness of canopy removal, soil nutrient reduction and seed addition in restoration of native plant species to degraded Cumberland Plain woodland. Methods: the experiment itself has been established in 2013. Work in 2014 will entail:

- Botanical survey of plots (summer, winter, spring) to assess the longer term effects of the treatments on native and exotic plant composition

- Application of carbon to the soil to reduce soil nitrate - Measurement of soil nutrient levels, particularly nitrate, to assess the effectiveness of treatments

in reducing soil nitrate

Ethics Application Requirements: nil Key References: Morris, EC & de Barse, M (2013) Carbon, fire and seed addition favour native over exotic species in a grassy woodland. Austral Ecology 38, 403 – 426.

138

Title of Project: Restoration of Cumberland Plain Woodlands: impacts on soil fauna and ecosystem functioning Supervisor: Dr Uffe Nielsen Email: [email protected] Co-supervisor: TBD Email: Campus/s project is offered and conducted: Hawkesbury Background (200 words): Cumberland Plain woodlands (CPW) supports critically endangered ecological communities, but has been impacted by anthropogenic land use changes. Ongoing efforts to restore CPWs exist but the success of these endeavours is complicated by the intricate links between the plants aboveground and soil organisms belowground. In particular, soil organisms are vital to ecosystem functions, such as nutrient availability and decomposition, and restoring functional belowground communities is therefore essential for long term success of these ecosystems. However, knowledge of belowground communities in CPWs is virtually non-existing particularly in relation to the effects of restoration efforts. Through this project we will gain critical knowledge of the impact of restoration on belowground communities and how this influences ecosystem functioning. However, students are encouraged to contact the supervisors to discuss other potential projects. Aim of Study: The aim of this study is to determine if current practices used to restore plant communities have similar positive effects belowground. In particular, the study will determine if soil mites or nematode communities are successfully restored, i.e. are the communities found in restored sites similar to those in pristine CPWs, and whether the restoration of these communities lead to increased functioning (nutrient availability, decomposition). Methods: The project can incorporate a range of methods. We will collect soil samples from multiple CPWs ranging from pristine sites to restored sites to assess soil properties and belowground communities (either soil mites or nematodes; other groups could also be considered). We will also assess ecosystem function at these sites (nutrient availability, decomposition) and link this to the state of the belowground communities. The student will help guide the project and determine what we should and shouldn’t do. Ethics Application Requirements: None Key References:

Bardgett, R.D. 2005. The Biology of Soil: a community and ecosystem approach. Oxford University Press.

139

Title of Project: Can ectomycorrhizal fungi moderate the impacts of plant parasitic nematodes on trees? Supervisor: Dr Uffe Nielsen Email: [email protected] Co-supervisor: Jonathan Plett Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Background (200 words): Australia holds an amazing natural abundance and diversity of living organisms, but this diversity is threatened by human activities and invasive species. For example, it is estimated that Cumberland Plain Woodlands (CPW) once covered more than 125,000 hectares of land in the Sydney basin but now less than 9% of the original woodlands remain intact. Therefore, CPWs are listed as endangered by the NSW Threatened Species Conservation Act 1995 and the Commonwealth Environment Protection and Biodiversity Conservation Act 1999. This project will contribute toward developing a feasible way to protect, and promote the recovery of degraded, Australian ecosystems including CPWs. The research will focus on the relationship between plants and ectomycorrhizal (ECM) fungi. It is well known that these fungi help plants acquire nutrients from the soil and that this influence the competition between plant species. However, there is also evidence that suggest that ECM fungi can protect plants from, or at least minimize the impact of, plant parasitic nematodes. This may be used to help prevent invasive species incursion into native woodland habitat. Students are encouraged to contact the supervisors to discuss other potential projects. Aim of Study: The project aims to determine if the presence of ECM fungi on the roots of native Cumberland Plain Woodland trees suppress plant parasitic nematodes, and/or forces plant parasitic nematodes to favour parasitism of invasive plant species that cannot form a symbiotic relationship with this class of fungi, under ambient climatic conditions as well as elevated levels of carbon dioxide and temperature. Methods: The student will 1) establish lab and pot experiments to test whether plant parasitic nematodes help native mycorrhizal host trees (e.g. Eucalyptus) compete against invasive non-ectomycorrhizal plants (e.g. African Olive) when grown individually or together under ambient and elevated carbon dioxide concentration and/or temperature, and 2) identify one or more novel compounds expressed by either host plants or ectomycorrhizal fungi that deter nematode predation of tree roots. Ethics Application Requirements: None Key References: Lijbert Brussaard L, Kuyper TW & de Goede RGM (2001) On the relationships between nematodes, mycorrhizal fungi and plants: functional composition of species and plant performance. Plant and Soil 232: 155–165

140

Title of Project: Native and exotic bioengineers in a changing climate Supervisor: Associate Professor Pauline Ross Email: [email protected] Co-supervisor: Dr Victoria Cole Email: [email protected] Campus/s project is offered and conducted: UWS Hawkesbury and Sydney Institute of Marine Science (SIMS) Background (200 words): Biodiversity is being lost due to climate change and other anthropogenic stressors. One approach to conserving biodiversity may be to protect bioengineers (Wright & Jones 2006). Bioengineers are species that have a disproportionately large influence on biodiversity because they modify the environment experienced by other organisms (Wright & Jones 2006). Mussels are key bioengineers of coastal habitats (Gutiérrez et al. 2003). Mussels support dense and diverse biological communities by providing substratum for attachment, concentrating food resources and providing protection from predators (Cole 2010, Cole & McQuaid 2010). The combination of climate change and the introduction of numerous exotic species into NSW’s coastal waters further threatens native biodiversity. It is, however, not fully known how climate change will affect the impacts of exotic species in their introduced ranges. The Mediterranean mussel, Mytilus galloprovincialis, is listed in the top 100 of the world’s worst invaders by the International Union for Conservation of Nature. Using novel field experiments, ocean warming will be manipulated in Sydney Harbour. The response of organisms reliant on the habitat created by the introduced mussel, M. galloprovincialis, will be compared to those associated with the native mussel, Trichomya hirsuta. Aim of Study: The primary aim of the project is to determine the role of native and introduced mussels as providers of habitat to coastal biodiversity in a changing climate. Specifically, the hypotheses that will be tested are: (i) Assemblages associated with the native mussel will differ from those associated with the exotic mussel; (ii) Assemblages associated with mussels in experimentally heated water will differ from those associated with mussels in ambient temperature water; (iii) The response of assemblages to temperature will be dependent on the species of mussel. Methods: Mytilus galloprovincialis and Trichomya hirsuta co-occur in Sydney Harbour. This field experiment will be done at near the mouth of the harbour at Sydney Institute of Marine Science (SIMS), Chowder Bay. The water temperature will be experimentally increased to match that predicted for 2100 using the “hot-plate” system designed by Smale et al. (2011). Monocultures of either M. galloprovincialis or T. hirsuta will be deployed over plates which are warmed or at ambient temperature for 6 weeks. After assemblages of macrofauna have colonised the mussel beds, 10 cm cores from each hotplate will be sampled. All samples will be examined in the laboratory and invertebrates retained on a 500 µm sieve will be sorted and enumerated by species. Ethics Application Requirements: N/A Key References: Cole V.J. 2010. Alteration of the configuration of bioengineers affects associated taxa. Marine Ecology Progress Series 416:127-

136. Cole V.J., McQuaid C.D. 2010. Bioengineers and their associated fauna respond differently to the effects of biogeography and

upwelling. Ecology 91:3549-3562. Gutiérrez J.L., Jones C.G., Strayer D.L., Iribarne O.O. 2003. Mollusks as ecosystem engineers: the role of shell production in aquatic

habitats. Oikos 101:79-90. Smale D.A., Wernberg T., Peck L.S., Barnes D.K.A. 2011. Turning on the Heat: Ecological Response to Simulated Warming in the

Sea. PLoS ONE 6: e16050 Smale D.A., Wernberg T. 2012. Short-term in situ warming influences early development of sessile assemblages. Marine Ecology

Progress Series 453:129-136. Wright J.P., Jones CG. 2006. The concept of organisms as ecosystem engineers ten years on: progress, limitations, and challenges.

Bioscience 56:203-209.

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Title of Project: Climate change and the early development of native and exotic mussels Supervisor: Associate Professor Pauline Ross Email: [email protected] Co-supervisor: Dr Victoria Cole Email: [email protected] Campus/s project is offered and conducted: UWS Hawkesbury and Sydney Institute of Marine Science (SIMS) Background (200 words): The Intergovernmental Panel on Climate Change predicts that temperature and concentration of CO2 will increase under future climate change scenarios. Together, temperature may act synergistically with elevated CO2 to exacerbate negative responses on the early developmental stages (Parker et al. 2009). We know little about how calcifying invertebrates will respond to the synergistic impact of temperature and CO2 increase in Sydney Harbour. The combination of climate change and the introduction of numerous exotic species into NSW’s coastal waters further threaten native biodiversity. It is, however, not fully known how climate change will affect the impacts of exotic species in their introduced ranges. The introduced mussel, Mytilus galloprovincialis, is listed by the IUCN as one of the world’s worst 100 invaders. Although, introduced species are often highly plastic in their ability to deal with new environments, Parker et al. (2010) found that the native Sydney Rock oyster was able to adapt to increases in pCO2 whereas the introduce Pacific Oyster could not. Mytilus galloprovincialis co-occurs in Sydney Harbour with the native mussel Trichomya hirsuta. Experiments will determine whether the native or introduced mussel will be better placed under future climate change scenarios. Aim of Study: The primary aim of this study is to determine whether introduced or native mussels will fare better under future climate change in terms of increasing temperatures and pCO2. Although we cannot predict which species will do better, the specific hypothesis to be tested with this study is: Larval development of each will be negatively impacted by synergistic effects of CO2 and temperature. Methods: Experiments will be done using adult populations of T. hirsuta and M. galloprovincalis from Sydney Harbour. For each species, a minimum of 10 males and 10 females will be spawned, and the eggs will be fertilised and maintained under current and future temperature and pCO2. Two levels of pCO2 will be obtained by bubbling CO2 into filtered seawater, a current atmospheric level of 380 μatm pHNBS 8.19-8.20, and an elevated atmospheric level pCO2 level predicted for 2100 of 856 μatm pHNBS 7.89-7.90 (Parker et al. 2012). Using an orthogonal design, temperature will also be manipulated, with the current temperature of 24°C and the predicted temperature for 2100 of 30°C. Fertilisation success, time to each stage of development of larvae, and survival of larvae will be monitored over 10 days.

Ethics Application Requirements: N/A Key References: Parker L.M., Ross P.M., O’Connor W.A. 2009. The effect of ocean acidification and temperature on the

fertilization and embryonic development of the Sydney rock oyster Saccostrea glomerata (Gould 1850). Global Change Biology 15:2123-2136.

Parker L.M., Ross P.M., O’Connor W.A., Borysko L., Raftos D.A., Pörtner, H.O. 2012 Adult exposure influences offspring response to ocean acidification in oysters. Global Change Biology 18: 82-92.

Parker L.M., Ross P.M., O’Connor W.A. 2010. Comparing the effect of elevated pCO2 and temperature on the fertilization and early development of two species of oysters. Marine Biology 157:2435-2452.

Ross P.M., Parker L., O’Connor W.A., Bailey E.A. 2011. The impact of ocean acidification on reproduction, early development and settlement of marine organisms. Water 3:1005-1030.

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Title of Project: Evaluating teaching: beyond student evaluations Supervisor: Associate Professor Pauline Ross Email: [email protected] Co-supervisor: Prof Philip Poronnik Email: [email protected] Campus/s project is offered and conducted: UWS Hawkesbury and University of Sydney Background (200 words): For the past few years, there has been global interest in academic quality and the development of valid indicators of learning. Student satisfaction and employment have been used to date as proxies for determining the quality of graduates (Deane and Krause 2012). At the same time there has been a discourse of concern about the quality of science teaching at all levels of education. World leaders and Nobel scientists are now saying that for science to continue its progress in the 21st century, it must be backed by high-quality science education at all levels (Weiman 2007; Weiman et al. 2010; Chubb 2012; Obama 2013). The question arises what does high quality science education look like, especially at the tertiary level? We can evaluate teaching quality at least in principle by measuring student learning outcomes (Weiman and Gilbert in press), but to do this requires validation processes with instruments which can be difficult to implement and take time to develop. We can also evaluate teaching quality by measuring teaching practices, both the inputs (in class course and supporting information) and the process (assessment, feedback and grading). At the University of British Columbia, a teaching practice survey has been developed and validated by the Noble Laureate, Carl Weiman, to determine the quality of teaching of science at the tertiary level. The development of this survey instrument presents a unique opportunity for a student to evaluate tertiary teaching quality in the sciences. This project would suit a student interested in potentially pursuing a career related to teaching and learning and an honours in science education. Aim of Study: To evaluate the quality of the teaching of science at universities in Australia. Methods: The University of British Columbia, through the Carl Weiman Science Education Initiative has developed a “Teaching Practices Survey for the faculty of Science”. This survey will be used to assess the quality of teaching practices in science throughout selected universities and science faculties in Australia. Ethics Application Requirements: Human Ethics required and is currently in progress Key References: Chubb, I. 2012. Office of the Chief Scientist. Health of Australian Science. Australian Government Canberra. 212 pages. Deane, E. and Krause, KL. 2012. Towards a Learning Standards Framework. Learning and Teaching Standards (LaTS) Project: Peer review and moderation in the disciplines. http://www.uws.edu.au/__data/assets/pdf_file/0010/398620/Learning_Stds_Framewk_Final_Dec_2012.pdf Obama, B. 2013. President Obama Speech to the National Academy of Science. http://notes.nap.edu/2013/04/30/president-barack-obamas-speech-to-the-national-academy-of-sciences-full-transcript/ Accessed 2 June 2013. Schmidt, B. 2012. Brian Schmidt: in conversation. 26th July 2012. The Conversation http://theconversation.com/brian-schmidt-in-conversation-8383Accessed 2 June 2013. Weiman, C.O. 2007. Why not try a scientific approach to science education? Change Sept/October pp 9–15. Weiman, C., Perkins, K. and Gilbert, S. 2010. Transforming science education at large research universities: A case study in Progress. Change Mar/April 1-11. Weiman, C. and Gilbert, S. in press The teaching practices survey: a new tool for the evaluation and improvement of college and university teaching in mathematics and science.

