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RESEARCH HONOURS 2018 DIVISION OF MEDICINE This booklet contains a list of available research projects for 2018
RESEARCH HONOURS 2018 DIVISION OF MEDICINE
This booklet contains a list of available research projects for 2018
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Contents Course Objectives ....................................................................................5
Academic requirements ..............................................................................6
Scholarships............................................................................................6
Your application to do honours .....................................................................6
Student Expectations .................................................................................7
Course Coordinator ...................................................................................7
Additional Contacts ...................................................................................7
Clinical and Population Health based Projects (involving Human Subjects and/or Data) ..8
Automated control of inspired oxygen therapy in neonates ...............................8
Overcoming the physiological effects of apnoea in preterm infants .....................9
Patient-centred health care: Investigating the views of stakeholder groups ........ 10
Heterologous effect of diphtheria, tetanus, acellular pertussis vaccination on influenza vaccine challenge in the elderly ................................................. 11
How is chronic kidney disease identified and managed in general practice? ......... 13
How can influenza vaccination of pregnant women be optimally delivered in general practice? ........................................................................................ 14
How do GPs implement treatment guidelines in patients with a pre-existing condition? ....................................................................................... 15
Using advanced imaging to gain a better understanding of hand osteoarthritis ..... 16
Translational Health Services Research .................................................... 16
Unnecessary variation in hospital length of stay: are we causing more suffering and how do we prevent it?......................................................................... 17
ASPREE. A double-blind randomised controlled trial of low dose aspirin for primary prevention in the aged ........................................................................ 17
ASPREE Healthy Ageing Biobank ............................................................. 18
A randomised clinical trial of STAtin therapy for Reducing Events in the Elderly (STAREE) ........................................................................................ 18
Acute pancreatitis admissions in Hobart ................................................... 18
Quantifying the mental workload of simulated patients in clinical assessments ..... 19
Post breast cancer treatment lymphoedema .............................................. 19
Kidney health in indigenous Australians and New Zealanders ........................... 20
Vitamins and minerals in people with chronic kidney disease .......................... 20
Osteoporosis management in the digital age .............................................. 21
Use of medical mobile applications among clinicians .................................... 22
Use of medical mobile applications among general public .............................. 22
What should I do when my child is sick? Improving the management of common childhood ailments ............................................................................ 23
Lab-based Projects (involving Humans, Animals or in vitro Models) ........................ 24
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Research Projects in Respiratory Environmental Health and the Fetal Origins of Non-Communicable Disease ........................................................................ 24
Respiratory Environmental Health .......................................................... 24
Building tools to control the mind ........................................................... 26
DIY microscope system to illuminate subcellular compartments ....................... 26
Research Projects available in Molecular Neurobiology .................................. 27
How does calcium control the wiring of our brain? ....................................... 27
How is gene transcription regulated in neurons? .......................................... 28
What can we do about neuropathy? ......................................................... 29
How do oligodendroglial cells replenish their ER calcium stores? ...................... 30
Regulation of gene expression by the RUNX1 transcription factor ..................... 30
Regulation of gene expression in prostate cancer ........................................ 31
Genetic Determinants of Radiation Response in Prostate Cancer ...................... 31
Antimicrobial drug development ............................................................ 32
Investigation of an emerging pathogen ..................................................... 33
Carbohydrate metabolism in embryonic stem cells ....................................... 33
Enhancing neurogenesis to promote recovery following traumatic brain injury ..... 34
Tuberculosis .................................................................................... 34
Epigenetic machinery and mark alterations in transgenic AD mice .................... 35
Next-generation sequencing to map epigenetic profiles in the brain .................. 36
Viral Immunology Projects ........................................................................ 36
Induction of long-lived antiviral antibody responses by vaccination ................... 36
Novel approaches to treatment of viral pneumonia ...................................... 37
Mechanisms of protection of the host by virus-encoded TNF receptor homolog ..... 37
Mammalian and viral schlafen proteins: How do they affect the immune system? . 38
Studying human disease using human brain cells ......................................... 39
The role of pericytes and vascular function in health and disease ..................... 39
New animal models of human stroke ....................................................... 40
Division of Paramedicine .......................................................................... 41
Trauma and shock assessment using BSL, SI/MSI and Hb................................. 41
Use of end tidal CO2 (EtCO2) waveform capnography for evaluation and monitoring in spontaneously ventilating patients .......................................................... 42
Paramedic diagnostic accuracy in geriatric patients with complex co-morbidities .. 43
An evaluation of the correct use of paediatric restraint systems for children transported via ambulance ................................................................... 44
An evaluation of the preparedness of Australian ambulance services and/or paramedics to manage mass casualty incidents ........................................... 44
Projects offered by the Allergy and Anaphylaxis Research Group ...................... 45
Investigate community and out of hospital management of anaphylaxis to inform best practice guidelines within a multi-disciplinary health care environment ....... 45
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Currently underway but may be other possible aspects ................................. 46
Understanding hypothermia and hypoxia in unstable newborns born in the out-of-hospital setting ................................................................................. 46
Wicking Centre Neuroscience Honours Projects ................................................ 47
Wicking Centre Neuroscience Honours Projects ........................................... 47
Honours project in biomarkers of brain health ............................................ 47
CRISPR/Cas gene editing of human induced pluripotent stem (iPS) cells to investigate childhood-onset neurodegenerative diseases ................................ 48
Microglia in neurological diseases ........................................................... 48
Developmental maturation of proteins involved in Fragile X Syndrome ............... 49
Using electroencephalography to understand brain circuit abnormalities and sleep disturbances in Alzheimer’s disease model mice ......................................... 49
Understanding the role of stress hormones in Alzheimer’s disease (2 projects) ..... 49
Motor function deficits in mouse models of neurodegenerative disease .............. 50
Honours project in axon maintenance ...................................................... 50
Honours project in Motor Neuron Disease/frontotemporal dementia .................. 51
Wicking Centre Honours Projects in Care .................................................. 51
Health student understanding of dementia ................................................ 51
Dementia literacy research .................................................................. 52
Improving care for aged care home residents with dementia ........................... 52
Wicking Centre Honours Projects in Dementia Prevention .............................. 53
Relationships between risk factors for Alzheimer’s disease, memory performance and subjective memory complaints ......................................................... 53
The My INdex of DEmentia Risk (MINDER) Study........................................... 53
Barriers and enablers for brain healthy behaviours ....................................... 53
Masters of Public Health Research Projects .................................................... 54
Understand artificial intelligence and decision support to link laboratory with clinicians and patients ........................................................................ 54
Point of care testing of medication adherence: understanding the impact on ethics, socio-technical and patient-doctors relationship ......................................... 55
Social cultural factors influencing the implementation of healthy lifestyle in Tasmania community .......................................................................... 55
Curing hepatitis C? Exploring socio-cultural factors and understanding long term follow up of patients treated with DAA .................................................... 56
Can we beat liver cancer? Developing a patient-centred liver cancer screening strategy to improve outcomes of liver cancer in Tasmania ............................. 56
Pokémon Go and augmented reality games, and the impact on healthcare promotion for obesity related illness .................................................................... 58
Using anticipatory care and big data analytics to predict, design and transform future healthcare delivery ................................................................... 58
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The Honours degree provides students with the opportunity to undertake further training in research in biomedical sciences, clinical sciences, health services and population health. This is a year long program of advanced study that includes development of skills in understanding the scientific literature in biomedical and health fields, as well as the student’s aptitude in scientific writing and presentation. The critical element of the Honours year across all of our programs is the focus on students undertaking a major research project, which will involve learning research skills, conducting research on a relevant biomedical or health area and completing a thesis detailing and discussing the findings. The Honours year in the Division of Medicine research program is available to UTAS students who have completed an undergraduate degree in the BSc, BMedRes, BBiotech, BBiotechMedRes (or similar), three years of the MBBS program or a Bachelor of Paramedic Practice. Students from other institutions can also apply to do the program where they have completed similar degrees. Students can undertake projects, depending on their interest and academic background, in a broad range of areas including: • Biochemistry • Physiology • Anatomy • Neuroscience • Human genetics • Microbiology • The pathological sciences • Population and public health • Clinical trials • Paramedic practice An outline of available projects that the Division of Medicine (DoM) is offering in 2018 is contained in this booklet. If you cannot find a suitable project in here, or have a desire to undertake a project in a certain area or with a certain researcher, it is worthwhile contacting that researcher to discuss your idea. Often more projects are available, but are not been listed. More information about projects in affiliated centres such as the Wicking Dementia Research and Education Centre and Menzies Institute for Medical Research is available online. COURSE OBJECTIVES Students will undertake a supervised research project with an emphasis on advanced disciplinary knowledge, the use of specialised laboratory, fieldwork and/or statistical techniques relevant to their chosen research area, planning and conducting a scientific investigation and effective communication of research findings. Students will also gain experience in scientific writing and oral presentations. By the completion of the program, students should be able to write a scientific report to a standard acceptable for submission to a peer-reviewed journal, and deliverable at a relevant conference or scientific meeting.
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ACADEMIC REQUIREMENTS The compulsory components of the assessment for all Honours programs include a literature review as part of the thesis introduction, two seminar presentations, a thesis and a supervisors' report. One seminar presentation will be a critical review of a journal article and the second seminar presentation will be from your thesis. SCHOLARSHIPS There are a number of scholarships available to students undertaking research in the Division of Medicine. Scholarships are awarded based on academic merit. If you are an MBBS or Paramedic student, you can apply directly to the Division of Medicine using the application form available from [email protected]. This form will also be used to assess and approve your Honours application. For more information on availability, eligibility and how to apply for other scholarships, including those offered through the Menzies Institute for Medical Research, go to http://www.studentcentre.utas.edu.au/scholarships/. Please be aware that the CLOSING DATE for non-MBBS applications is 31 October. NB: for MBBS students the earlier date of 2 Sept 2017 applies, due to forward planning
considerations. YOUR APPLICATION TO DO HONOURS To apply to do Honours students should have completed three years of a relevant undergraduate degree with a credit average, or equivalent. It is a good idea before you apply to do Honours to identify a project that appeals to you and to make contact and discuss the project with the supervisor. Once you have decided to apply, go to ‘Future students’ on the UTAS website for information on the application process. To be successful in your application to study for Honours you will need to satisfy the Honours committee that you have a suitable project that constitutes the workload of an Honours thesis and that it can be accomplished within the time frame. In addition to this, the committee will need to be assured that the appropriate supervision is in place. Your application will also be judged on your past academic performance. All students need to apply online. If you are an MBBS student undertaking a project in the DoM you should complete the Honours application form that appears on the DoM research website page. Following approval of this application, you will be able to enrol in the Bachelor of Medical Science with Honours (M4N). Paramedic students in the Bachelor of Paramedic Practice with Honours (M4P) should also complete this same process. Undergraduate science students can enrol in the Bachelor of Medical Research with Honours (M4G), Bachelor of Biotechnology and Medical Research (K4L) or the Bachelor of Science with Honours (S4E) as appropriate.
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STUDENT EXPECTATIONS The course extends from late February (semester 1 commencement) to late October or mid-July (semester 2 commencement) to March or April the following year. Attendance requirements will be dictated by the nature of the research for example, whether the project is being undertaken within a hospital or within a laboratory. Attendance requirements are to be agreed upon between the student and supervisor. There is an expectation, despite the nature of the project, that the minimum time required to successfully complete the Honours year is a minimum of 40 hours per week equivalent to a standard full-time working week. The University and the Division of Medicine acknowledges that students are Division in extra-curricular activities and is generally supportive of students’ activities. The Division of Medicine must be confident that these activities do not significantly impact on the students’ ability to complete the requirements of the Honours year. For additional information regarding Honours contact Dr Steve Richards, the Course Coordinator. Contacts for projects supervised at other centres under Division of Medicine Honours are listed below. Menzies Institute for Medical Research projects are listed separately at: http://www.menzies.utas.edu.au/education/study-at-menzies/phd-and-honours NB: Below are listed projects available currently (as of August 2017). Further
projects will be added in November 2017. If you are interested in an area of research carried out by a Division of Medicine, Menzies or Wicking researcher that does not appear in this document, it may be worthwhile approaching them directly to see if they are considering supervising Honours projects in 2018.
COURSE COORDINATOR Dr Steve Richards: [email protected] Telephone: (03) 6226 2673 ADDITIONAL CONTACTS Dr Kathryn Ogden: [email protected] (Launceston) Telephone: (03) 6348 8790 Dr Peter Lucas [email protected] (Paramedic Practice) Telephone: (03) 6226 6952 Dr Anna King [email protected] (Wicking, lab-based) Telephone: (03) 6226 4817 Dr Kaylene Young [email protected] (Menzies Institute for Telephone: (03) 6226 7745 Medical Research)
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Clinical and Population Health based Projects (involving Human Subjects and/or Data)
Automated control of inspired oxygen therapy in neonates Supervisor(s): Professor Peter Dargaville ([email protected])
Dr Tim Gale ([email protected]) Avoidance of hypoxia (low blood oxygen level), and especially for the preterm neonate, hyperoxia (high blood oxygen level), is fundamental in the delivery of respiratory support to the newborn infant with respiratory insufficiency. Hypoxia in preterm infants is most commonly a consequence of respiratory distress syndrome, and, if not adequately treated, substantially increases the risk of mortality. Conversely, unrestricted and/or inadequately regulated oxygen therapy causes overgrowth of vasculature in the developing retina of the preterm infant. This retinopathy of prematurity (ROP) is a continuing problem in NICUs in the Western world, and is a significant concern in developing and newly industrialised countries. At present in most NICUs, moment-by-moment changes to FiO2 are under the control of the bedside staff, who make adjustments based on the transcutaneous oxygen saturation level (SpO2). Despite the best efforts of staff at the bedside, neonates on respiratory support spend considerable amounts of time with SpO2 readings outside the desired or target range. A study conducted at RHH in 2012 by UTAS MBBS Honours student Kathleen Lim (the SNOOT study) found that in preterm infants on non-invasive respiratory support, SpO2 was maintained in the target range only 31% of the time.1 The data collected in the SNOOT study1-3 have aided our efforts to develop an inspired oxygen controller. This is a device that receives transcutaneous oxygen saturation (SpO2) readings from a bedside oximeter, verifies and processes the oximetry data, compares the SpO2 readings with predetermined targets in a control algorithm, and sends signal pulses to a servomotor to automatically turn the FiO2 dial of a gas blender. The control algorithm at the heart of our control device has some unique features that have not been incorporated in FiO2 feedback control systems previously. We believe these additional features will allow more precise targeting of SpO2 in preterm infants receiving oxygen than ever before possible with an automated FiO2 control system. Preliminary studies of 4 h duration under controlled conditions, with a researcher present throughout, have been conducted in 2015 by our current UTAS MBBS Honours student, Gemma Plottier. We have found that in preterm infants our device appears to maintain SpO2 in the target range more effectively than manual control, with few episodes of hypoxia and hyperoxia. The next stage of development of the oxygen control device is a study (the SANTO-B study) in which automated control will be compared with manual control under standard clinical conditions for 24 h periods, without a member of the research team consistently in attendance. These studies will begin later in 2015, and will continue throughout 2016. The involvement of an MBBS Honours student in this next stage would be a great boost for the project, as has been the case in 2012 and 2015. Location: School of Medicine, Hobart
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References: 1 Lim K, Wheeler KI, Gale TJ, Jackson HD, Kihlstrand JF, Sand C, Dawson JA,
Dargaville PA. Oxygen saturation targeting in preterm infants receiving continuous positive airway pressure. J Pediatr (2014); 164:730-736.