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Title of Project: Shifting laboratory experiments on climate change into Sydney Harbour Supervisor: Associate Professor Pauline Ross Email: [email protected] Co-supervisor: Dr Victoria Cole Email: [email protected] Campus/s project is offered and conducted: UWS Hawkesbury and Sydney Institute of Marine Science (SIMS) Background (200 words): Climate change, in the form of warming and acidifying oceans, represents growing threats to marine species. This is concerning given the east Australian coastline is a “climate changed hotspot”. Rising temperatures will test the physiological limits of many species and increasing pCO2 has consequences for many marine species, particularly those with calcified structures (Ross et al., 2011, Parker et al., 2012). The diverse assemblages of plants and animals living in Sydney Harbour are vital in maintaining the health of the harbour and in supporting marine biodiversity. Many species are filter-feeders and are important in maintaining clarity of coastal waters. Future changes to the climate may, however, affect the efficiency of filter-feeders and overall ecological functioning of the harbour. Research will focus on the ecological functioning of key filter-feeding taxa (e.g. bivalves, tubeworms, barnacles, sea-squirts) living on man-made structures (e.g. pontoons, pilings) in Sydney Harbour. Most studies simulating climate change on the marine environment are in the laboratory, but it is well known that this may not replicate the situation in the field. Through a series of novel field experiments, it will be determined how key species will perform under future climate change (climate warming and ocean acidification). Aim of Study: The study aims to answer the key question: Will climate warming and ocean acidification affect the ecological functioning (in terms of filtration) of key filter-feeding species in Sydney Harbour? The study will specifically test the hypothesis that under future climate change scenarios (increased pCO2 and temperature), rates of filtration of the key species will decrease. Methods: Three key filter-feeding species (e.g. the mussel Mytilus galloprovincialis, the barnacle Balanus amphitrite, and the tubeworm Hydroides elegans) commonly found in Sydney Harbour will be selected (Cole et al. 2005). This field experiment will be done at near the mouth of the harbour at the Sydney Institute of Marine Science (SIMS),Chowder Bay. The water temperature will be experimentally increased to match that predicted for 2100 using the “hot-plate” system designed by Smale et al. (2011). Monocultures of adults of each of the three species will be deployed over plates which are warmed or at ambient temperature for 1 month. In enclosed chambers, two levels of pCO2 will be obtained by bubbling CO2 into filtered seawater, a current atmospheric level of 380 μatm pHNBS 8.19-8.20, and an elevated atmospheric level pCO2 level predicted for 2100 of 856 μatm pHNBS 7.89-7.90 (Parker et al. 2012). Using an orthogonal design, the effects of each of the factors (temperature and pCO2) and their interactive effects on the feeding rates of filter-feeders will be investigated. Feeding rates of the key species will be measured in the field, using previously developed novel methods (Cole et al. in progress). Based on these methods, small patches (e.g. ≈15 adult mussels) will be enclosed in containers will be secured to the substratum. Each container will have a set volume of unfiltered seawater. Filtration chambers will be placed over the assemblages that are at ambient or experimentally warmed temperatures. For those that required increased concentrations of CO2, it will be bubbled into the sealed containers. 100 mL of water will be sampled from each container with a syringe at the beginning of the experiment and also after 1 hour. Samples will be fixed with glutaraldehyde, frozen at -4°C, and defrosted in a 38°C waterbath. Using a particle counter at SIMS, the filtration rates will be determined. Ethics Application Requirements: N/A

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Key References: Cole V.J., Glasby T.M., Holloway M.G. 2005. Extending the generality of ecological models to artificial

floating habitats. Marine Environmental Research 60:195-210. Parker L.M., Ross P.M., O’Connor W.A. 2009. The effect of ocean acidification and temperature on the

fertilization and embryonic development of the Sydney rock oyster Saccostrea glomerata (Gould 1850). Global Change Biology 15:2123-2136.

Parker L.M., Ross P.M., O’Connor W.A. 2010. Comparing the effect of elevated pCO2 and temperature on the fertilization and early development of two species of oysters. Marine Biology 157:2435-2452.

Parker L.M., Ross P.M., O’Connor W.A., Borysko L., Raftos D.A., Pörtner, H.O. 2012 Adult exposure influences offspring response to ocean acidification in oysters. Global Change Biology 18: 82-92.

Ross P.M., Parker L., O’Connor W.A., Bailey E.A. 2011. The impact of ocean acidification on reproduction, early development and settlement of marine organisms. Water 3:1005-1030.

Smale D.A., Wernberg T., Peck L.S., Barnes D.K.A. 2011. Turning on the Heat: Ecological Response to Simulated Warming in the Sea. PLoS ONE 6: e16050

Smale D.A., Wernberg T. 2012. Short-term in situ warming influences early development of sessile assemblages. Marine Ecology Progress Series 453:129-136.

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Title of Project: Coral fluorescent proteins as light inducible electron transporters Supervisor: Dr Anya Salih Email: [email protected] Co-supervisors: Dr Paul Smith, UWS and Dr Robert Campbell, University of Edinburgh Campus/s project is offered and conducted: Hawkesbury Campus Background: A diverse family of multi-coloured proteins related to the well-known green fluorescent protein (GFP) colour tissues of reef building corals and many other cnidarians. The biological function of these proteins is still a mystery, although an increasing body of work indicates that they are involved in coral photobiology (e.g., Salih et al. Nature, 2000). GFPs of different colours from marine organisms, including corals, are widely used as genetic markers in live cell biology and biomedical research. The rapid explosion of GFP-based applications culminated in the 2008 Nobel Prize in Chemistry awarded to researchers involved in the discovery and development of GFPs. Novel GFPs with different colours and properties are in great demand and Great Barrier Reef corals can provide a new resource for new types that can be developed into new bioimaging labels and biosensors (e.g., Matz et al. Nature Biotechnology, 1999; Salih, 2012). Recently, a discovery was made that upon exposure to light certain GFP-type proteins can donate electrons to biological electron acceptors (Bogdanov et al. 2009, Nature Chem. Biol.). In the presence of biologically relevant electron donating or accepting molecules in mammalian cells, GFP turned red after brief irradiation. The discovery of the electron transfer properties of certain coral GFPs poses an exciting possibility that the primary function of GFPs is in photoreduction — the light-prompted passing of electrons, and was referred to as the discovery of ‘animal photosythesis’ by publications in the media. If confirmed, the electron transfer function of these proteins has a major importance in coral biology and in a wide-range of biotechnological applications. Aim of Study: In this project, the electron transfer processes will be investigated in the newly cloned and purified GFP-type proteins isolated from the Great Barrier Reef corals as well as those occurring naturally in live coral, and transfected into bacterial and mammalian cells. Methods: The project will use confocal microscopy and microspectropic techniques at the UWS Confocal Bio-Imaging Facility, recombinant fluorescent proteins cloned by Salih and bacterial and mammalian cell culture facilities in laboratories at Hawkesbury or Campbeltown. Reef corals will be maintained in the Coral Reef Aquaria facility at UWS Hawkesbury Campus. Ethics Application Requirements: Not required Key References: A M Bogdanov et al. (2009) Green fluorescent proteins are light-induced electron donors. Nature Chem Biol. 26: 5(7), 459–461. M V Matz et al. (1999) Fluorescent proteins from nonbioluminescent Anthozoa species. Nature Biotechnol, 17, 969–973. A Salih et al. (2000) Fluorescent pigments in corals are photoprotective. Nature, 408: 850–853. A Salih (2012) Fluorescence control in natural green fluorescent protein (GFP)-based photonic structures of reef corals. Optical Biomimetics: Materials and Applications, Woodhead Publ. UK. p. 199-228.

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Title of Project: Function of coral tissue colours in light modulation of host–plant symbiosis Supervisor: Dr Anya Salih Email: [email protected] Co-supervisors: Professor AWD Larkum, UTS & University of Sydney, and Dr Dimitri Deheyn, Scripps Institution of Oceanography University of California, San Diego Campus/s project is offered and conducted: Hawkesbury Campus Background (200 words): Reef corals, anemones and many other symbiotic cnidarians are brightly coloured by GFP-type pigments. These proteins emit light spanning almost the whole of the visible spectrum, from blue to red. In shallow waters GFP-type proteins are photoprotective and their expression is induced by sunlight. The mechanism of photoprotection involves many biological, biophysical and molecular processes that function to optimise the photosynthesis of symbiotic microalgae that live intra-cellularly in coral tissues. Corals depend on photosynthetically products produced by the microalgae but when photosynthesis is inhibited by high solar radiation or seawater warming, the resultant build-up of oxidative stress can harm and kill the coral host. Corals have evolved to be a highly efficient and dynamic photonic system to optimise and regulate sunlight. These processes play an important role in the photobiology and survival of corals but the different functions of variously coloured proteins are still poorly understood. Aim of Study: The project will investigate how different solar intensities and different wavelengths (UV, blue, green, red) influence the expression levels of colour proteins in coral tissues and how these modulate the internal light fields to optimise photosynthesis of endosymbiotic microalgae. Methods: Specific UV and visible light wavelengths can cause up- or down-regulation of certain GFP-type proteins, while others can spontaneously change colours. Cellular GFP-type protein expression will be studied by a range of advance optical techniques including optical microsensors to analyse light scattering, absorption and fluorescent properties of tissues as well as by confocal microscopy at the Confocal Bio-Imaging Facility. The photobiological experimental manipulations will be done using reef corals at the Coral Aquaria facility at UWS Hawkesbury Campus and Heron Island Research station on Great Barrier Reef. Microalgal photosynthetic responses will be determined by analysing chlorophyll fluorescence by pulse amplitude modulation (PAM) fluorometry and fluorescence lifetime microscopy (FLIM). Ethics Application Requirements: None required Key References: A Salih, AWD Larkum, G Cox, M Kühl & O Hoegh-Guldberg (2000) Fluorescent pigments in corals are photoprotective. Nature 408, 850-853. EG, Smith, C D’Angelo, A Salih & J Wiedenmann (2013) Screening by coral GFP-like chromoproteins supports a role in photoprotection of the zooxanthellae. Coral Reefs, 1-12. MS Roth, DD Deheyn (2013) Effects of cold stress and hot stress on coral fluorescence in reef-building corals. Science Report 3: 1421-1428.

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Title of Project: Light induced dynamic ion flux responses of coral-algal symbiosis Supervisor: Dr Anya Salih Email: [email protected] Co-supervisors: Dr Paul Smith [email protected] and Dr Zhonghua Chen [email protected] Campus/s project is offered and conducted: Hawkesbury Campus Background (200 words): Nature has produced a dazzling array of outstanding optical and molecular properties of green fluorescent proteins (GFPs) and a variety of biological functions that have only become apparent in the last decade. The biological function of GFPs in influencing ion flux in marine organisms has only been speculated upon, with studies indicating that GFPs may function as portable proton pumps within cnidarian cell cytoplasm. If shown to be biologically relevant, proton pumping by GFPs may perform diverse biological functions in marine organisms - from photosensing, chemosensing, to production of ATP from sunlight and in coral calcification. If direct proton pumping does not occur, then GFPs may be involved indirectly, by influencing cellular ion flux via light modulation of photosynthetic microalgae whose photosynthesis dynamically alters intracellular pH and ion flux. Aim of Study: The project will investigate the capacity of GFPs to alter H+ flux and pH in response to light using protein and hydrogel formulations and live GFP-pigmented coral cells with and without symbiotic microalgae. Methods: Changes in H+ flux and pH will be analysed using pH-sensitive dye SNARF-1 by confocal microscopy, microspectroscopy and fluorescence lifetime microscopy (FLIM) at the Confocal Bio-Imaging Facility. Rates of ion flux and pH change in response to different light intensities and wavelengths will be also studied in the electrophysiology laboratory using non-invasive ion flux microelectrodes. Light microfields in coral tissues will be analysed by miro-optical sensors connected to portable OceanOptics spectrometer. Controlled light experimental manipulations of cells and tissues will be done using reef corals maintained at the Coral Aquaria facility at UWS Hawkesbury Campus. Ethics Application Requirements: None required Key References: J Laurent, S Tambutte, E Tambutte, D Allemande & A Venn (2013) The influence of photosynthesis on host intracellular pH in scleractinian corals. J Experimental Biology, 216: 1398-1404. SR Meech S R (2009) Proton transfer – excited state reactions in fluorescent protein. Chem. Soc. Rev. 38: 2922–2934. A Salih (2012) Fluorescence control in natural green fluorescent protein (GFP)-based photonic structures of reef corals. Optical Biomimetics: Materials and Applications, Woodhead Publ. UK. p. 199-228.