2 Fathabadi OS, Gale TJ, Lim K, Salmon BP, Wheeler KI, Olivier JC, Dargaville PA.
Assessment of validity and predictability of the FiO2-SpO2 transfer-function in preterm infants. Physiol Meas (2014); 35: 1425-1437.
3 Lim K, Wheeler KI, Fathabadi O, Gale TJ, Dargaville PA. Lost without trace:
oximetry signal dropout in preterm infants. Arch Dis Child Fetal Neonatal Ed (2015); DOI: 10.1136/archdischild-2014-308108.
Overcoming the physiological effects of apnoea in preterm infants Supervisor(s): Professor Peter Dargaville ([email protected])
Dr Tim Gale ([email protected]) Project Description: The respiratory course for a very preterm infant during first hospitalization is most usually characterized by a protracted requirement for non-invasive respiratory support and oxygen therapy. This is a period of vulnerability, with reliance on an infant’s spontaneous respiratory effort to maintain cardiorespiratory stability at a time when respiratory pause events or apnoea are frequent. Apnoea (cessation of breathing for > 20 sec or > 10 sec if accompanied by physiological destabilisation) is a well-recognized cause of episodes of hypoxemia (low oxygen level) and/or bradycardia (low heart rate), which in turn appear to have lasting neurodevelopmental consequences in preterm infants.
Our combined Medical and Engineering research group (the “GREMLINS”)1 is investigating ways to better support and control the respiratory system of the preterm infant. In the past five years, and with the aid of three MBBS Honours students (Kathleen Lim, Gemma Plottier and Oliver Ladlow), along with numerous UTAS Engineering Honours students, we have developed and clinically tested a device to automatically control inspired oxygen concentration (FiO2) in preterm infants on continuous positive airway pressure (CPAP).2,3 This device, the function of which is under further study during 2017, shows a clear capacity to keep the oxygen saturation (SpO2) in the desired target range for more of the time than manual control of FiO2 by bedside staff. We have also begun to understand the factors that contribute to instability of SpO2 in preterm infants, with apnoea and loss of CPAP pressure being two major contributors. We have recently found that even brief pauses in breathing (5-9 sec in duration) are enough to cause significant hypoxic and bradycardic episodes in infants on CPAP. We are now investigating whether a similar feedback-controlled device can: i “cut short” a pause in breathing and thus avoid the physiological instability that
often follows, and/or ii deliver a brief pulse of increased oxygen to avoid or foreshorten a hypoxic event.
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A series of bench top and clinical studies is planned to investigate each of these questions. These studies will be conducted in 2018 and beyond in collaboration with UTAS School of Engineering, and will be largely based in the Neonatal and Paediatric Intensive Care Unit at the Royal Hobart Hospital. The involvement of 1-2 MBBS Honours students in these studies would be a great boost for each of them, as has been the case in 2012, 2015 and 2017. 1 GREMLINS: Group of Engineers and Medics Laboriously Investigating Neonatal
Systems. 2 Dargaville PA, Sadeghi Fathabadi O, Plottier GK, Lim K, Wheeler KI, Jayakar R,
Gale TJ. Development and pre-clinical testing of an adaptive algorithm for automated control of inspired oxygen in the preterm infant. Arch Dis Child Fetal Neonatal Ed 2017; 102: F31-F36.
3 Plottier GK, Wheeler KI, Ali SKM, Sadeghi Fathabadi O, Jayakar R, Gale TJ,
Dargaville PA. Clinical evaluation of a novel adaptive algorithm for automated control of oxygen therapy in preterm infants on non-invasive respiratory support. Arch Dis Child Fetal Neonatal Ed 2017; 102: F37-F43.
Patient-centred health care: Investigating the views of stakeholder groups Supervisor(s): Dr Kathryn Ogden, Senior Lecturer, Launceston Clinical School
Jenny Barr, Patient Partner Program Development and Strategy Director [email protected]
Project Synopsis: Patient-centredness in health care delivery recognises that patients’ values and preferences must be central in the delivery of care, both at the organisational and professional level. The notion of patient-centred care is not a new one with efforts to operationalise and study it dating back to at least as early as 1986. However, 30 years later patient-centred care remains somewhat of an enigma, with “many evangelists but few practitioners”1(p g7757) and ongoing debate and discussion as to the imperative for patient-centred care being taught and practiced and how it can be better achieved. Through previous work at the Launceston Clinical School, we have developed a conceptual map for ‘Patient-Centred Care Requirements.’ It outlines how an operational perspective to patient-centred care can be considered, refocussing attention towards ‘how’ to achieve patient-centred care. Our focus on ‘requirements’ aimed to lead to the complexity of patient-centred care delivery being better understood, thereby informing the definitions of patient-centred care in a more comprehensive way. One hundred and twenty three statements have been generated identifying elements required for patient centred care. This project will build on this work by collecting and analysing the views from five different stakeholder groups of each requirement statement regarding their relative importance, feasibility and how well they are achieved. Participants will be recruited
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from five stakeholder groups: patients and carers; clinicians’ health care managers; peak body representatives; and educators, and asked to rate each of the 123 statements contained in the Patient-Centred Care Conceptual Map on a 5 point likert scale according to importance, feasibility and how well they are achieved. Data will be collected using the CS Global Max online platform (http://www.conceptsystems.com/software/) and analysed to determine the stakeholder views on the elements of patient-centred care. Data will also be used to develop additional visual tools (pattern matches and go-zones) which will enable its use for education and training in a variety of settings. A further qualitative component may also be possible, but will not be crucial to achieve an honours level project, and can be negotiated depending on feasibility within the 12-month timeframe. Location: Launceston Clinical School Associated Scholarship:
The successful applicant will be able to apply for an additional scholarship from the Clifford Craig Medical Research Trust. Reference:
1 Hawkes N. Seeing things from the patients' view: what will it take? BMJ 2015;350:g7757. doi: 10.1136/bmj.g7757.
Heterologous effect of diphtheria, tetanus, acellular pertussis vaccination on influenza vaccine challenge in the elderly Supervisor(s): Associate Professor Katie Flanagan ([email protected])
Dr Kathryn Ogden ([email protected]) Research Project Synopsis: The world’s population is aging, with dramatic rises predicted in the coming decades; thus a healthy aging population is a major public health priority 1. However, the immune system declines with increasing age leading to increased susceptibility to infectious diseases, and suboptimal responses to vaccination, an ideal tool to prevent infections. Furthermore, it is increasingly acknowledged that childhood vaccines have major immune modulatory effects, beyond the induction of vaccine-specific immunity 2. Specifically, our previous studies demonstrate diphtheria-tetanus-pertussis (DTP) vaccine causes sex-specific immunosuppression and interferes with subsequent measles vaccine efficacy 1. However, the non-specific effects of vaccines, and their impact on the immune system of the elderly are an important, but as yet untouched, area of research. In this project will use state-of-the-art immunological tools to interrogate the complex relationship between the immune response to two vaccines recommended in the elderly in Australia, the seasonal influenza vaccine and DTP. This information will be used to provide the much needed evidence based rationale to implement optimal vaccination schedules in this vulnerable group.