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Title of Project: Cellular research of colour pigments in corals from Kimberley, Western Australia. Supervisor: Dr Anya Salih Email: [email protected] Co-supervisors: Dr Zoe Richards, Western Australian Museum Campus/s project is offered and conducted: Hawkesbury Campus Background (200 words): One of the least explored regions of shallow-water reef corals is the Kimberley in north-west Australia. Unusual coral communities have evolved to survive the renowned huge tidal exchanges up to 11 m, high solar radiation, frequent cyclones and high seawater temperatures of Kimberley reefs. Dr Zoe Richards from the Western Australian Museum has been researching the biodiversity of coral reefs of this frontier region and in collaboration with Dr Salih in UWS began a study of some of the unusual colourful pigments discovered in Kimberley corals. The pigments studied at the Western Australian museum include the bright red and other coloured pigments belonging to the fluorescent GFP-type protein group as well as the bright red pigments such as carotenoids, which give the orange colour to carrots and cooked lobsters. Carotenoids occur naturally in plants and corals may assimilate them by feeding on phytoplankton. The pigments may function in light absorption to maximize the potential for photosynthesis by symbiotic dinoflagellates and may help protect them from photo damage.. Aim of Study: The project will investigate selected traits that influence the high solar and thermo-tolerance of Kimberley corals, focussing on colourful pigments and other tissue based photoactive molecules. Methods: Coral samples sourced from Kimberley reefs will be send to the UWS Confocal Bio-Imaging facility where their optical and cellular properties will be investigated using confocal microimaging, spectroscopy and microsensors. Controlled light experimental manipulations of cells and tissues will be done using reef corals maintained at the Coral Aquaria facility at UWS Hawkesbury Campus. Ethics Application Requirements: None required Key References: ZT Richards, M Bryce, C Bryce (2013) New Records of Atypical Coral Reef Habitat in the Kimberley, Australia. Journal of Marine Biology. Volume 2013, Article ID 363894. See more at: http://australianmuseum.net.au/staff/zoe-richards#sthash.PVydiYLt.dpuf

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Title of Project: Cellular mechanisms involved in coral stress responses to climate change Supervisor: Dr Anya Salih Email: [email protected] Co-supervisor: Dimitri Deheyn, Scripps Institution of Oceanography University of California, San Diego Email: [email protected] Campus/s project is offered and conducted: Hawkesbury Campus Background (200 words): Around the world, reef corals are threatened by mass coral bleaching and resultant mortalities due to increasing seawater temperature related to global climatic changes. Mass bleaching occurs when the symbiotic microalgae living in coral tissues are expelled or are degraded as a result of an increase in cellular oxidative stress from the build-up of oxygen radicals in coral and microalgal cells. Recent assessments of the world’s reefs showed that nearly 30% have been lost largely due to climate-related mass coral bleaching and that these losses will continue to increase. In order to understand stress responses, tolerance thresholds and adaptive capacity of corals to survive climate change, it is important to understand the cellular processes involved. Cellular mechanisms that cause coral-symbiont dissociation and cell death include apoptosis and necrosis but are still not well understood. Increasingly, it is being recognized that corals have tissue defences that reduce the impact of bleaching. Fluorescent proteins reduce stress by sunscreening, can function as antioxidants and are important defences against bleaching stress. Aim of Study: The project will investigate cellular mechanisms of bleaching in corals exposed to elevated temperature under different conditions of oxidative stress in fluorescent and non-fluorescent corals. Methods: Experimental manipulations of live corals transported from the Great Barrier Reef and exposed to elevated temperature and oxidative stress will be conducted in UWS Coral Aquaria facility at Hawkesbury. Cellular stress response mechanisms will be studied by using live-cell confocal imaging and a range of cellular fluorescent stains specific for DNA, cytoskeleton, apoptosis, necrosis and oxidative stress at the UWS Confocal Bio-Imaging Facility. Other techniques will involve antioxidant assays, optical probes and microspectroscopy to characterise fluorescent proteins of different colours, pulse amplitude modulation fluorometry and fluorescence lifetime microscopy (FLIM) to analyse photosynthetic responses of symbionts. Ethics Application Requirements: Not required Key References: AH Baird, RT Bhagooli, PJ Ralph, S Takahashi (2009) Coral bleaching: the role of the host. Trends in Ecology & Evolution, 24: 1, 16-20. Roth MS, Deheyn DD (2013) Effects of cold stress and hot stress on coral fluorescence in reef-building corals. Sci Rep 3: 1421 A Salih, AWD Larkum, G Cox, M Kühl & O. Hoegh-Guldberg (2000) Fluorescent pigments in corals are photoprotective. Nature 408, 850-853.

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Title of Project: High Density Titanium Dioxide for Solar Applications Supervisor: Dr Leigh Sheppard Email: [email protected] Co-supervisor: Dr Marta Bello Lamo Email: [email protected] Co-supervisor: Dr Richard Wuhrer Email: [email protected] Campus/s project is offered and conducted: Hawkesbury and Parramatta Background (200 words): Titanium dioxide, TiO2, has emerged as an important material for the efficient harvesting of solar energy for alternative fuel generation (hydrogen) and water decontamination. This is due to its photosensitivity, outstanding corrosion resistance, and low cost. However, TiO2 also exhibits a broad range of functional properties of which not all are favourable for solar energy conversion. The Solar Energy Technologies research group seeks to understand how the properties of TiO2 can be tailored for best practical performance through the appropriate control of fundamental processing parameters. Aim of Study: This project is aimed at establishing a processing route that yields highly dense TiO2 from loose TiO2 powder. This will be achieved by investigating the influence of controlled processing variables, such as temperature, gas phase composition and time, on the microstructure of TiO2 powder compacts. Methods: Students undertaking this project will learn about the development of advanced ceramics and their engineering for solar applications. Students will also gain experience and skills with the use of advanced instrumentation for materials characterisation, particularly scanning electron microscopy and x-ray diffraction, in addition to the tools associated with the forming and fabrication of oxide-based semiconductors. Ethics Application Requirements: Nil Key References: L. Sheppard and J. Nowotny, “Materials for Photoelectrochemical Energy Conversion”, Advances in Applied Ceramics, 106 (2007) 9-20

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Title of Project: Novel Semiconducting Thin Films for Solar Applications Supervisor: Dr Leigh Sheppard Email: [email protected] Co-supervisor: Dr Marta Bello Lamo Email: [email protected] Co-supervisor: Dr Richard Wuhrer Email: [email protected] Campus/s project is offered and conducted: Hawkesbury and Parramatta Background (200 words): Titanium dioxide, TiO2, has emerged as an important material for the efficient harvesting of solar energy for alternative fuel (hydrogen) generation and water decontamination. This is due to its photosensitivity, outstanding corrosion resistance, and low cost. However, TiO2 also exhibits a broad range of functional properties, of which not all are favourable for energy conversion. The Solar Energy Technologies research group seeks to understand how the properties of TiO2 can be tailored for best practical performance through the appropriate control of processing parameters. Aim of Study: This project is aimed at establishing a deposition protocol for the preparation of doped TiO2 thin films that exhibit high sensitivity to sunlight. Using reactive magnetron sputtering, an advanced technique for the deposition of thin film semiconductors, Ti, O2 and various light-sensitive elements will be combined to form a novel TiO2-based compounds that is sensitive to the visible portion of the solar spectrum. Methods: Students undertaking this project will learn about the fabrication of advanced thin film materials using reactive magnetron sputtering. They will also gain experience with the use of advanced instrumentation for materials characterisation, including scanning electron microscopy and x-ray diffraction. Ethics Application Requirements: Nil Key References: L. Sheppard and J. Nowotny, “Materials for Photoelectrochemical Energy Conversion”, Advances in Applied Ceramics, 106 (2007) 9-20

152

Title of the project: Starch digestibility and glycemic behavior of major South Asian diets Supervisor: Ashok K Shrestha, PhD Email: [email protected] Co-supervisor: TBA Campus project is offered and conducted: Hawkesbury or Parramatta campus Background: Diabetes, Type 2, previously regarded as a disease of affluent has now threatened the health and economies of all nations. There are now close to 300 million diabetes in the world, Asia host 60% of them. India alone reported to have 61 million diabetic people and predicted to reach 100 million diabetic by 2030. This disproportionate rise in diabetes in South Asia has been blamed to the sedentary life-style, poor diet (ingredient) choice and obesity. The traditional diets eaten in Indian subcontinent are mostly carbohydrate based as meat, fish and eggs are sparingly eaten due to affordability, religious reasons or simply due to dietary habits. Recent economic revolution in India showed urban populations eat less of the traditional foods and lots of calories come from fats, animal foods, refined foods and high volume of sweets. Rice and wheat based foods are staple diet followed by tubers, legumes etc. In vitro digestibility study showed rice varieties are highly digestible1. Even among the Indian population, the perception of their traditional foods is not encouraging, such as, ‘Asian people are getting a lot of diseases, like diabetes, because of what we’re eating. The doctors have said ‘‘it’s what you are eating that is causing you to have so many diseases’. Glycemic index (GI) and glycemic loads (GL) are two major indicators of how much sugars are loaded in the body, after ingesting foods. Most of the processed foods, breakfast cereals in particular are heavily loaded with sugars and are rapidly absorbed in the body. Aim of the Study: The aim of this project is to study the digestibility and glycemic behaviour as well as physicochemical properties of commonly eaten (staple) South Asian diets that influence the rate of glucose release. The outcome of the study will link to potential impact on the glycemic health of the people in South Asian region. Methods: This study will perform digestibility studies on both the raw and cooked foods and characterize the physicochemical parameters so as to understand the influence of cooking in digestion behavior as well as the effect of food matrix. Key References: • 1A. K. Shrestha and L. Dabit (2012). Starch digestibility of rice and its potential link to current diabetes

epidemic in South Asian populations. Accepted as Invited Speaker in 46th Annual Australian Institute of Food Science and Technology Convention, Brisbane, 16th July, 2013.

• R. Eyaru, A. K. Shrestha and J. Arcot (2009). Effect of various processing techniques on digestibility of starch in red kidney bean (Phaseoulus vulgaris) and two varieties of peas (Pisum sativum). Food Research International, 42, 956-962.

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Title of Project: Getting Your Hands Dirty – Soil Biology & Genomics Contact: Brajesh Singh Email: [email protected] Telephone: 4570 1329

Contact: Jeff Powell Email: [email protected] Telephone: 4570 1093 Campus project is offered and conducted: Hawkesbury (Hawkesbury Institute for the Environment)

Background:

Soil Biology & Genomics is one of three themes within the recently established Hawkesbury Institute for the Environment. Select one of our ready-made projects from the list found at http://www.uws.edu.au/hie/scholarships/hie_honours_scholarships or develop your own with any one of the eight active researchers in this field. The Hawkesbury Institute has the facilities, the people, and the enthusiasm to make honours projects challenging and rewarding for capable science undergraduates.

Aim of the Study:

Have you thought about:

- soil invertebrate communities under climate change? - estimating the contributions of mycorrhizal fungi to forest tree productivity? - invasive species and the link between the aboveground and belowground systems?

The research team is focusing on how environmental change influences the amazing diversity of life in soils, including its fungi, bacteria and animals. It seeks to link above- and below-ground research by understanding how changes in soil biodiversity may impact soil processes that are important for plant and ecosystem health. They utilise a range of technologies in their research and aim to generate research outcomes that enable us to build a holistic picture of how soil organisms influence the ecology, growth and diversity of plants and animals. The outcomes from the research will be used to improve future strategies for ecosystem management, increased plant production, carbon sequestration, and remediation of contaminated soils. Contact one of our theme leaders (above) or any researcher within this theme – contacts can be found directly on the theme’s website at http://www.uws.edu.au/hie/research/soil_biology_and_genomics.

Methods:

The methods employed will depend on your project and what will most benefit you as a budding researcher. The Hawkesbury Institute has extensive field facilities, laboratories, glasshouses and equipment available including the recently established EucFACE field site. View some of our facilities at http://www.uws.edu.au/hie/facilities.

Ethics Application requirements:

Most projects will not require ethics clearance, but check this with your proposed supervisor.

Key References:

See below or refer to our extensive list of publications at http://www.uws.edu.au/hie/publications.

Nazaries L, Pan Y, Bodrossy L, Baggs EM, Millard P, Murrell JC, Singh BK, (2013) 'Evidence of Microbial Regulation of Biogeochemical Cycles from a Study on Methane Flux and Land Use Change', Applied and Environmental Microbiology, vol.79, no.13, pp 4031-4040

Drigo B, Kowalchuk GA, Knapp BA, Pijl AS, Boschker HTS, van Veen JA, (2013) 'Impacts of 3 years of elevated atmospheric CO2 on rhizosphere carbon flow and microbial community dynamics', Global Change Biology, vol.19, no.2, pp 621-636 Anderson IC, Drigo B, Keniry K, Ghannoum O, Chambers SM, Tissue DT, Cairney JW, (2013) 'Interactive effects of preindustrial, current and future atmospheric CO2 concentrations and temperature on soil fungi associated with two Eucalyptus species', FEMS Microbiology Ecology, vol.83, no.2, pp 425-437

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Title of Project: What does it mean to ‘understand’ a chemistry concept? Supervisor: Prof Roy Tasker Email: [email protected] Co-supervisor: To be decided Email: Campus/s project is offered and conducted: This project will use the new R&D multimedia visualisation laboratory in K16 at the Hawkesbury Campus. Background (200 words): As soon as you think you really understand a concept in chemistry, with further study you inevitably find out there is more to it. So if you are teaching chemistry, at what point do you stop delving into more and more detail? How do you ‘scaffold’ and ‘chunk’ ideas so students can build their own mental models? What teaching strategies are most effective for showing the interconnections between concepts in science?

For example, what exactly is a molecule? What does this representation communicate correctly, and incorrectly, about this molecule?

Aim of Study: Through discussion, we will identify a topic in chemistry for you to study in detail. After a comprehensive literature search on the common misconceptions on this topic, we will develop a short teaching sequence of learning activities based on a learning model generated from cognitive science. This sequence will be tested on a limited group of students, and any learning gains analysed in terms of learning style, motivation, and other variables. The project offers the opportunity to delve into your choice of a chemistry topic in detail, explore its facets in terms of accepted mental models, and confront the challenge of helping others to develop their own deep understanding. This project is designed for students who anticipate teaching chemistry as a career at secondary or tertiary level. Methods: The methods you will use to probe student understanding will differ, according to the topic. They may involve one-to-one interviews, and/or use of computer-delivered learning activities. Ethics Application Requirements: This research would require submission of documentation for approval by the Human Research Ethics Committee to conduct experiments with students.

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Key References: 1. Tasker, R., & Dalton, R. (2006). Research into Practice: Visualisation of the Molecular World Using Animations.

Chemistry Education Research and Practice, 7(2), 141 - 159. See http://www.rsc.org/images/Tasker-Dalton%20paper%20final_tcm18-52113.pdf .

2. Tasker, R., & Dalton, R. (2008). Visualising the Molecular World: The Design, Evaluation, and Use of Animations. In Gilbert, J.K., Reiner, M., Nakhleh, M. (Eds.) Visualisation: Theory and Practice in Science Education. Series: Models and Modelling in Science Education Vol. 3, Chapter 6, pp103 - 132. ISBN 978-1-4020-5266-8 Springer. http://www.springer.com/west/home/education?SGWID=4-40406-22-173670362-detailsPage=ppmmedia%7Ctoc

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Title of Project: Evaluation of the Effectiveness of Odyssey as a Learning Tool Supervisor: Prof Roy Tasker Email: [email protected] Co-supervisor: To be decided Email: Campus/s project is offered and conducted: This project will use the new R&D multimedia visualisation laboratory in K16 at the Hawkesbury Campus. Background (200 words): The heart of the software tool Odyssey is a molecular dynamics force-field engine that can simulate the molecular- level behaviour of substances and solutions with unrivalled accuracy. A student can build a simulation of a substance or mixture, manipulate variables like temperature, and plot graphs of kinetic energy distribution and other quantities to answer “What if …?” types of questions. We can also produce graphical models ( e.g., electrostatic potential maps on electron density isosurfaces) in the research-level modelling program Spartan, and manipulate these in Odyssey. Together with VisChem animations, we now have excellent tools for visualising the molecular world and putting the power of computational chemistry in the hands of students, even at first-year level. Aim of Study: This project is designed for students who anticipate teaching chemistry as a career at secondary or tertiary level. We know that student misconceptions in chemistry often stem from an inability to visualise structures and processes at the molecular level. We also know that we cannot change a student’s mental model of this level just by showing them a different one, no matter how compelling the tools are. The aim of this project will be evaluate the effectiveness of Odyssey activities with Essential Chemistry 1 or Essential Chemistry 2 students in 2014. This project would involve reading the literature on student misconceptions, interviewing students, analysing and interpreting data from surveys and computer-tracked interactions. Methods: The methods you will use to probe student understanding will differ, according to the topic. They may involve one-to-one interviews, and/or use of computer-delivered learning activities. You would learn to use molecular simulation software programs such as Odyssey and Spartan to produce learning resources, then develop and evaluate learning designs that use them.