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Study Aim Determine the effect of DTP vaccination prior to or co-administered with the influenza vaccine in the elderly on innate immunity. Methodology Elderly adults >65 years and healthy adults aged 30-50 years will be will be randomised prospectively into 1 of 3 vaccine groups at enrolment (see diagram below). Vaccines will be administered intramuscularly into the deltoid (different arms when both vaccines are given together). The design of the study indicating blood sampling (red circles) and vaccination time points for the three study groups. 30mLs venous blood (24mLs in heparin tubes, 2mLs in serum tube, 2mLs in EDTA) will be taken by the research nurse at the LGH Vaccine Trial Centre at the time points in the figure (circles). The project question will be addressed by culturing whole heparinised blood overnight with a panel of Toll-like receptor (TLR) ligands and whole killed pathogens. Culture supernatants will be collected and stored at -70°C for later multiplex cytokine analysis. The multiplex assays will be done in Melbourne. We anticipate ~150 subjects will be tested in this way. The student will also help with the recruitment, vaccination and bleeding of study subjects. They will also be trained in sample processing. Serum and plasma will be collected and stored from the remaining blood samples, and then peripheral blood mononuclear cells (PBMC) will be collected following density gradient centrifugation. We will also store PBMC in Trizol for later RNA extraction. Samples will be shipped intermittently to the Dept of Immunology and Pathology, Monash University in Melbourne for further analysis. Outcome The student will determine if the different vaccine schedules have an impact on innate immunity. Location: Vaccine Trial Laboratory, Launceston General Hospital and Systems
Vaccinology Trial Centre, Clifford Craig Medical Research Trust.
Blood 0 +24h 1wk 4wks +24h 5wks 8wk 28wks
GROUP 1 DTP Influenza
GROUP 2 Influenza DTP
GROUP 3 DTP/Influenza
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Associated Scholarship: The successful applicant will be able to apply for an additional scholarship from the Clifford Craig Medical Research Trust. References
1 M Steeper, M Plebanski, KL Flanagan. The global challenge of keeping the world’s aging population healthy by vaccination. Trans R Soc Trop Med Hyg (in press).
2 KL Flanagan, R van Crevel, N Curtis, F Shann, O Levy. Non-specific and sex-differential effects of vaccines: randomized controlled trials and emerging immunological mechanisms. Clin Infect Dis 2013; 57(2): 283-289 (PMID 23572484).
3 KL Flanagan and M Plebanski. Sex-differential heterologous (non-specific) effects of vaccines: an emerging public health issue that needs to be understood and exploited. Exp Rev Vaccines 2016, Epub (PMID 27362915).
4 F Noho-Konteh, JU Adetifa, M Cox, S Hossin, J Reynolds, MT Le, LC Sanyang, A Drammeh, T Forster, P Dickinson, P Ghazal, M Plebanski, H Whittle, SL Rowland-Jones, JS Sutherland, KL Flanagan. Sex-differential non-vaccine specific immunological effects of diphtheria-tetanus-pertussis and measles vaccination. Clin Infect Dis 2016, Epub (PMID 27436422).
How is chronic kidney disease identified and managed in general practice? (Students undertaking this project may be eligible for a scholarship aimed at projects undertaken at the Launceston Clinical School and within General Practice) Supervisor(s): Associate Professor Jan Radford (Associate Professor of General Practice,
UTAS) ([email protected])
Dr Kathryn Ogden (Research Fellow, UTAS)
Drs Rajesh Raj, Matthew Matthew and Duncan Cooke (renal physicians, Launceston General Hospital)
Research Project Synopsis Identifying patients in a general practice population at risk of developing chronic kidney disease (CKD) is an important part of preventative health care, as is optimally managing those with a diagnosis of chronic kidney disease. It is estimated that 10% of all adults presenting to a general practice in Australia have CKD, and 80% have at least one risk factor for CKD. Early intervention can reduce progression and cardiovascular risk by up to 50%, and may also improve quality of life. This study will contribute to knowledge on how to improve the detection and care of chronic kidney disease patients in general practice. Aims and Objectives: To determine how practices identify and record which of their patients have CKD and the accuracy of practice datasets.
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• To identify factors impacting on the accuracy of a practice database of patients with CKD including opportunities for improving record management.
• To explore factors involved in delivering optimal care to prevent progression of kidney disease and optimal management of established CKD.
Methodology This project will involve the systematic review of general practice patient records and surveys and interviews with a number of participating clinicians and patients. This approach will require an analysis of both qualitative and quantitative data. Location: Launceston Clinical School How can influenza vaccination of pregnant women be optimally delivered in general practice? Supervisor(s): Associate Professor Jan Radford (Associate Professor of General Practice,
UTAS) ([email protected])
Dr Kathryn Ogden (Research Fellow, UTAS) Research Project Synopsis Vaccinating pregnant women against influenza is now accepted as in important preventative health care activity. Ensuring that all pregnant women in a general practice population are vaccinated against influenza requires a systematic approach. How general practice monitors the delivery of this care has not been fully investigated. This project will contribute to knowledge on how to ensure systematic care is delivered to this potentially vulnerable population. Aims and Objectives This project aims to determine the prevalence of influenza vaccination among pregnant women within participating general practices and develop strategies for enhancing vaccine coverage, if needed. In order to achieve these outcomes the student will work with supervisors and general practice staff to identify: • Existing processes for recording both current pregnancy and influence vaccination
status within General Practice, and the accuracy of these processes,
• Factors impacting on the accuracy of coding for pregnancy and influenza vaccination status including whether and how accuracy can be improved through enhanced data management, and
• Barriers to the prescription and uptake of influenza immunisation during pregnancy.
Methodology This will be a mixed methods study involving a systematic review of clinical records and surveys and interviews with participating GPs, other practice staff and patients. Both
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qualitative and quantitative skills will be developed during the analysis of clinical record data and the development and analysis of survey and interview data. Location: General Practices in the Launceston region and the Launceston Clinical
School How do GPs implement treatment guidelines in patients with a pre-existing condition? Supervisor(s): Associate Professor Jan Radford (Associate Professor of General Practice,
UTAS) ([email protected])
Dr Kathryn Ogden (Research Fellow, UTAS) Research Project Synopsis General Practitioners are bombarded with treatment guidelines and recommendations to treat to target for many conditions. This project will look at how a single aspect of an updated guideline is implemented in General Practice, concurrent with ongoing management of patient with pre-existing coronary heart disease. In August of 2012 the Heart Foundation updated their secondary risk prevention guide with a new target for treating elevated low-density lipids (LDL) from 2.0mmmol/L to a new target 1.8mmol/L. This project will explore how GPs apply new treatment targets to pre-existing patients. Aims and Objectives: • To determine how practices identify and record patients diagnosis of coronary heart
disease, and
• To explore the factors involved in modifying practice in order to deliver optimal care as determined by updated guidelines.