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Ethics Application Requirements: This research would require submission of documentation for approval by the Human Research Ethics Committee to conduct experiments with students. Key References:

3. Tasker, R., & Dalton, R. (2006). Research into Practice: Visualisation of the Molecular World Using Animations. Chemistry Education Research and Practice, 7(2), 141 - 159. See http://www.rsc.org/images/Tasker-Dalton%20paper%20final_tcm18-52113.pdf .

4. Tasker, R., & Dalton, R. (2008). Visualising the Molecular World: The Design, Evaluation, and Use of Animations. In Gilbert, J.K., Reiner, M., Nakhleh, M. (Eds.) Visualisation: Theory and Practice in Science Education. Series: Models and Modelling in Science Education Vol. 3, Chapter 6, pp103 - 132. ISBN 978-1-4020-5266-8 Springer. http://www.springer.com/west/home/education?SGWID=4-40406-22-173670362-detailsPage=ppmmedia%7Ctoc

158

Title of Project: Evaluation of Visualisation Resources Using Eye Tracking Supervisor: Prof Roy Tasker Email: [email protected] Co-supervisor: To be decided Email: Campus/s project is offered and conducted: This project will use the new R&D multimedia visualisation laboratory in K16 at the Hawkesbury Campus. Background (200 words): In collaboration with colleagues in the US working in a large NSF-funded research project entitled Design

Principles for Effective Molecular Animations (see http://artsci.drake.edu/honts/molviz/ ) we found

distinct differences between novice and expert perception of events portrayed in VisChem animations.

For instance, in a complex animation portraying simultaneous events (see figure below), 61% novices and

35% experts attended only to Event 2, whilst 11% novices and 29% experts attended only to Event 1.

These data were obtained from stimulated-recall interviews that rely on interviewees recalling their initial

perceptions accurately, and from analysis of answers to pre/post-questions.

In a preliminary demonstration with eye-tracking hardware/software we were able to record both the

area and duration of eye fixation as a student viewed the animation. These data are an objective

measurement of attention to different parts of an animation, and provide an invaluable complement, and

supplement, to the subjective, qualitative data obtained in interviews. Together, eye tracking and student

interview protocol analysis enable us to correlate attention to specific key features (from eye tracking

data), with engagement with the animation (from interview data and pre/post-test data), and to evaluate

new animations and new attention-focussing strategies faster and more accurately.

Figure 1. The movie frame above depicts two events occurring simultaneously – electron cloud gained by

a silver ion (upper right), and electron cloud lost by a copper atom (lower left). Our results from interviews indicate novices and experts perceive these events differently, but this demonstration of eye-

tracking data provides compelling, direct evidence.

Event 1 (reduction of silver ion, grey)

Event 2 (oxidation of copper atom, yellow)

Red dots indicate position and duration (dot size) of eye fixation by tracking eye movement

159

Aim of Study: This project would involve reading the literature on student misconceptions in a specific topic, and cognitive processing of visual information; conducting eye-tracking experiments; interviewing students; and analysing and interpreting interview data and eye-tracking recordings. The primary aim of the project is to determine what a student learns from a visualisation, with information on what they attend to in the visualisation. Then the challenge is to develop a learning design that addresses the issues identified, and to evaluate the learning design with students. The project would suit someone interested in how we learn from visualisation resources as a foundation for science teaching at secondary or tertiary level. Methods: The main methods involve analysing data obtained from

• student answers before and after a computer-delivered visualisation • video and audio recording of pairs of students whilst they think aloud as they use a visualisation • one-to-one interviews with students before and after they have used a visualisation • eye-tracking experiments

Ethics Application Requirements: This research would require submission of documentation for approval by the Human Research Ethics Committee to conduct experiments with students. Key References:

5. Tasker, R., & Dalton, R. (2006). Research into Practice: Visualisation of the Molecular World Using Animations. Chemistry Education Research and Practice, 7(2), 141 - 159. See http://www.rsc.org/images/Tasker-Dalton%20paper%20final_tcm18-52113.pdf .

6. Jean-Michel Boucheix, Richard K. Lowe, Dian K. Putri, Jonathan Groff (2013) Cueing animations: Dynamic signaling aids information extraction and comprehension Learning and Instruction, Volume 25, June 2013, Pages 71-84

160

Title of Project: Circling the Globe – Ecosystem Function & Integration Contact: Mark Tjoelker Email: [email protected] Telephone: 4570 1618

Contact: Sally Power Email: [email protected] Telephone: 4570 1359

Campus project is offered and conducted: Hawkesbury (Hawkesbury Institute for the Environment) Background:

Ecosystem Function & Integration is one of three themes within the recently established Hawkesbury Institute for the Environment. Select one of our ready-made projects from the list found at http://www.uws.edu.au/hie/scholarships/hie_honours_scholarships or develop your own with any one of the ten active researchers in this field. The Hawkesbury Institute has the facilities, the people, and the enthusiasm to make honours projects challenging and rewarding for capable science undergraduates.

Aim of the Study:

Have you thought about:

- remote sensing of burn severity and post-fire recovery in eucalypt forests? - water-use and biodiversity in bio-remediation? - biophysical principles underlying fuel moisture dynamics?

The research team is focusing on the dynamics of ecosystem function in response to global environmental change. They explore how changes in climate, land use and cover affect the exchanges of carbon, nutrients, water, and energy. Using models, they integrate processes at scales ranging from leaf to globe. The research addresses key questions such as how will Australia’s native plant species and ecosystems respond to climate warming, rising atmospheric concentrations of CO2, and altered rainfall patterns? What are the consequences of biodiversity loss for carbon, water and nutrient cycling? To answer these and other pressing questions, the team use observations, experiments and integrative modelling. Contact one of our theme leaders (above) or any researcher within this theme – contacts can be found directly on the theme’s website at http://www.uws.edu.au/hie/research/ecosystem_function_and_integration.

Methods:

The methods employed will depend on your project and what will most benefit you as a budding researcher. The Hawkesbury Institute has extensive field facilities, laboratories, glasshouses and equipment available including the recently established EucFACE field site. View some of our facilities at http://www.uws.edu.au/hie/facilities.

Ethics Application requirements:

Most projects will not require ethics clearance, but check this with your proposed supervisor.

Key References:

See below or refer to our extensive list of publications at http://www.uws.edu.au/hie/publications.

Bowman DMJS, Murphy BP, Boer MM, Bradstock RA, Cary GJ, Cochrane MA, Fensham, Krawchuk MA, Price OF, Williams RJ, (2013) 'Forest fire management, climate change and the risk of catastrophic carbon losses', Frontiers in Ecology and Environment, vol.11, no.2, pp 66-67

Fry EL, Manning P, Allen DGP, Hurst A, Everwand G, Rimmler M, Power SA, (2013) 'Plant Functional Group Composition Modifies the Effects of Precipitation Change on Grassland Ecosystem Function', PLoS ONE, vol.8, no.2, Article no.e57027

Héroult A, Lin Y-S, Bourne A, Medlyn BE, Ellsworth DS, (2013) 'Optimal stomatal conductance in relation to photosynthesis in climatically contrasting Eucalyptus species under drought', Plant, Cell and Environment, vol.36, no.2, pp 262-274

161

Title of Project: Cloning and characterisation of putative aluminium transporter in Saccharomyces cerevisiae Supervisor: Dr Ming Wu Email: [email protected] Co-supervisor: Dr Zhonghua Chen Email: [email protected] Campus/s project is offered and conducted: Campbelltown and Hawkesbury Background (200 words): Metal ion homeostasis is fundamental to cell function. The tight control of metal ion uptake in the cell is elaborately regulated via gene expression and signal transduction. The key frontline molecule in this process is the transporters in plasma membrane. In the past studies, we have tried to understand aluminium toxicity using the model organism, Saccharomyces cerevisiae. The complete set of deletion mutants (5047) was screened using a range of concentrations of aluminium sulfate (0.4 mM, 0.8 mM, 1.6 mM and 3.2 mM). Two standing-out genes are found to be involved in Al transport. Their deletion leads to the Al resistance phenotype. This project is to clone the two genes and further investigate their role in Al transportation. Aim of Study: To clone the putative Al transporters and further investigate their role in Al transportation Methods: Cytotoxicity assays, Molecular cloing and expression, confocal microscope, ICP-MS and PCR Ethics Application Requirements: No required Key References: Can be requested by email.

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Honours projects offered at

Parramatta Campus

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Title of Project: New methods to characterise breakfast cereals Supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Dr Ashok Shrestha Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

Breakfast cereals are nutrient dense processed foods and expected to have several health benefits. They are expected to have a low glycemic index (low GI, which means that they are digested slowly) [1]). Most of them are also externally fortified with folic acid (Pteroylglutamic acid) to prevent the incidence of neural tube defects [2]. Their analysis is complicated by the fact that they are only partially soluble in water [3]. Traditional methods of folic acid analysis such as HPLC, or microbiological assay are tedious and time consuming. Our preliminary results showed that capillary electrophoresis is a fast method to detect folic acid. It is also an excellent tool of the separation and detection of sugars [4]. Aim of Study:

The aim of the project is to develop new methods for a faster, more accurate, and robust characterisation of cereal-based foods, based on free-solution capillary electrophoresis. Folates and sugars will be quantified. These methods could be compared to the established, but tedious and expensive, HPLC methods. The full samples will also be characterised with solid-state NMR spectroscopy, thus avoiding dissolution artefacts. Methods:

Capillary electrophoresis, NMR spectroscopy, high-performance liquid chromatography (HPLC). Ethics Application Requirements:

Not applicable Key References: [1] AC Dona, G Pages, RG Gilbert, M Gaborieau, PW Kuchel, Kinetics of in vitro digestion of starches

monitored by time-resolved 1H nuclear magnetic resonance. Biomacromolecules, 2009, 10, 638-644 [2] J Arcot, A Shrestha, Folate: methods of analysis. Trends in Food Science & Technology, 2005, 16, 253–

266 [3] S Schmitz, AC Dona, P Castignolles, RG Gilbert, M Gaborieau, Assessment of the extent of starch

dissolution in dimethylsulfoxide by 1H NMR spectroscopy. Macromolecular Bioscience 2009, 9, 506-514

[4] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A, 2013, 1291, 179-186

164

Title of Project: Characterization of pH-responsive polymers to better understand controlled polymerization Supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Dr Franck d’Agosto Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

pH-responsive polymers see their solubility in water greatly affected by pH. They are commonly used to stabilize colloids. The team of Prof Bernadette Charleux and Dr Franck d’Agosto (University Lyon 1, France) developed a technology to control the polymerization of a variety of monomers in emulsion [1]. This process relies on the use on stable radical, nitroxides. The visit to UWS of Emilie Groison, PhD student enrolled in Lyon, France showed the potential of the capillary electrophoresis method we develop in our group to separate the pH-responsive stabilizer. Aim of Study:

The aim of the project is investigate the potential of capillary electrophoresis [2] to separate these complex samples. The samples are synthesized in Lyon. The project consists in separating them and characterizing them to finally explore the mechanism of the nitroxide-mediated polymerization process. Methods:

Capillary electrophoresis. Ethics Application Requirements:

not applicable Key References: [1] E Groison, S Brusseau, F D’Agosto, S Magnet, R Inoubli, L Couvreur, B Charleux, Well-defined

amphiphilic block copolymer nanoobjects via nitroxide-mediated emulsion polymerization. ACS Macro Letters, 2012, 1, 47-51

[2] M Gaborieau, TJ Causon, Y Guillaneuf, EF Hilder, P Castignolles, Molecular weight and tacticity of oligoacrylates by capillary electrophoresis-mass spectrometry. Australian Journal of Chemistry 2010, 63, 1219-26

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Title of Project: Photo-oxidation of sugars and polysaccharides for their characterization by capillary electrophoresis Supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Dr Christopher Fellows Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

Carbohydrates make up most of the living world around us. Their identification and quantification is generally sought after in many fields such as food and beverage analysis, plant analysis, fermentation studies and metabolism studies. Current analysis methods are not adapted to the complexity of the polysaccharides and derived carbohydrates mixtures. We have shown that free-solution capillary electrophoresis offers the possibility of simple and robust separations for monosaccharides (such as from plant fibers) [1] or polysaccharides (such as gellan gums [2] and chitosan [3]). The method has a high potential: the sensitivity of the detection is however relatively low for most important polysaccharides such as starch, glucomannans, galactomannans or chitosan.