Methodology An audit of patient records will be used to identify the study population and determine what proportion have been diagnosed and are being actively managed. Surveys and interview will be conducted with clinicians and patients in order to determine their knowledge of and attitudes towards the implementation of updated guidelines. Both qualitative and quantitative skills will be developed during the analysis of clinical record data and the development and analysis of survey and interview data. Location: Launceston Clinical School
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Using advanced imaging to gain a better understanding of hand osteoarthritis Supervisor(s): Dr Dawn Aitken (Senior Research Fellow) [email protected]
Dr Kathryn Squibb (Research Fellow and Radiographer) [email protected]
Professor Graeme Jones (Professor of Rheumatology and Epidemiology and Head of the Musculoskeletal Unit)
Research Project Synopsis and Aims This project aims to gain a better understanding of hand osteoarthritis using advanced imaging modalities including x-ray, MRI, ultrasound, and micro-CT scanning. 200 older Tasmanian’s between the ages of 60 – 90 years were enrolled in the study. They have provided information about hand symptoms, including pain and dysfunction and have undergone extensive scanning including x-ray, MRI, ultrasound, and a new novel micro-CT assessment to assess bone architecture. The aims of this study include: • To examine the relationship between symptoms and structural abnormalities
measured using x-ray, MRI, ultrasound, and micro-CT.
• To explore the association between structural abnormalities measured using each modality including bone marrow lesions, osteophytes (bony growths), joint space narrowing, and inflammation.
Ultimately this project will provide a better understanding of the pathology of hand osteoarthritis and aims to provide insight into the onset and progression of the disease. This work is highly suitable for somebody with an interest or background in musculoskeletal health. Location: Menzies Institute for Medical Research, Hobart Translational Health Services Research The Translational Health Services Research team is interested in many aspects of the experience of people with dementia and their carers over the course of the condition. Our research interests include the challenges of diagnosis, the delivery of clinical care, in the community, hospitals and residential aged care settings. The team investigates ways to meet future workforce needs, which includes delivering and evaluating better education to health professionals, and programs of care to people with dementia and their families. Our work contributes to the understanding of the translation of research into practice. The Understanding Dementia Massive Open Online Course continues to attract large numbers of participants generating a wealth of data about those who participate and use the course content. The research team follow various methodologies to answer research questions of interest including systematic literature reviews, cross sectional, longitudinal and quasi experimental designs, the design and development of new measures, mixed methods and action research. If you are interested in discussing a project with the Translational Health Services Team please contact Kathleen Doherty on [email protected].
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Unnecessary variation in hospital length of stay: are we causing more suffering and how do we prevent it? Supervisor(s): Dr Nicole Hancock, Head of Department of General Medicine, Royal
Hobart Hospital ([email protected])
Dr Jim Stankovich, statistician, Health Services Innovation Tasmania, Faculty of Health ([email protected])
Research Project Synopsis Suppose you are admitted to hospital with pneumonia. Ideally, how long you spend in hospital should only depend on how sick you are. But sometimes other factors come into play. For example, there may be no beds free in the "home ward" where pneumonia patients normally go, so you have to go to the cardiology ward instead. This may mean that you wait longer for your doctor or your dietician to see you, or for some blood tests to be completed. Nobody wants to stay in hospital longer than they have to; it is also a waste of money and resources. As part of a program to improve processes for medical patients at RHH, we are interested in understanding this sort of unwanted variation in length of stay (LOS). Analysing the medical records of 8972 medical patients admitted at RHH over two years, we found that LOS is • 38% longer for patients who aren't admitted to a home ward (ie “outlier" patients),
and
• 14% longer for patients admitted on a Friday compared to patients admitted on a Monday.
The aim of the project is to understand more about this variation in LOS when considering outlier patients and those admitted on different days of the week. Are there subgroups of patients that will suffer more than others? Is there a positive or negative correlation between LOS and probability of being readmitted to hospital? Is it possible to change some hospital work practices to improve these patients’ care? Depending on the student's interests and skills the research will comprise all or some of the following: statistical analysis of quantitative data, reading and interpreting case notes, and observing and speaking with hospital staff. Location: Medical Science Precinct (Hobart), Royal Hobart Hospital ASPREE. A double-blind randomised controlled trial of low dose aspirin for primary prevention in the aged Supervisor: Professor Mark Nelson ([email protected]) Research Project Synopsis ASPREE is a double blind randomised placebo-controlled trial that is investigating whether aspirin can prolong good health and maintain independence amongst older people. The study will involve men and women over 70 years of age who are free from
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cardiovascular disease, or dementia. Already 16,702 participants have been enrolled in this study in Australia, 886 in Hobart, 554 Launceston and 664 in North-West Tasmania. Opportunity now arises with the locking of the baseline data to answer important questions relating to this very large community based cohort. ASPREE Healthy Ageing Biobank Supervisor: Professor Mark Nelson ([email protected]) Research Project Synopsis The ASPREE Healthy Ageing Biobank is an initiative in which blood and urine samples will be collected from healthy participants, aged 70 and over, who have provided consent to participate in the ASPREE Clinical Trial. Participants in the Biobank will be followed for a period of five years, and may then provide a second blood and urine sample at the conclusion of the study. We have 12,200 baseline samples and will likely collect 9000 participant samples at 3 years into the study. Opportunity arises for requesting samples to answer important clinical questions. A randomised clinical trial of STAtin therapy for Reducing Events in the Elderly (STAREE) Supervisor: Professor Mark Nelson ([email protected]) Research Project Synopsis STAREE is a double blind randomised placebo-controlled trial that is investigating whether statins can prolong good health and maintain independence amongst older people. The study will involve men and women over 70 years of age who are free from cardiovascular disease, diabetes or dementia. This study is just starting in Tasmania and the opportunity is to gain experience in the conduct of a large community trial (18,000). Acute pancreatitis admissions in Hobart Supervisor: Professor Richard Turner ([email protected]) Research Project Synopsis A prospective database of acute pancreatitis admissions to the Royal Hobart Hospital (and possibly private hospitals) will be developed. This will consist of independent variables that may include the usually obtained parameters from clinical records, as well as a variety of novel anthropometric and nutritional measures that the researcher would obtain by seeing the patients themselves. Dependent (outcome) variables would include severe acute pancreatitis (including death), a diagnosis of co-existing chronic pancreatitis, length of stay, and other clinical outcomes. Analysis of the data will yield
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possible determinants of the stated disease outcomes that may ultimately inform evidence-based clinical practice. The database may also lead to other projects derived from longitudinal follow-up of patients. Location: School of Medicine and Royal Hobart Hospital Quantifying the mental workload of simulated patients in clinical assessments Supervisor: Professor Richard Turner ([email protected])
Psychologist from Wicking Institute or School of Medicine Psychology Program)
Brief Description While some work has been done to objectively measure the cognitive and perceptual workload of Examiners involved in live clinical assessments such as OSCEs, there is scant information on the impact of such assessments on, and implications for, Simulated Patients (SPs). The consistency and authenticity of this group of people is essential in ensuring valid and reliable assessment. The project will use one or more validated psychometric tools to quantify the mental workload for SPs in OSCE stations. Analysis of the data will seek determinants of mental workload, with a view to optimising training and working conditions. This will ultimately contribute to the continuous quality improvement of clinical assessment. Post breast cancer treatment lymphoedema Supervisor(s): Dr Barry Edwards ([email protected])
Dr Mary Self ([email protected]) Professor Richard Turner ([email protected])
Research Project Synopsis This study aims to assess the prevalence and severity of upper limb lymphoedema following treatment for breast cancer, and to seek determinants for this. Women with a previous diagnosis of breast cancer will be recruited to have assessment by volumetric water displacement. Potential determinants will be sought by means of a questionnaire and review of relevant case notes. This study will be of particular interest in terms of assessing the impact of the recent trend to perform sentinel lymph node biopsies rather than axillary clearance. Location: School of Medicine, Hobart
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Kidney health in indigenous Australians and New Zealanders Supervisor(s): Dr Matthew Jose ([email protected]). Menzies Institute for
Medical Research and RHH Dialysis Unit Research Project Synopsis Indigenous people in Australia and New Zealand experience rates of ESKD several times higher than non-indigenous people. Treatment with dialysis or a kidney transplant is becoming increasingly common, but outcomes are still suboptimal. Five years after a kidney transplant, more than half of all kidney transplants in Aboriginal recipients are no longer functioning (compared to only 20% of non-Aboriginal Australians) and nearly 40% of Aboriginal recipients are dead (compared with only 11% of non-Aboriginal Australians). The aims of this project are: • To examine factors that influence the outcomes of Indigenous people treated with
dialysis through the ANZDATA registry
• To examine factors associated with poor outcome in Indigenous kidney transplantation
Location: Menzies Institute for Medical Research and the Royal Hobart Hospital
Dialysis Unit Vitamins and minerals in people with chronic kidney disease Supervisor(s): Dr Matthew Jose ([email protected]). Menzies Institute for
Medical Research Tasmania and RHH Dialysis Unit Research Project Synopsis People with chronic kidney disease have low blood levels of vitamin B, C & D. 25-hydroxy vitamin D is lower than in people without kidney disease, 1,25- hydroxy Vitamin D is low in nearly all people with end-stage kidney disease. Vitamin B & C are water-soluble vitamins that are washed out by the process of dialysis. Despite these low levels, there is very little knowledge about replacement. This project will examine these vitamins in people on dialysis and the effect of vitamin replacement. The aims of this project are to: • Identify the prevalence of vitamin deficiency in Tasmanians with CKD
• Examine the effects of vitamin replacement Location: Menzies Institute for Medical Research and the Royal Hobart Hospital
Dialysis Unit
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Osteoporosis management in the digital age Supervisor(s): Dr Kenneth Lee ([email protected])
Dr Li-Shean Toh ([email protected]) Research Project Synopsis: The Internet has rapidly become an invaluable source of health information. Approximately 80% of Australian Internet users utilise the Internet for health-related activities. Similar figures relating to online health information usage is seen in a number of countries across the globe. Additionally, the ‘app’ market is rapidly growing, with well over 150,000 health-related apps ranging from simple diary/activity trackers and information references to disease diagnostics, screening, and prevention tools. Surely both patients and health professionals are making use of this abundance of digitally-based support … or are they? Throughout the developed nations, there is a commonality: our populations are ageing. The increase in the elderly population coupled with the association between osteoporosis and fractures makes the condition a significant global health concern. As such the incidence of osteoporotic fractures is predicted to increase, from one in every 8.1 minutes in 2001 to one in every 3.7 minutes in 2021. A prior fragility fracture increases the risk of subsequent fractures, morbidity, and premature death. Economically, the disability due to osteoporosis in Europe is greater than that caused by cancers. In Australia, osteoporosis is one of the national health priority conditions, and it affects 1 in 10 Australians aged 50 years and above. Ignorance about osteoporosis is still common among health professionals, patients, and the public at large. Given the abundance of online and digital resources available, often at low or no cost, it is prudent to explore technological options to more effectively support osteoporosis healthcare delivery and management. Aim To systematically evaluate the global landscape of online and digital resources used in osteoporosis management. Methodology The honours student will: 1 Develop a search strategy with assistance from their supervisors and a
medical/health research librarian. 2 Learn to register a systematic review protocol. 3 Perform a systematic review in accordance to established guidelines for the
conduct of systematic reviews. 4 Report a systematic review following PRISMA guidelines for reporting of systematic
reviews. 5 Aim to produce a sound review suitable for publication in a quality peer-reviewed
journal – in doing so, the student will gain first-hand insight into the peer-review process.
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Use of medical mobile applications among clinicians Supervisor(s): Dr Long Ming ([email protected])
Dr Tabish Zaidi ([email protected]) Research Project Synopsis Handheld computers (HHCs) such as smartphones and tablets are providing a variety of drug information (DI) applications to assist clinicians’ decision making in the clinical and hospital setting. However, little is known about the extent of their use among Australian clinicians. The study is aimed to assess the use of electronic DI resources via HHCs by clinicians in Australia. This study also aimed to investigate the clinicians’ perception toward the DI content and functions of mobile medical applications. Methods
A convenience sampling method will be adopted to invite clinicians working in various sectors such as hospitals, and clinics to participate in this online survey. A validated questionnaire will be administered, and data will be summarized and presented using descriptive statistics. Potential Benefit
We will understand the type and frequency of DI search among clinicians in Australia. We will uncover features of a good mobile app and provide information for the development of a locally produced DI sources.
This project is suitable for BMedRes, Paramed, BSc students.
Location: School of Medicine, Hobart Use of medical mobile applications among general public Supervisor(s): Dr Long Ming ([email protected])
Dr Tabish Zaidi ([email protected]) Research Project Synopsis Due to the wide use and improved functionality of smartphone, e-health apps which are accessible on mobile platforms made mobile health (mHealth) an easy way for general public to seek health information. mhealth is a term use to describe mobile computing, medical sensor, and communications technologies for health-care. It is one of the approaches for health care authority to educate general public on healthcare and well-being services. mHealth application has not proven could improve the healthcare services for elderly in United States. mHealth serves a significant purpose in current and future healthcare delivery and yet research on its use among Australian community is scarce. The study is aimed to assess the use of medical mobile applications by general public in Australia. This study also aimed to investigate the public perception toward the drug information content and functions of mobile medical applications.