Monosaccharides detection is possible, and highly sensitive through a photo-oxidation process taking place directly in the capillary window. The aim of this project is to apply this photo-oxidation to key polysaccharides chitosan, starch, glucomannans and galactomannans (comparing also to polyol models such as poly(vinyl alcohol)). The influence of the addition of photo-oxidant, such as a radical photo-initiator,[4] will be studied, exploring the possibilities of breakthrough in terms of detection sensitivity. Aim of Study:

The aim of the project is to better understand the photo-oxydation of sugars and to improve the detection of sugars and polysaccharides with capillary electrophoresis. Methods:

Capillary electrophoresis, Photochemistry. Ethics Application Requirements:

Not applicable Key References: [1] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of

monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A, 2013, 1291, 179-186

[2] DL Taylor, CJ Ferris, AR Maniego, P Castignolles, M in het Panhuis, M Gaborieau, Characterization of gellan gum by capillary electrophoresis. Australian Journal of Chemistry, 2012, 55, 1156-1164

[3] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378

[3] P Castignolles, AN Nikitin, L Couvreur, G Mouraret, B Charleux, J-P Vairon, Pulsed laser polymerization of alkyl acrylates: Potential effects of the oxygen presence and high laser power. Macromolecular Chemistry and Physics 2006, 207, 81-89

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Title of Project: Smart polymers as the additives of the future Supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Prof Mathias Destarac Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

Smart’ polymeric materials react to changes in temperature or pH. These ‘smart’ polymers are intensively researched for use in drug delivery, water purification and more. The ‘smart’ behaviour of these materials is making their characterization difficult by common liquid chromatography methods. The team of Prof Mathias Destarac (University Paul Sabatier, Toulouse, France) developed a new technology to synthesize some complex polymers where part of the polymer chain is cationic, while the other part is neutral and thermoresponsive [1]. The cationic part ensures this polymer has great adhesive properties on a number of substrates. The thermoresponsive properties mean that the materials is water-soluble at low temperature but not at high temperature. Aim of Study:

The characterization of these polymers failed up to now due to the presence of the charges. We propose to use this charge at our advantage and separate the polymers using and electric field, i.e. using capillary electrophoresis [2]. The self-assembly of these polymers lead to powerful and fascinating structures that could be characterized using solid-state NMR [3]. Methods:

Capillary electrophoresis, solid-state NMR spectroscopy. Ethics Application Requirements:

Not applicable Key References: [1] M Destarac, On the critical role of RAFT agent design in reversible addition-fragmentation chain

transfer (RAFT) polymerization. Polymer Reviews 2011, 51, 163-187 [2] M Gaborieau, TJ Causon, Y Guillaneuf, EF Hilder, P Castignolles, Molecular weight and tacticity of

oligoacrylates by capillary electrophoresis-mass spectrometry. Australian Journal of Chemistry 2010, 63, 1219-26

[3] W Gu, M Gaborieau, VT Huynh, PL de Souza, MH Stenzel, Functionalization of microspheres with malonates using Michael addition as a pathway to create a drug delivery system for platinum drugs for the treatment of liver cancer. Polymer 2011, 52, 5993-6002

167

Title of Project: Marsupial Pouch Lipids: a source of antibiotics? Supervisor: Jo-Anne Chuck Email: [email protected] Co-supervisor: Julie Old Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words): The pouch of the mother is a hostile environment for marsupial young as they are born relatively underdeveloped compared to most mammals. The immune system of these young is also underdeveloped yet they have to survive in an external environment. In the pouch, they are exposed to transient micro-organism as well as those colonising the pouch and others originating from faecal material. It is hypothesized that the lining of the pouch supports the young by secretion of antimicrobial compounds until its immune system develops and/or animal leaves the pouch. Though some analysis has been done on water soluble components of pouch secretions, little work has been done on lipophillic secretions. Exploring the diversity of antimicrobial compounds in the pouch is significant both for our understanding of the development of marsupials but also for drug discovery. Aim of Study: The aim of the study is to bioprospect for antimicrobial compounds from lipid extracts obtained from the pouches of marsupials. These samples have already been collected however no wide screening of the samples has been undertaken. Methods: The project will be microbiological and chemical based. The project will use fluorescent stains to assess the viability of micro-organisms when exposed to lipid extracts. This will involve fluorescent microscopy and microbiology techniques. Some analytical chemistry may also be involved for instance LC-MS, GC-MS and liponomic technology. Ethics Application Requirements: N/A Key References: Old JM, Deane EM. (2000)Development of the immune system and immunological protection in marsupial pouch young. Dev Comp Immunol. Jul;24(5):445-54.

168

Title of Project: Characterizing polysaccharides for a better health Supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Prof. Kelvin Chan Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

Polysaccharides are a major and key component of our diet (starch is typically 50 % of our calories). Glucomannan is a polysaccharide obtained from Konjac and popular to prepare for example jellies in different Asian countries.[1] Glucommannans have health benefits, as fibers, against for example type II diabetes and obesity. However, the reasons for these benefits are not known at the molecular level. It is thus necessary to characterize glucomannans at the molecular level. Galactomannnans are used as viscosifier in the food industry and other fields. They have similarities in chemical composition to the glucomannans: their characterisation is more advanced but tedious, time-consuming and still plagued by a number of uncertainties.[2]

Complex polysaccharides’ structure and their molecular motion can be understood through the characterisation by solid-state NMR [3]. Solid state NMR will be applied to the glucomannans and galactomannans: this characterization is possible without any modification of the sample (no dissolution or any type of modification is necessary). We also have recently showed that (free-solution) capillary electrophoresis can separate polysaccharides according to their composition [4-5]: the method is new, easy, fast and is applied for the first time to glucomannans and galactomannans. Aim of Study:

The aim of the project is to characterize ‘real’ glucomannans and galactomannans samples developing new capillary electrophoresis and NMR spectroscopy methods for applications as healthier food. Methods:Solid-state NMR spectroscopy, Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] M Chua, K Chan, TJ Hocking, PA Williams, CJ Perry, TC Baldwin, Methodologies for the extraction and

analysis of konjac glucomannan from corms of Amorphophallus konjac K. Koch. Carbohydrate Polymers, 2012, 87, 2202-2210

[2] MA Pollard, R Kelly, PA Fischer, EJ Windhab, B Eder, R Amado, Investigation of molecular weight distribution of LBG galactomannan for flours prepared from individual seeds, mixtures, and commercial samples. Food Hydrocolloids 2008, 22, 1596-1606

[3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386

[4] DL Taylor, CJ Ferris, AR Maniego, P Castignolles, M in het Panhuis, M Gaborieau, Characterization of gellan gum by capillary electrophoresis. Australian Journal of Chemistry, 2012, 55, 1156-1164

[5] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378

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Title of Project: Towards high quality bioplastics Supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Aurelia Charlot Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

It is desirable to replace materials derived from oil, such as current plastics, by new ones derived from renewable resources such as cellulose or galactomannans. Cellulose is a significant waste from agriculture, while galactomannans like guar gums are an additive used in the food industry whose resources are largely under-used [1,2]. This is due to the poor intrinsic mechanical properties of these polysaccharides as well as their high sensitivity to moisture. These polysaccharides are often chemically modified to adjust performance to the level of current plastics.

Polysaccharides consist of molecules with different types of saccharide units (glucose, galactose, mannose), different molecular weights and different topologies: linear chains or branched ones. The chemical modification improves the properties but also add to the complexity of the molecules. The elucidation of their structure is needed for the scientific design of bioplastics. Aim of Study:

Potential bioplastics derived from cellulose or galactomannans will be characterized and assessed. With solid-state NMR [3] we elucidate the interplay between molecular structure and molecular motions, and explore the crucial role of moisture. We use capillary electrophoresis (in the critical conditions) [4-5] to separate compounds with different compositions and different degrees of modification. We collaborate with Dr Aurelia Charlot and Prof Etienne Fleury (INSA, Lyon, France) to answer these fundamental questions. This project has a strong potential to lead to industrial collaborations. Methods:

Capillary electrophoresis, Solid-state NMR spectroscopy. Ethics Application Requirements:

Not applicable Key References: [1] C Lacroix, E Sultan, E Fleury, A Charlot, Functional galactomannan platform from convenient

esterification in imidazolium-based ionic liquids. Polymer Chemistry 2012, 3, 538-46 [2] G Mangiante, P Alcouffe, B Burdin, M Gaborieau, E Zeno, M Petit-Conil, J Bernard, A Charlot, E Fleury,

Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization. Biomacromolecules 2013, 14, 254-63

[3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386

[4] DL Taylor, CJ Ferris, AR Maniego, P Castignolles, M in het Panhuis, M Gaborieau, Characterization of gellan gum by capillary electrophoresis. Australian Journal of Chemistry, in press, 2012, 55, 1156-1164

[5] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378

170

Title of Project: Effect of temperature on chain length of amylose in rice starch Supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Rachelle Ward Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

The amount of amylose and the nature of its branching are influenced by night temperatures [1]. This degree of branching has been shown to directly impact the cooking quality and texture of the rice grain. The Waxy gene has been linked to changes in amylose although this does not explain all observed changes in amylose. One hypothesis to explain the amylose structure is the changed activity of starch branching enzymes, however these environmental influences, in combination with genetic differences in the waxy and starch branching enzyme genes have not been studied in the Australian rice germplasm.

This investigation will analyse 12 parental lines of rice (Oryza sativa) from the rice breeding program at the Yanco Agricultural Institute. These lines comprise of three variations of interest in the waxy gene, high amylose and low amylose contents (identifiable by 3 SNPs within the Waxy gene) along with two possible combinations of Starch Branching Enzymes. The 12 plants will be grown in replicates of 12 in a glasshouse until flowering where half will be moved to a higher temperature glasshouse and the other half to a control/normal temperature. Upon harvesting the amylose from the grain will be measured, then extracted by use of hot water and the chain-lengths and frequency measured by capillary electrophoresis and NMR. Aim of Study:

The aim of the project is measure degrees of branching using NMR spectroscopy [2] and amylose chain lengths using capillary electrophoresis to identify the effect of night time temperatures on the activity starch branching enzyme. Methods:

Capillary electrophoresis, NMR spectroscopy. Ethics Application Requirements:

not applicable Key References: [1] PA Counce, RJ Bryant, CJ Bergman, RC Bautista, YJ Wang, TJ Siebenmorgen, KAK Molenhauer, JFC

Meullenet, Rice Milling Quality, Grain Dimensions, and Starch Branching as Affected by High Night Temperatures. AACC International, 2005, 82(6), 645-648

[2] M Gaborieau, H DeBruyn, S Mange, P Castignolles, A Brockmeyer, RG Gilbert, Synthesis and characterization of synthetic polymer colloids colloidally stabilized by cationized starch oligomers. Journal of Polymer Science Part A Polymer Chemistry, 2009, 47, 1836-1852

171

Title of Project: Smart polymers for anticancer drug delivery Supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Prof. Janice Aldrich-Wright Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

Smart polymers such as hyperbranched poly(acrylic acid) and chitosan are being tested for drug delivery. Our colleagues in Marseilles, France, can control the synthesis to obtain a range of branched poly(acrylic acid). These polyacrylates are also ‘smart’ polymeric materials; they react to changes in pH, as well as chitosan. Our preliminary results show that polyacrylates are branched [1,2]. They also show that capillary electrophoresis can separate them according to their branching structure [3], while it separates chitosan by its composition[4]. Aim of Study:

The aim is to assess different synthetic pathways to bind anticancer drugs such as cisplatin to the novel polyacrylates synthesized in Marseilles, as well as to chitosan. Methods:

Capillary electrophoresis. (In)organic synthesis. Ethics Application Requirements:

not applicable Key References: [1] Gaborieau, P Castignolles, Size-exclusion chromatography (SEC) of branched polymers and

polysaccharides. Analytical and Bioanalytical Chemistry 2011, 399, 1413-1423 [2] P Castignolles, R Graf, M Parkinson, M Wilhelm, M Gaborieau, Detection and quantification of

branching in polyacrylates by size-exclusion chromatography (SEC) and melt-state 13C NMR spectroscopy. Polymer 2009, 50, 2373-2383.

[3] AR Maniego, D Ang, Y Guillaneuf, C Lefay, D Gigmes, JR Aldrich-Wright, M Gaborieau, P Castignolles, Separation of poly(acrylic acid) salts according to the topology using capillary electrophoresis in the critical conditions. Analytical and Bioanalytical Chemistry, 2013, in press

[4] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378

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Title of Project: Polysaccharide-water interactions by solid-state NMR Supervisor: Dr Marion Gaborieau Email: [email protected] Co-supervisor: Dr Patrice Castignolles Email: [email protected] Co-supervisor: Dr Robert Graf Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words):

Starch is the main source of energy in human diet, as it is a major component of wheat, maize, potatoes and rice. It is renewable, cheap and biodegradable, and therefore has major applications in the paper, pharmaceutical and textile industries. Starch is a chemically simple polymer (a homopolymer of glucose) but it has a very complex macromolecular (branched) and supramolecular structure, with six identified hierarchical levels, on scales ranging from nm to mm. Its hydrogen-bonding capacity, provided by three hydroxyl groups per glucose unit, is crucial for its solid-state structure as well as its behavior in solution. Starch granules contain water molecules, which are an integral part of the semi-crystalline structure. Starch-water interactions play an important role in the mechanical properties of starch-based bioplastics. They also define the first stages of cooking of starch, and therefore are expected to play a role in diet-related diseases such as obesity and diabetes.

Solid-state Nuclear Magnetic Resonance (NMR) is an invaluable tool in the study of polymer materials such as polysaccharides: it yields local information on their structure and dynamics [1,2]. Aim of Study:

In this study, the local dynamics of starch and residual water will be investigated on the molecular level as a function of sample temperature by solid-state nuclear magnetic resonance (NMR) methods. The study will also be extended to other polysaccharides. This will shed light onto hydrogen bonding capacity of starch (as a model polysaccharide) and its interactions with water. It will help elucidate the poorly-understood endothermic transition observed by differential scanning calorimetry for many polysaccharides [3]. This project will build on the expertise of Dr Marion Gaborieau in solid-state nuclear magnetic resonance (NMR) of native and functionalized polysaccharides. Methods:

Solid-state NMR spectroscopy, differential scanning calorimetry (DSC). Ethics Application Requirements:

not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and

dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386

[2] G Mangiante, P Alcouffe, B Burdin, M Gaborieau, E Zeno, M Petit-Conil, J Bernard, A Charlot, E Fleury, Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization. Biomacromolecules 2013, 14, 254-263

[3] IAM Appelqvist, D Cooke, MJ Gidley, SJ Lane, Thermal properties of polysaccharides at low moisture: An endothermic melting process and water-carbohydrate interactions. Carbohydrate Polymers 1993, 20, 291-299

173

Title of Project: Anion Detection by Temperature Control Using Smart Materials Supervisor: Dr Feng Li Email: [email protected] Co-supervisor: Prof. Jean-François Letard (CNRS, France) Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words): The ubiquity of anions such as halides, phosphates and carboxylates in nature, which play essential roles in chemistry, biology, medicine and the environment as catalysts, drugs, food additives, agricultural fertilizers and industrial materials, has led to considerable attention to address their sensing, separation and transport by the scientific community. In addition, most of the important biomolecular targets such as peptides, nucleotides, phospholipids, and carbohydrates are anionic species in aqueous solution. Hence, there is a significant need for the development of new classes of anion receptors that operate with high selectivity and sensitivity in water, in order to better characterise anion association patterns based on novel binding features. Although the majority of anion receptors have been based around organic scaffolds, there has been an accelerating recent trend towards the use of metal-based anion host species. However, to date most anion receptors can only sense and/or select one or two anions using spectroscopic techniques. Therefore, the development of sensors based on new materials for the detection of a large range of anionic species in aqueous solution by straightforward techniques remains a significant challenge. Aim of Study: This project aims to explore anion-sensing based on spin-crossover scaffolds by temperature control. The incorporation of spin-switching sites into supramolecular capsules will see the development of unique self-indicating molecular receptors, in turn spurring the development of new classes of anion indicators and chemosensors. Outcomes on both the fundamental and applied levels will pave the way toward molecular devices for anion sensing and transport. Methods: To employ directed assembly procedures, stepwise syntheses and template controls for constructing innovative nanometre-scale materials.

Ethics Application Requirements:

N/A Key References: J. L. Sessler, P. A. Gale and W.-S. Cho, Anion Receptor Chemistry, RSC publishing, Cambridge, UK, 2006. P. A. Gale, Chem. Commun., 2011, 47, 82-86. Z. Ni, M. P. Shores, J. Am. Chem. Soc. 2009, 131, 32-33. F. Li, R. Delgado and V. Félix, Eur. J. Inorg. Chem., 2005, 4550-4561.

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Title of Project: Molecular Recognition Using Macrocyclic Compounds Supervisor: Dr Feng Li Email: [email protected] Co-supervisor: Prof. Janice Aldrich-Wright Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words): Molecular recognition has been a vigorous, fast-growing and fascinating area of research interest in coordination and supramolecular chemistry, and biological processes. Macrocyclic compounds are of great interest as receptors for the molecular recognition of cations, anions and neutral molecules, since their cavity size, shape, and components can be readily varied. Therefore, the design and synthesis of novel functional macrocyclic receptors is crucial and a challenge for researchers. Aim of Study: This research project is concentrated on polyoxa-polyaza macrocyclic compounds and new functional cryptands containing different spacers as receptors for selectively binding metal ions, anions and neutral species. The strength of the association of these guests is evaluated by the determination of the binding constant by spectroscopic or potentiometric techniques. For the successful receptors, they can be selected in the detection or quantification of “real-life” samples using straightforward analytical techniques.

Methods: To employ high dilution and metal template controls for constructing macrocyclic compounds.

Ethics Application Requirements:

N/A Key References: F. Li, R. Delgado, A. Coelho, M. G. B. Drew, and V. Félix, Tetrahedron, 2006, 62, 8550-8558. N. Bernier, S. Carvalho, F. Li, R. Delgado and V. Félix, J. Org. Chem., 2009, 4819-4827 F. Li, S. Carvalho, R. Delgado, M. G. B. Drew, and V. Félix, Dalton Trans., 2010, 9579-9581.

175

Title of Project: Discrete Interlocked/Intertwined Supramolecular Assemblies Supervisor: Dr Feng Li Email: [email protected] Co-supervisor: Prof. Len Lindoy (USyd) Email: [email protected] Campus/s project is offered and conducted:Parramatta Background (200 words): In the realm of supramolecular chemistry, finite nano-scale interlocked/intertwined metallo-supramolecular ensembles with interesting and beautiful molecular structures have received very considerable attention over recent years. Such metallo-architectures range from large metal protein to a small number of intricately interwoven structures that bridge the boundaries between Art and Science. These ensembles, which typically form on the nanometer scale, display both considerable beauty and applications. However, the generation of new structures of this type has remained a very significant synthetic challenge. A condition for the rational strategies of such metal organic structures is that the metal ion(s) and organic component(s) display the required steric and electronic complementarity to promote formation of the molecular architecture of interest. Aim of Study: The application of cation and/or anion templated syntheses to the design and construction of new practical molecular devices and machines, including sensors, (opto)electronic devices (including electronic components ranging from transistors to logic gates) and enzyme-like catalysts remains a significant intellectual and practical challenge. To probe the construction of novel molecular devices, which show molecular movement of interlocked/intertwined constituent parts that can be triggered by cation and/or anion binding controls, is anticipated to lead to novel supramolecular assemblies for practical applications in molecular memory and molecular machines. The proposed interlocked supramolecular systems could also contribute to the development of nanoscale molecular machines that, for example, might mimic the role of sophisticated biomolecular entities. Methods: The application of cation and/or anion templated syntheses to the design and construction of new practical molecular devices and machines

Ethics Application Requirements:

N/A Key References: L. F. Lindoy, & I. M. Atkinson, Self-Assembly in Supramolecular Systems (Royal Society of Chemistry, 2000). J.- P. Sauvage, & C. Dietrich-Buchecker, eds Molecular Catenanes, Rotaxanes and Knots (Wiley-VCH, 1999). F. Li, J. K. Clegg, R. B. Macquart, G. V. Meehan and L. F. Lindoy, Nature Commun., 2011, 2: 205.

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Title of Project: Metal Directed Assembly of Discrete Supramolecular Systems Supervisor: Dr Feng Li Email: [email protected] Co-supervisor: Prof. Jean-François Letard (CNRS, France) Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words): The metal-ion directed assembly of discrete molecular architectures, and especially those with interesting supramolecular topologies, has received very considerable attention over recent years, because of their specific applications in recognition, catalysis, magnetic materials and synthetic membranes for ion channels. Yet the rational design and synthesis of discrete coordination architectures or polymeric coordinations still remains a great challenge. The ultimate aim of metallo-supramolecular systems is to control the structure of the target product with expected properties and functions. These include novel redoxactive, magnetism, photoactive, conductive (including superconductive), catalytic and non-linear optical properties.

Aim of Study: The design of suitable organic ligands and the selection of the correct metal ions for favoring structure-specific self-assembly play important roles in the construction of discrete coordination architectures. Thus much attention in this project will be focused on the synthetic approach and the structural control of coordination architectures, especially for those with multidimensional structures. The organic components to be employed all incorporate 𝛽-diketonate, pyridylpyrazole and/or imidazole schiff base sites - motivated in part by the availability of the extremely well documented metal coordination behaviour of these ‘classical’ coordination entities. Furthermore, characterization and functionality of such systems will be investigated for specific applications in host-guest chemistry and spin-crossover (SCO) studies. This will elucidate fundamental aspects of metallo-supramolecular chemistry (including the role that both metal ions and organic species may play in the assembly process), factors influencing host-guest inclusion behaviour and the nature of electronic/magnetic interactions between spin-crossover and magnetic coupling energies.

Methods: To employ directed assembly procedures, stepwise syntheses and template controls for constructing innovative nanometre-scale materials.

Ethics Application Requirements:

N/A Key References: J. K. Clegg, F. Li, K. A. Jolliffe, G. V. Meehan and L. F. Lindoy, Chem. Commun., 2011, 6042-6044. F. Li, J. K. Clegg, R. B. Macquart, G. V. Meehan and L. F. Lindoy, Nature Commun., 2011, 2: 205. F. Li, J. K. Clegg, L. Goux-Capes, G. Chastanet, D. M. D'Alessandro, J.-F. Létard, and C. J. Kepert, Angew. Chem. Int. Ed., 2011, 50, 2820-2823. F. Li, J. K. Clegg, D. Price, and C. J. Kepert, Inorg. Chem., 2011, 50, 726-728.

177

Title of Project: Effect Crystallite and Particle Sizes on the Electrochemical Performance of a Novel LiMnPO4 Battery Cathode Material Supervisor: Dr. Adriyan Milev Email: [email protected] Co-supervisor: A/Prof. Kamali Kannangara Email: [email protected] Co-supervisor: Dr. Laurel George Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words): The rechargeable lithium-ion battery, introduced by Sony Corporation in 1991, now plays a major role in consumers' everyday life. It is considered as the key technology which has the potential to undergo further development to be used in hybrid or all-electric cars. However, success in these important areas will require further improvement in the capability of the technology for extended service life at higher charge and discharge rates, together with better retention of performance under repetitive charge–discharge (‘cycling’) duty(1). After a number of cathode materials were found unsuitable for use in large lithium-ion electric vehicle batteries, lithium transition-metal phosphate (LiMPO4, M= Fe, Mn, Co) is now regarded as the best candidate (2, 3). The advantages for LiMPO4 when compared to the existing electrodes such as LiCoO2,

LiMnO2 include: improved safety through higher resistance to thermal runaway, longer cycle-life, low cost of raw materials, low toxicity, and high thermal stability at fully charged state(4). So far (years 2012-2013), only one member of this class, LiFePO4, has been employed in advanced batteries. The research is now focused on the more challenging LiMnPO4 material, which offers higher theoretical energy density (~700 Wh/kg) compared to LiFePO4 (~580 Wh/kg). However the synthesis of LiMnPO4 material is challenging and further optimisations are required before it can be considered commercially viable. Aim of Study: The principal aim of this project is to investigate the electrochemical properties of LiMnPO4 cathode material using a proprietary technology developed at UWS. The specific aims are to investigate:

1. Electrochemical performance changes with the decrease of the crystallite sizes from macro-crystalline to nanocrystalline.

2. Electrochemical performance changes with the increase of the cathode surface area from several m2/g to several hundred m2/g.

Methods: Macrocrystalline LiMnPO4 material will be provided. The Honours student will convert the macrocrystalline material to a series of nanocrystalline samples with progressively decreasing crystallite samples using the existing facilities in the nanotechnology laboratory. The crystallinity changes will be investigated by X-ray diffraction analysis, whereas the surface areas will be measured using BET facility. Selected samples will be characterised by Scanning electron microscopy. The characterised materials will be used to prepare a series of battery cathodes which will be assembled in real button-size batteries. The electrochemical performance of the assembled batteries will investigated by; (i) cyclic voltammetry, (ii) chrono-potentiometry (charge/discharge cycling) and (iii) electrochemical impedance spectroscopy. Ethics Application Requirements: N/A Note: Because of the commercial sensitivity of the project the successful Hons applicant will be required to sign a UWS Deed of Assignment. The Deed of Assignment creates important legal obligations in relation to ownership of intellectual property and also includes a non disclosure agreement.

178

Key References: 1. Armand M, Tarascon JM. Building better batteries. Nature. 2008;451:652-7. 2. Recham N. Ionothermal synthesis of tailor-made LiFePO4 powders for Li-ion battery applications. Chem Mater. 2009;21:1096-107. 3. Zaghib K, Mauger A, Gendron F, Julien CM. Relationship between local structure and electrochemical performance of LiFePO4 in Li-ion batteries. Ionics. 2008;14(4):271-8.. 4. Padhi AK, Nanjundaswamy KS, Goodenough JB. Phospho-olivines as positive electrode materials for rechargeable lithium batteries. J Electrochem Soc. 1997;144:1188-94.

179

Title of Project: Investigation of the surface properties of complex lipid films Supervisor: Thomas Millar Email: [email protected] Co-supervisor: Burkhardt Schuett Email: [email protected] Campus/s project is offered and conducted: Parramatta Background (200 words): The tear film of the eye is covered by a thin lipid layer which is essential for the proper spreading and stabilization of the tear film. Without it, people develop dry eye. This project is part of ongoing work in determining the structure and function of this film. Based on this research, eye drops are being developed in conjunction with a commercial partner. Aim of Study: To examine the effects of different lipids and proteins on the surface pressure and viscoelastic properties of meibomian lipid films. Methods: Lipid films will be spread on a liquid subphase and their dynamic surface pressure will be measured using a Langmuir trough. Ethics Application Requirements: None Key References: 1. Schuett, B.S. & Millar, T. J. (2012) Lipid component contributions to the surface activity of meibomian lipids. Invest Ophthal Vis Sci 53:7208-7219. 2. Millar, T.J. (2013) A mechanism to explain the behaviour of spread films of meibomian lipids. Curr Eye Res 38:220-223. 3. Palaniappan, C.K., Schuett, B.S., Bräuer, L, Schicht, M & Millar TJ. (2013) Effects of keratin and lung surfactant proteins on the surface activity of meibomian lipids. Invest Ophthal Vis Sci 54:2571-2581. 4. Raju, S.R., Palaniappan, C.K., Ketelson, H.A., Davis, J.W. & Millar TJ. (2013) Interfacial dilatational viscoelasticity of human meibomian lipid films. Curr Eye Res. 38:817-824 5. Schuett, B.S. & Millar, T.J. (2013) An investigation of the likely role of (O-acyl) Ω-hydroxy fatty acids in meibomian lipid films using (O-oleyl) Ω -hydroxy palmitic acid as a model. Exp. Eye Res. 115:57-64.