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Methods A convenience sampling method will be adopted to invite Facebook users to participate in this online survey. A validated questionnaire will be administered, and data will be summarized and presented using descriptive statistics. Potential Benefit We will understand the type and frequency of use of medical mobile applications and drug information search among general public. This project is suitable for BMedRes, Paramed, BSc students. Location: School of Medicine, Hobart What should I do when my child is sick? Improving the management of common childhood ailments Supervisor: Dr Bonnie Bereznicki ([email protected]) Project Synopsis Parents are understandably concerned when they have a sick child, and often have difficulty assessing the severity of the illness. Furthermore, lower levels of parental knowledge increase the risk of inappropriate medication use and unnecessary contacts with the healthcare system. Recent Australian and Tasmanian hospital statistics indicate that infants and young children are among the highest users of Emergency Departments (EDs), and a high proportion of these presentations are for non-urgent ailments.1-3 Fever, a main indicator of illness, often creates undue anxiety among parents, and can interfere with the parent’s ability to accurately observe the general wellness of their child. Initial research has focused the burden of childhood fever on the Royal Hobart Hospital ED and Australian families. Preliminary findings demonstrate that childhood fever may place an unnecessary burden on the RHH ED, with the majority of presentations not requiring any hospital care. Moreover, the average time spent in the ED for these cases is over an hour longer than the state average for non-admitted ED cases.4 Further findings from a national survey of over 10,000 parents suggests that parental knowledge and fever management practices are far from optimal, with more than 50% of respondents unsure what temperature constitutes a fever, unnecessarily administering medication to reduce unfounded ‘dangers’ of a fever, with one-third reporting that they had previously called an ambulance or taken their children to hospital for a fever.4 The next step in this research will be to investigate how this burden can be reduced through improved parental education, as well as expanding the research to include other areas of child health. Specific projects will be discussed with students upon contact.
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References 1. Australian Institute of Health and Welfare. Emergency department care 2014–15:
Australian hospital statistics. Health services series no 65. Cat no HSE 168. Canberra: AIHW; 2015. Available at: http://www.aihw.gov.au/publication-detail/?id=60129553619 [accessed June 2016].
2. Australian Bureau of Statistics. Australian Demographic Statistics, Dec 2015. Available at: http://www.abs.gov.au/ausstats/[email protected]/mf/3101.0 [accessed June 2016].
3. Freed G, Gafforini S, Carson N. Age-related variation in primary care-type presentations to emergency departments. Aust Fam Physician 2015; 44(8): 584-588.
4. Bereznicki B, Beggs S, Zosky G, Bereznicki L. Investigating the burden of childhood fever on Tasmanian families and the Royal Hobart Hospital’s Emergency Department (2016). Unpublished raw data.
Lab-based Projects (involving Humans, Animals or in vitro Models)
Research Projects in Respiratory Environmental Health and the Fetal Origins of Non-Communicable Disease Supervisor(s): Associate Professor Graeme Zosky ([email protected])
Dr Renee Dwyer ([email protected]) Dr Ling Chen ([email protected])
Research Overview The environment that we are exposed to has a significant impact on our health. Our response to these exposures is dictated by a range of factors including the nature of the exposure (eg acute vs chronic), the timing of the exposure (in utero vs post-natal) and the individual (eg age, sex, health status). We have a range of projects that aim to:
1 fill the gaps in our understanding of the impact(s) of common environmental exposures on health and
2 identify the mechanisms underpinning epidemiological associations between environmental exposures and health outcomes.
Much of our research is focussed on respiratory health, with an emphasis on the effects of maternal exposure on offspring, but we also have parallel research streams exploring metabolic and neurological outcomes. Respiratory Environmental Health
The respiratory health effects of iron oxide particles
The particles in the air that we breathe have well-known detrimental impacts on respiratory health. In order to mitigate the health effects of these particles there are National air quality guidelines. However, these guidelines are based almost entirely on particles that are found in urban environments which are primarily derived from
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combustion (eg diesel) sources. This ignores that fact that a large proportion of the population lives in environments where the primary source of particles is geogenic (earth-derived). We have a wealth of data demonstrating that geogenic particles have a detrimental impact on respiratory health and that the iron content of the particles is a critical determinant of the response. We have a range of projects examining how iron oxide particles impact on the respiratory response to infection and how different cell types within the lung orchestrate the response to these particles. Health effects of the Hazelwood coal fire
In February-March 2014 an open-pit brown coalmine fire burned for six weeks adjacent to the town of Morwell, Victoria. Environmental sampling in the Latrobe Valley during the fire clearly demonstrated high levels of exposure to the smoke from this fire in the community. The recent Hazelwood Mine Fire Inquiry Report identified a suite of pollutants associated with the fire emissions including carbon monoxide, particulate matter, nitrogen dioxide, sulphur dioxide, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds, dioxins and furans, and heavy metals. Each of these pollutants has been linked to adverse health effects. In particular, there is significant concern regarding the health impact(s) on children born to mothers who were exposed to the emissions. We are currently running a series of mechanistic and toxicological lab based studies, to complement a large epidemiological study, into the respiratory health effects of these particles and the physico-chemical characteristics of the particles that are the most detrimental to lung health. Fetal origins of non-communicable disease
Chronic lung disease
For many years we have been interested in the effect(s) of maternal environmental exposures on fetal lung development and how this influences the susceptibility to lung disease later in life. For example, we have shown that arsenic contamination of drinking water impairs lung development, airway growth and exacerbates the response to respiratory viral infection. Similarly, we have been instrumental in demonstrating the importance of vitamin D for normal lung development which has inspired public interest in this area. We have a large biobank of tissue samples from our mouse model studies on these issues and are keen to further explore the mechanisms linking maternal exposure with the susceptibility to chronic lung disease in these samples. Maternal vitamin D deficiency
As outlined above, we have a biobank of lung samples associated with maternal vitamin D deficiency. In addition to these lung samples we have brain, liver, vascular and placental tissue which means we have the opportunity to assess the impact of in utero vitamin D deficiency on a range of organs. In some of these studies we have also exposed mice to high and low fat diets which allows us the opportunity to assess how maternal exposure interacts with post-natal metabolic disease. This work has broad implications for public health. Projects Honours projects can be negotiated within the scope of the research program outlined above. Contact Associate Professor Zosky to discuss. Location: School of Medicine, Medical Science Precinct
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Building tools to control the mind Supervisor(s) Dr John Y Lin ([email protected])
Associate Professor Lisa Foa ([email protected])
The activities of individual and/or ensembles of neurons in the brain control the behaviour of higher level organisms from the flatworms to human. The ability to precisely manipulate the cellular activities or signalling pathways used by neurons in both space and time can reveal how cellular activity is related to the behaviour of awake animals – providing insights into the functioning of the mind. The goal of the project is to build protein-based tools that can be used to precisely manipulate cellular activities with light. This can ultimately be used to manipulate cellular activity in selective neurons and control the behaviours of laboratory animals. Why use light instead of pharmacological agents? It is totally exogenous from the brain, easy to manipulate precisely within the tissue and have minimal side effects. It also does not cost a lot of money and you cannot spill it on the bench. What are the cellular activities that we are interested in manipulating with light? We are interested in vesicular synaptic release and G-protein coupled receptor pathways such as Gαi, Gαs, Gαq, phospholipase C, protein kinase C and adenylate cyclase (you can take your pick), which are known to be associated with the chemical communication between neurons and modulate behavioural outcomes. The activities involved in the project: reading, designing your proteins, PCR and DNA gels, molecular cloning, cell culture, microscope work, electrophysiology, breaking things (both intentional and unintentional), building things, biochemical and biophysical characterisation and some thinking would be good. What is the expected outcome? You will learn something about molecular biology, biochemistry, biophysics, optics, electronics and graduate with an experience of doing a different kind of scientific project. DIY microscope system to illuminate subcellular compartments Supervisor(s): Dr John Y Lin ([email protected])