180

Title of Project: High Density Titanium Dioxide for Solar Applications Supervisor: Dr Leigh Sheppard Email: [email protected] Co-supervisor: Dr Marta Bello Lamo Email: [email protected] Co-supervisor: Dr Richard Wuhrer Email: [email protected] Campus/s project is offered and conducted: Hawkesbury and Parramatta Background (200 words): Titanium dioxide, TiO2, has emerged as an important material for the efficient harvesting of solar energy for alternative fuel generation (hydrogen) and water decontamination. This is due to its photosensitivity, outstanding corrosion resistance, and low cost. However, TiO2 also exhibits a broad range of functional properties of which not all are favourable for solar energy conversion. The Solar Energy Technologies research group seeks to understand how the properties of TiO2 can be tailored for best practical performance through the appropriate control of fundamental processing parameters. Aim of Study: This project is aimed at establishing a processing route that yields highly dense TiO2 from loose TiO2 powder. This will be achieved by investigating the influence of controlled processing variables, such as temperature, gas phase composition and time, on the microstructure of TiO2 powder compacts. Methods: Students undertaking this project will learn about the development of advanced ceramics and their engineering for solar applications. Students will also gain experience and skills with the use of advanced instrumentation for materials characterisation, particularly scanning electron microscopy and x-ray diffraction, in addition to the tools associated with the forming and fabrication of oxide-based semiconductors. Ethics Application Requirements: Nil Key References: L. Sheppard and J. Nowotny, “Materials for Photoelectrochemical Energy Conversion”, Advances in Applied Ceramics, 106 (2007) 9-20

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Title of Project: Novel Semiconducting Thin Films for Solar Applications Supervisor: Dr Leigh Sheppard Email: [email protected] Co-supervisor: Dr Marta Bello Lamo Email: [email protected] Co-supervisor: Dr Richard Wuhrer Email: [email protected] Campus/s project is offered and conducted: Hawkesbury and Parramatta Background (200 words): Titanium dioxide, TiO2, has emerged as an important material for the efficient harvesting of solar energy for alternative fuel (hydrogen) generation and water decontamination. This is due to its photosensitivity, outstanding corrosion resistance, and low cost. However, TiO2 also exhibits a broad range of functional properties, of which not all are favourable for energy conversion. The Solar Energy Technologies research group seeks to understand how the properties of TiO2 can be tailored for best practical performance through the appropriate control of processing parameters. Aim of Study: This project is aimed at establishing a deposition protocol for the preparation of doped TiO2 thin films that exhibit high sensitivity to sunlight. Using reactive magnetron sputtering, an advanced technique for the deposition of thin film semiconductors, Ti, O2 and various light-sensitive elements will be combined to form a novel TiO2-based compounds that is sensitive to the visible portion of the solar spectrum. Methods: Students undertaking this project will learn about the fabrication of advanced thin film materials using reactive magnetron sputtering. They will also gain experience with the use of advanced instrumentation for materials characterisation, including scanning electron microscopy and x-ray diffraction. Ethics Application Requirements: Nil Key References: L. Sheppard and J. Nowotny, “Materials for Photoelectrochemical Energy Conversion”, Advances in Applied Ceramics, 106 (2007) 9-20

182

Title of the project: Starch digestibility and glycemic behavior of major South Asian diets Supervisor: Ashok K Shrestha, PhD Email: [email protected] Co-supervisor: TBA Campus project is offered and conducted: Hawkesbury or Parramatta campus Background: Diabetes, Type 2, previously regarded as a disease of affluent has now threatened the health and economies of all nations. There are now close to 300 million diabetes in the world, Asia host 60% of them. India alone reported to have 61 million diabetic people and predicted to reach 100 million diabetic by 2030. This disproportionate rise in diabetes in South Asia has been blamed to the sedentary life-style, poor diet (ingredient) choice and obesity. The traditional diets eaten in Indian subcontinent are mostly carbohydrate based as meat, fish and eggs are sparingly eaten due to affordability, religious reasons or simply due to dietary habits. Recent economic revolution in India showed urban populations eat less of the traditional foods and lots of calories come from fats, animal foods, refined foods and high volume of sweets. Rice and wheat based foods are staple diet followed by tubers, legumes etc. In vitro digestibility study showed rice varieties are highly digestible1. Even among the Indian population, the perception of their traditional foods is not encouraging, such as, ‘Asian people are getting a lot of diseases, like diabetes, because of what we’re eating. The doctors have said ‘‘it’s what you are eating that is causing you to have so many diseases’. Glycemic index (GI) and glycemic loads (GL) are two major indicators of how much sugars are loaded in the body, after ingesting foods. Most of the processed foods, breakfast cereals in particular are heavily loaded with sugars and are rapidly absorbed in the body. Aim of the Study: The aim of this project is to study the digestibility and glycemic behaviour as well as physicochemical properties of commonly eaten (staple) South Asian diets that influence the rate of glucose release. The outcome of the study will link to potential impact on the glycemic health of the people in South Asian region. Methods: This study will perform digestibility studies on both the raw and cooked foods and characterize the physicochemical parameters so as to understand the influence of cooking in digestion behavior as well as the effect of food matrix. Key References: • 1A. K. Shrestha and L. Dabit (2012). Starch digestibility of rice and its potential link to current diabetes

epidemic in South Asian populations. Accepted as Invited Speaker in 46th Annual Australian Institute of Food Science and Technology Convention, Brisbane, 16th July, 2013.

• R. Eyaru, A. K. Shrestha and J. Arcot (2009). Effect of various processing techniques on digestibility of starch in red kidney bean (Phaseoulus vulgaris) and two varieties of peas (Pisum sativum). Food Research International, 42, 956-962.

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Honours projects offered at

Penrith Campus

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Title of Project: The adaptation to the mainstream in elite sport: An Australian Aboriginal perspective Supervisor: Andrew Bennie Email: [email protected] Co-supervisor: TBC Email: Campus/s project is offered and conducted: Penrith Campus Background (200 words): Sport plays an important and powerful role for many Australians. For indigenous communities, sport can be a way of integrating to the larger society and provides opportunities for social participation, social identity construction and meaningful engagement in the workforce (Campbell & Sonn, 2009). Besides Campbell & Sonn’s recent study of Indigenous AFL players’ perspectives on transitioning into the AFL, little is known about the nature of Indigenous athlete development and the issues and challenges associated with transition and relocation to the mainstream societal context. As such, further research is warranted into other male and female sport contexts to help develop a more detailed understanding of the challenges that young Indigenous athletes face. Aim of Study: This project aims is to investigate the struggles and adaptation strategies of these elite Aboriginal athletes as they progress in their sporting careers in sports such as rugby league, football (soccer), cricket, netball and basketball. Methods: This project will be based on the Cultural Sport Psychology (CSP) framework which aims to better understand respondents’ perspectives from Indigenous cultures through qualitative interviews. Interviews allow for detailed and personalised responses where the participants provide deep explanations of their experiences over time. The constant comparative method (Côté, Salmela, Baria, & Russell, 1993) will be used to generate key themes from the interviews. This project may be suitable for 2-3 honours students to cover a wider range of sports. Ethics Application Requirements: An ethics application will be required. Key References: Campbell, E. E. & Sonn, C. C. (2009). Tranisitioning into the AFL: Indigenous football players’ perspectives.

Athletic Insight, 11(3). Côté, J., Salmela, J. H., Baria, A., & Russell, S. J. (1993). Organizing and interpreting unstructured

qualitative data. The Sport Psychologist, 7(2), 127-137. Schinke, R. J., Michel, G., Gauthier, A. P., Pickard, P., Danielson, R., Peltier, D., et al. (2006). The adaptation

to the mainstream in elite sport: A Canadian Aboriginal perspective. The Sport Psychologist, 20, 435-448.

185

Title of Project: Pathways to Paralympic Sport: Athlete and Coach Development Supervisor: Andrew Bennie Email: [email protected] Co-supervisor: TBC Email: Campus/s project is offered and conducted: Penrith; this topic has the potential for 2-3 students. Background (200 words): While there is an abundance of research surrounding the coaching of able-bodied athletes, limited research focuses on the Paralympic movement. Some of the research completed within a sample of sports for people with disabilities, focuses on the roles, philosophies, and strategies for athlete development, coach behaviours and their influence on athlete motivation as well as athlete leaders perceptions of team cohesion (Banack, Sabiston & Bloom, 2011; Tawse, Bloom, Sabiston & Reid, 2012). Many of these studies have been completed with a Canadian sample across varying summer and winter sports and there is potential to build a body of knowledge about pathways to elite coaching and participation for Australian athletes and coaches within the Paralympic sport movement. Aim of Study: This study has two aims:

1. Investigate career evolution and knowledge development for coaches of Paralympic athletes 2. Explore the pathway from youth sport to Paralympic competition amongst athletes with a

physical disability

Methods: This project will be based on interviews with current Paralympic Coaches and athletes. Ethics Application Requirements: An ethics application will be required. Key References: Banack, H. R., Sabiston, C.M., & Bloom, G. A. (2011). Coach Autonomy Support, Basic Need Satisfaction,

and Intrinsic Motivation of Paralympic Athletes. Research Quarterly for Exercise and Sport, 82(4), 722-730.

Patton, M. Q. (2002). Qualitative research and evaluation methods (3rd ed.). Thousand Oaks: Sage Publications.

Tawse, H., Bloom, G. A., Sabiston, C. M., & Reid, G. (2012). The role of coaches of wheelchair rugby in the development of athletes with a spinal cord injury. Qualitative Research in Sport, Exercise and Health, 4(2), 206-225.

186

Title of Project: Physical Activity in Physical Education: How do Teaching Styles influence Physical Activity in Western Sydney Secondary Schools? Supervisor: Andrew Bennie Email: [email protected] Co-supervisor: TBC Email: Campus/s project is offered and conducted: Penrith; this topic has the potential for 2-3 students. Background (200 words): In the western Sydney area, there are a significantly higher proportion of people aged 16 or over who are overweight or obese and who do not have adequate physical activity levels (NSW Health, n.d.). This is of significant concern because young people who are overweight or obese are more likely to develop gastrointestinal, endocrine and cardiovascular problems as well as greatly increased likelihood of becoming obese adults (NSW Health, n.d.). While, there is an abundance of literature about student MVPA levels in PE and young people’s views about the barriers and enablers for being physically active (see Allender, Cowburn, & Foster, 2006; Fairclough & Stratton, 2005; Rees et al., 2006), little is known about PE teachers perceptions of PA and how they prepare and implement lessons for increasing MVPA. School teachers are crucial to students’ initial experiences in PA during structured and unstructured play and clearly more needs to be done by researchers, teachers and parents to combat the high rates of obesity amongst young people in western Sydney.

Aim of Study: The purpose of this research is to investigate the nature of, and attitudes towards, physical activity (PA) in physical education (PE) within western Sydney secondary schools. Through qualitative interviews, this study will inquire about current New South Wales (NSW) teachers' approaches toward teaching PE, the value they place on PA in PE lessons, as well as they the teaching strategies they use to influence PA in their PE lessons. The data from this project will be used to prepare additional research into the impact that different teaching styles have on student’s moderate to vigorous physical activity (MVPA) levels during PE lessons. Methods: This project will be based on interviews with current PDHPE teachers in NSW Government, Catholic, Independent schools. Interviews enable a rich description and interpretation of the participants’ feelings, thoughts, emotions and beliefs about their experiences in a particular context. Ethics Application Requirements: Ethic application has been completed. Key References: Allender, S., Cowburn, G., & Foster, C. (2006). Understanding participation in sport and physical activity

among children and adults: A review of qualitative studies. Health Education Research, 21(6), 826-835.

Fairclough, S., & Stratton, G. (2005). Physical activity levels in middle and high school physical education: A review. Pediatric Exercise Science, 17, 217-236.

Patton, M. Q. (2002). Qualitative research and evaluation methods (3rd ed.). Thousand Oaks: Sage Publications.

187

Title of Project: Investigating physical activity and health (several topics available) NOTE: Projects are available for one or more Honours students Supervisor: Emma George Email: [email protected] Co-supervisor: Gregory Kolt Email: [email protected] Co-supervisor: Dr Thomas Astell-Burt Email: [email protected] Campus/s project is offered and conducted: Campbelltown or Penrith Background (200 words): The 45 and Up Study (www.45andup.org.au) is the largest ongoing study of healthy ageing in the Southern Hemisphere. Data on a range of health, quality of life, and demographic factors (including physical activity levels and time spent sedentary) has been collected from 267,153 men and women aged 45 years and over, living in NSW. Of particular interest to our research team are some of the health and well-being issues that relate to Greater Western Sydney - a culturally diverse and rapidly growing region in NSW. We are also interested in Culturally and Linguistically Diverse (CALD) groups in relation to health promoting behaviours. The Greater Western Sydney region encompasses areas of both socioeconomic advantage and disadvantage, and the population experiences high rates of overweight and obesity and is overrepresented in a range of adverse health conditions. Findings from this study will help inform the design of future health promotion initiatives and policies relevant to areas such as Greater Western Sydney with its culturally diverse population. Aim of Study: More than one Honours student can work in this area, and topics can be shaped to the expertise and interest of the students. Utilising existing baseline data from the large-scale 45 and Up Study, the aim of these projects is to examine the cross-sectional associations between physical activity and/or sedentary time and a range of health-related variables in middle-aged and older Australians. These topics could focus on issues specific to Greater Western Sydney or on topics relevant to particular population groups (e.g., CALD groups). Students with an interest in the role physical activity plays in health and an interest in epidemiology will have the opportunity to select health outcomes of interest for examination. The findings from these projects will contribute to a growing body of evidence related to the health and wellbeing of Australian adults. Methods: Students will carry out an extensive literature review in the area of their project, will use existing data from The 45 and Up Study to conduct cross-sectional analyses, and will work towards publication of their findings in a suitable journal. Students will join a strong research team and will gain good support in research training. Opportunities will exist for suitable students to progress into a PhD after completion of their Honours degree. Ethics Application Requirements: Only reciprocal ethics approval (at UWS) will be required for this project, as approval has already been obtained for the larger Study and related sub-studies. Key References: 45 and Up Study Collaborators. (2008). Cohort profile: The 45 and Up Study. International Journal of Epidemiology, 35(5), 941-947. George, E. S., Rosenkranz, R. R., & Kolt, G. S. (2013). Chronic disease and sitting time in middle-aged Australian males: findings from the 45 and Up Study. International Journal of Behavioral Nutrition and Physical Activity, 10, 20. doi: 10.1186/1479-5868-10-20.

188

Title of Project: A Cluster Randomised Controlled Trial of a School-based Physical Activity Intervention in At-risk Communities: The Adolescent Motivation in Physical EDucation (AMPED) Program Supervisor: Chris Lonsdale Email: [email protected] Co-supervisor: Morwenna Kirwan, Email: [email protected] Co-supervisor: Emma George Email: [email protected] Campus/s project is offered and conducted: Campbelltown or Penrith Background (200 words): This project is a large randomised trial of a school-based intervention that is designed to promote physical activity in adolescents. Students who are interested in physical activity promotion and/or the effects of physical activity on a variety of outcomes (e.g., mental health, academic performance) will have the opportunity to discuss their ideas with the research team and decide on a specific topic to investigate during their honours year. Aim of Study: To be determined based on student interest. Methods: To be determined based on student interest. Possible sources of data that will be collected in the larger project include:

6. Physical activity measured via accelerometer data. 7. Questionnaires. 8. Interviews. 9. Video observation of physical education lessons. 10. Support website usage by teachers involved in the intervention.

Ethics Application Requirements: None, ethical approval already obtained. Key References: Aelterman, N., et al. (2013). Development and evaluation of a training on need-supportive teaching in physical education: Qualitative and quantitative findings. Teaching and Teacher Education, 29, 64-75. Lonsdale, C., et al. (2013). A systematic review and meta-analysis of interventions designed to increase moderate-to-vigorous physical activity in school physical education lessons. Preventive Medicine, 152-161.

189

Honours projects offered externally

190

Title of Project: Developing New Radio-metal PET Tracers: Ligands for Oxophillic Radio-metals Supervisor: Janice Aldrich-Wright Email: [email protected] Co-supervisor: Ivan Greguric Email: [email protected] Co-supervisor: Nigel Lengkeek Email: [email protected] Co-supervisor: Ben Fraser Email: [email protected] Campus/s project is offered and conducted: ANSTO Background (200 words): Zirconium-89 (89Zr) is a positron emitting radionuclide well suited to Positron Emission Tomography (PET) molecular imaging studies. Its long physical half-life, 78.4 hrs, makes it uniquely suited to imaging with molecules that have long biological half-lives and localisation times, the key example being monoclonal antibodies, so called 89Zr-Immuno-PET. Indeed, there are numerous 89Zr-labelled antibodies either in development or undergoing clinical trials in the US and Europe. There has been tremendous growth in the area of ‘biologicals’ for treatment of human disease, particularly cancer. Radiolabelled versions of the ‘biologicals’ can be used to determine a patients response to a particular treatment, an important step on the road to truly personalised medicine. The bacterial iron siderophore, desferrioxamine B (DFO), a trishydroxamate ligand is the most promising ligand for 89Zr and it is easily incorporated onto biomolecules. An pictorial representation is shown below. Radiolabelling of DFO-functionalised antibodies with 89Zr is rapid and efficient with the radiolabelled biomolecules being largely stable in-vivo. However, there are a growing number of cases that show significant bone uptake. This is undesirable as it can lead to radiation to the sensitive bone marrow. To combat this problem we are developing a series of tetrahydroxamate ligands (an example is shown below) to tie up the two remaining coordination sites of Zr where other ligands can displace the DFO. This will hopefully improve their in-vivo stability. The ligands will be suitable for a range of emerging PET radioisotopes including 45Ti (t1/2 = 3.08 hr), 44Sc (t1/2 = 3.93 hr), 90Nb (t1/2 = 14.6 hr) and 89Zr (t1/2 = 78.4 hr).

N CH3

O

OHNH

O

N

O

OHNH

55

2

O

N

O

OHH2N

5

2

N N NO

NHO

ONOH

O

HNR

ONOH

O

NOH

Desferrioxamine B (DFO)

New Tetrahydroxamate Ligand Systems

n

nn

n

191

Student top-up scholarships - AINSE UNSW students undertaking honours projects in collaboration with ANSTO are eligible to apply for an honours scholarship ($5000 stipend) from The Australian Institute of Nuclear Scientists and Engineers (AINSE). Visit the website below for more information. http://www.ainse.edu.au/grad_students2/honours_scholarships Aim of Study: To synthesise and characterise tetrahydroxamate ligands for Zr89 complexation and antibody radiolabelling. Methods: Uses inorganic and synthetic chemistry for preparation of new ligands and ‘cold’ metal complexes; radiochemistry for the optimisation of radiolabelling procedures and biological labelling; , Prep-HPLC, radio-HPLC, radio-TLC, NMR, UV-Vis, ESI-MS, LC-MS-MS, pH auto-titrations and CD for characterisation; molecular modelling for design of ligands and biophysical techniques for the assessment of radiolabelled biological molecules. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required Key References: 1. Bergeron, R.J., Synthesis and Solution Structure of Microbial Siderophores. Chem. Rev., 1984. 84: p.

587 - 602. 2. Butler, A. and R.M. Theisen, Iron(III)-siderophore coordination chemistry: Reactivity of marine

siderophores. Coord. Chem. Rev., 2010. 254: p. 288 - 296. 3. Hider, R.C. and X. Kong, Chemistry and Biology of Siderophores. Nat. Prod. Rep., 2010. 27: p. 637 -

657. 4. Raymond, K.N., G. Muller, and B.F. Matzanke, Complexation of Iron by Siderophores: A review of

their solution and structural chemistry and biological function. Top. Curr. Chem., 1984. 123: p. 50 - 101.

5. Deri, M.A., et al., PET imaging with 89Zr: From radiochemistry to the clinic. Nuclear Medicine and Biology, 2013. 40(1): p. 3-14.

6. Zalutsky, M.R., Potential of Immuno–Positron Emission Tomography for Tumor Imaging and Immunotherapy Planning. Clinical Cancer Research, 2006. 12(7): p. 1958-1960.

7. Vugts, D.J. and G.A.M.S. van Dongen, 89Zr-labeled compounds for PET imaging guided personalized therapy. Drug Discovery Today: Technologies, 2011. 8(2–4): p. e53-e61.

8. Wright, B.D. and S.E. Lapi, Designing the Magic Bullet? The Advancement of Immuno-PET into Clinical Use. Journal of Nuclear Medicine, 2013. 54(8): p. 1171-1174.

192

Title of Project: Development of diagnostic radiopharmaceuticals Supervisor: Janice Aldrich-Wright Email: [email protected] Co-supervisor: Ivan Greguric Email: [email protected] Co-supervisor: Ben Fraser Email: [email protected] Campus/s project is offered and conducted: ANSTO and Campbelltown Background (200 words):

Radiopharmaceuticals are made up of two components; a radioisotope (eg. fluorine-18, technetium-99m, zirconium-89) attached to a biological vector (small molecule, protein, antibody etc). The biological vector facilitates transport and uptake of the radioisotope in the body. Depending upon the type of radioisotope chosen, radiopharmaceuticals can be used for diagnosis or therapy. [18F]fluorodeoxyglucose or FDG – the world’s most commonly prescribed fluorine-18 radiopharmaceutical – is used to diagnose many forms of cancer through positron emission tomography (PET) imaging (see LHS image). FDG is preferentially taken up in cancerous cells and is used for cancer diagnosis and for monitoring treatment progression. http://upload.wikimedia.org/wikipedia/commons Developing New Fluorine-18 radiopharmaceuticals Although numerous radioisotopes are available for Positron Emission Tomography (PET) imaging, fluorine-18 remains very popular due to favourable physical properties. These include low energy positron emission (0.202 MeV), excellent decay profile (97% β+ emission),

advantageous half-life (110 mins) allowing multi-step chemical syntheses and similar steric and electronic properties to the hydroxyl group. Currently we are developing fluorine-18 radiopharmaceuticals as diagnostic imaging agents for Alzheimer’s disease (metal chelators) and depression (organic cation 3 transporter inhibitors). Our honours projects typically have 2-4 stages depending upon the rate of research progression; Stage 1 - Organic synthesis. A small compound library is synthesised and fully characterised based upon an established lead compound. Stage 2 - In vitro screening. The library of compounds are screened in biological assays to measure their potential for further development into PET imaging agents. Stage 3 – Radiolabelling. Selected compounds are radiolabelled using newly developed or established radiolabelling methodologies. Stage 4 – In vivo screening. Promising compounds from in vitro screening studies and radiolabelling studies are evaluated in animal models of disease. Aim of Study: To synthesise and characterise [18F]diagnostics PET imaging agents for Alzheimers’s disease or depression. Methods: Uses molecular modelling for design, radiochemistry and synthetic chemistry, preparative HPLC, radioHPLC, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS).

193

Ethics Application Requirements: None required Key References: 1. C. P. Ferri, M. Prince, C. Brayne, H. Brodaty, L. Fratiglioni, M. Ganguli, K. Hall, K. Hasegawa, H.

Hendrie, Y. Huang, A. Jorm, C. Mathers, P. R. Menezes, E. Rimmer and M. Scazufca, Lancet, 2005, 366, 2112-2117.

2. L. Cai, S. Lu and V. W. Pike, Eur. J. Org. Chem., 2008, 2008, 2853-2873. 3. S. M. Ametamey, M. Honer and P. A. Schubiger, Chem. Rev., 2008, 108, 1501-1516. 4. P. W. Miller, N. J. Long, R. Vilar and A. D. Gee, Angew. Chem. Int. Ed., 2008, 47, 8998-9033. 5. A. Bush and R. Tanzi, Neurotherapeutics, 2008, 5, 421-432. 6. A. I. Bush, J. Alzheimers Dis., 2008, 15, 223-240. 7. N. Vasdev, P. Cao, E. M. van Oosten, A. A. Wilson, S. Houle, G. Hao, X. Sun, N. Slavine, M. Alhasan,

P. P. Antich, F. J. Bonte and P. Kulkarni, MedChemComm, 2012. 8. R. E. Horton, D. M. Apple, W. O. Owens, N. L. Baganz, S. Cano, N. C. Mitchell, M. Vitela, G. G.

Gould, W. Koek and L. Daws Student top-up scholarships - AINSE UNSW students undertaking honours projects in collaboration with ANSTO are eligible to apply for an honours scholarship ($5000 stipend) from The Australian Institute of Nuclear Scientists and Engineers (AINSE). Visit the website below for more information. http://www.ainse.edu.au/grad_students2/honours_scholarships

194

Title of Project: Transcriptional interference within prostate cancer intergenic linked loci Supervisor: Assoc/Professor Raymond Clarke Email: [email protected] Campus/s project is offered and conducted: Ingham Institute Liverpool Background (200 words): Prostate Cancer is the most common cancer in Australian men. A large percentage of prostate cancer is familial in origin. Most of the 74 loci linked to familial prostate cancer occur in intergenic regions of the genome and little is known regarding their functional association with prostate cancer. Novel methodology from our laboratory has identified previously unknown transcriptional interactions in intergenic regions of the genome. This project will involve evaluation of prostate cancer linked loci in search of evidence of transcriptional interactions to help explain the function of these intergenic linked loci in prostate cancer. Aim of Study: Identify transcription interactions within Prostate cancer intergenic linked loci Methods: Cell culture, electrophoresis, rtPCR and QPCR Ethics Application Requirements: No Key References: Student will need to be computer literate with a passion for human genetics and demonstrated experience and ability with PCR.

195

Title of Project: Multi-morbidity in Aboriginal Patients at Orange Aboriginal Medical Service Supervisor: A/Prof Wendy Stevens Email: [email protected] Campus/s project is offered and conducted: Bathurst Rural Clinical School Background (200 words): Multi-morbidity refers to the co-existence of two or more diseases in the same person. Multi-morbidity varies with age and ethnicity and impacts on quality of life, utilisation of medical services, hospitalisation, treatment and mortality. Prevalence, age of onset and patterns of multi-morbidity may differ between Aboriginal and non-Indigenous Australians. Currently little is known about multi-morbidity in Aboriginal people in Australia and how this compares with the non-Indigenous population. Such knowledge can inform treatment approaches and health service planning. Aim of Study:

1) To document the prevalence and patterns of multi-morbidity in the Aboriginal population of Orange Aboriginal Medical Service (OAMS).

2) To compare multi-morbidity in this Aboriginal population with reported multi-morbidity in the Australian population as a whole.

Methods: A retrospective audit of clinical records of all active Aboriginal patients at OAMS (ie all Aboriginal people who have attended OAMS over the past 2 years) will be conducted. Demographic information (including age, gender and post code), number and types of diseases, and age of onset of the disease will be documented. Diseases will be counted and classified according to various commonly used multi-morbidity measures such as the Cumulative Illness Rating Scale. Multi-morbidity in the study population will then be compared with reported multi-morbidity in the Australian population. Ethics Application Requirements: Once a student has selected the topic, Bathurst Rural Clinical School (BRCS) will submit an application to the Aboriginal Health and Medical Research Council (AH&MRC). Once ethical approval has been obtained from the AH&MRC, BRCS will submit an application for reciprocal approval to UWS HREC. Key References: • Barnett K, Mercer S, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and

implications for health care, research, and medical education: a cross-sectional study. Lancet Online Publication May 2012; DOI:10.1016/S0140-6736(12)60240-2

• Starfield B, Kinder K. Multimorbidity and its measurement. Health Policy 2011;103:3-8. • Boyd CM, Fortin M. Future of Multimorbidity Research: How Should Understanding of Multimorbidity

Inform Health System Design? Public Health Reviews. 2010;32:451-74. • Britt H, Harrison C, Miller G and Knox S. Prevalence and patterns of multimorbidity in Australia. MJA

2008; 189: 72–77. • Jain S. Morbidity and multi-morbidity in Australia: Evidence from the National Health Surveys. J Aust

Pop Assoc 1993;10(1):31-52.

196

Title of Project: Health Needs Assessment of the Orange Aboriginal Medical Service Community Supervisor: A/Prof Wendy Stevens Email: [email protected] Campus/s project is offered and conducted: Bathurst Rural Clinical School Background (200 words): Significant and persisting health inequalities exist between Aboriginal and non-Aboriginal people in NSW. These inequalities occur across a range of key health indicators including risk factors, access to health services, maternal and child health, chronic disease and life expectancy. Orange Aboriginal Medical Service (OAMS) is a Community Controlled Organization that provides primary health care plus some specific programs to Orange and surrounding communities. It has a client list of over 3,200 Aboriginal people. In order to better address the health inequalities in their local community, OAMS initiated a population health program in December 2012. This program includes the ongoing identification of major health issues within the OAMS community, current service provision and any gaps in this service provision. Ongoing service improvement is based on these findings. Aim of Study:

i) To document the prevalence of risk factors (such as smoking and obesity) and a particular disease (such as cardiovascular disease) in the OAMS patient population

ii) To document what services OAMS provides for addressing these risk factors and disease and to identify gaps in service provision.

Methods: A literature review will be performed to identify comparative data in NSW and elsewhere. OAMS patient data will be extracted from Communicare (patient management software) to identify the prevalence of the particular risk factors and disease in the OAMS patient population. These data will then be compared with data from NSW and elsewhere. Interviews or focus groups will be conducted with OAMS staff and clients to identify current service provision and service gaps. The findings will be presented to OAMS so as to inform service improvement initiatives. Ethics Application Requirements: Once a student has selected the topic, Bathurst Rural Clinical School (BRCS) will submit an application to the Aboriginal Health and Medical Research Council (AH&MRC). Once ethical approval has been obtained from the AH&MRC, BRCS will submit an application for reciprocal approval to UWS HREC. Key References: • Centre for Epidemiology and Evidence. The health of Aboriginal people of NSW: Report of the Chief

Health Officer, 2012. Sydney: NSW Ministry of Health. 2012. • Department of Health and Ageing. National Aboriginal and Torres Strait Islander Health Plan 2013-

2023. Australian Government, Canberra, 2013. • Western NSW Local Health Diostrict and Western NSW Medicare Local. Western NSW Health Needs

Assessment 2013. Dubbo: WNSW LHD & ML; 2013.


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