Dr Robert Gasperini ([email protected])
Microscopes are essential parts of life science research. Most researchers use one but not many of them know how to build one. For this reason they can be very expensive and can cost more than your house. What is a microscope really? There are lenses to collect and focus light, a light source that provide light, and a light capturing device for making the image (sometimes these are your eyes, sometimes these is a camera). If it is a fluorescence microscope, you need filters to select for the right wavelengths of light and a strong light source to provide the excitation wavelength. Is it possible to build one or modify an existing one at lower cost? It won’t be fancy but it is possible. Can you make one with laser and epifluorescence capacity? This is harder but doable. Are you up for a challenge to do a DIY project that is a little different from your regular biomedical research? The goal is to build or modify an existing microscope that will let us do epifluorescence imaging and also incorporate a dual mirror galvanometer and/or
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DMD/DLP (digital mirror device/digital light projection) system that gives us the capacity to spatially and temporally control the illumination to a small part of field of view. We will then incorporate this system to selectively manipulate light-responsive proteins in the cells expressing protein-based tools to control cellular response in subcellular location. The goal will be to incorporate this microscope system with the current research in the laboratory to modulate cellular activities in subcellular region. If successful, we will test several of our existing tools to see whether we can limit the manipulation of cellular activities within specific cellular compartments. The activities involved in the project include reading, learning about optics, building things on a breadboard, optic alignment, laser alignment, writing (or finding existing) computer codes, electronics and cell culture. What is the expected outcome? You will learn a lot about optics and why off-the-shelf microscope cost so much. If the project is going really well we will get to do some really cool validation and testings in real cells. You will also learn about cell biology and when you complete the project. Research Projects available in Molecular Neurobiology Supervisor(s): Associate Professor Lisa Foa ([email protected])
Dr John Lin, ([email protected]) Professor David Small ([email protected]) Dr Kaylene Young [email protected]
Location: School of Medicine, UTAS and the Menzies Institute for Medical Research How does calcium control the wiring of our brain? Supervisors: Associate Professor Lisa Foa ([email protected])
Dr Robert Gasperini ([email protected]) Research Project Synopsis We all walk around with super-plastic computers inside our skulls, called a brain. The brain is better, faster than a computer though. It can learn with experience, change in response to our environment, our diet, our life. Incredibly, the basic circuitry of our brain is laid down during embryonic and early life. We have very little understanding of how this process occurs during normal development, yet understanding such developmental processes is vital, not only for understanding the developmental disorders of the brain, such as autism, but also for understanding how we might re-connect the circuitry of the brain and spinal cord after trauma.
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The precise connectivity of the human nervous system develops as young developing neurons send out processes, or axons, to connect with their target cells. At the distal tip of extending axons are growth cones (pictured), dynamic motile structures, which guide the developing axons. In this process, known as axon guidance the growth cones navigate the embryonic milieu, detecting, interpreting and responding to a multitude of guidance cues. Aberrant axon guidance is thought to be an important causative factor in several neurodevelopmental disorders such as autism and mental retardation syndromes.
Deciphering the molecular mechanisms that regulate axon guidance will improve our understanding of these disorders. It is also hoped that an improved understanding of axon guidance will advance the cause of neuronal regeneration after injury. Calcium signalling is known to be vital for growth cone navigation. Too much or too little calcium can cause growth cone collapse. However the molecular mechanisms that regulate calcium signalling are unclear. We have several projects in our laboratory that examine which proteins function to control calcium signalling in the growth cone and, importantly, how those calcium signals control the growth cone cyotoskeleton. Because controlling the cytoskeleton means controlling growth cone navigation and hence wiring of the brain. Our work centres around live-cell imaging to determine what controls growth cone navigation. We use growth cones from sensory neurons in vitro, where we examine growth cone navigation in response to traditional and novel guidance cues; we use in vivo imaging to examine growth cone navigation as they grow through the cellular milieu of the embryonic zebrafish. We can image calcium signaling in real time and manipulate the activity of the neurons using light (in collaboration with Dr John Lin). Through our work we are deciphering new mechanisms of calcium regulation, and uncovering novel signalling mechanisms that control growth cone navigation in the developing nervous system. How is gene transcription regulated in neurons? Supervisors: Associate Professor Lisa Foa ([email protected])
Dr Robert Gasperini ([email protected]) Dr Adele Holloway ([email protected])
Research Project Synopsis Gene regulation is a fundamental aspect of normal growth and differentiation of all cells. Mechanisms of neural development are crucially dependent on the orchestrated expression of genes in a timely and coordinated fashion. Errors in gene transcription are a feature of a number of neurodevelopmental syndromes such as autism and increasingly the role of transcription is being recognized in diseases such as depression. However, our knowledge of the mechanisms that regulate gene transcription within neurons is very limited. This project aims to examine the role of a protein family known as Homer in the regulation of gene transcription in neurons. Certain calcium signals are known to activate gene transcription in neurons and we hypothesize that Homer proteins integrate these calcium signals, regulating their transmission to the nucleus. We have
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found that Homer can modulate the activity of an important transcription factor known as NFAT. This project involves examining the interaction between Homer, calcium and NFAT. Several students could work on this project since there are multiple aspects of the project, including protein structure studies, live cell imaging and gene transcription assays. Studies will include methods for molecular biology, tissue culture, live cell imaging and protein biochemistry. What can we do about neuropathy? Supervisors: Dino Premilovac ([email protected])
Associate Professor Lisa Foa ([email protected]) Dr Robert Gasperini ([email protected])
Research Project Synopsis One of the major complications of long term diabetes is peripheral neuropathy – nerve damage. There is currently no treatment for neuropathy, which affects more than 50% of all those with diabetes. Diabetic neuropathy occurs particularly in the skin, where nerve fibres retract into the dermis leading to either a loss of touch sensation, loss of thermal sensation, or hyper-sensation resulting in chronic pain, or a combination of these defects. It is also believed to be one of the triggers for the formation of ulcers (and detection of ulcers by those affected due to lack of sensation) and is the leading cause of amputation and hospitalisation among those with diabetes. In humans, type 2 diabetes takes decades to develop and peripheral neuropathy is usually present at the end of the disease process resulting primarily in response to chronic hyperglycaemia. Due to the long timeframe, it is difficult and time-consuming to fully reproduce the disease progression in lab animals without the use of pharmacologic agents. The first aim of this project will be develop a new animal model diabetic neuropathy. Our aim is to better understand the process of the disease and to use this model to test novel therapeutics. Our work on growth cone navigation in vitro has led to the discovery of a novel signaling system that may enhance neuronal regeneration after a neuropathy. One of the most important things with regeneration is that the axons grow back to the correct sites, rather than inappropriately branching or sprouting. Such inappropriate sprouting can cause allodynia, which is a painful response to a stimuli that shouldn't normally hurt (like a light touch hurts sunburnt skin). Our ultimate aim is to establish a model where we can guide regenerating axons back to their correct location in the skin, reconnecting functionally, thereby reducing pain.
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How do oligodendroglial cells replenish their ER calcium stores? Supervisors: Dr Kaylene Young ([email protected])
Dr Rob Gasperini ([email protected]) Associate Professor Lisa Foa ([email protected])
Research Project Synopsis Oligodendrocyte progenitor cells (OPCs) are the largest proliferating cell population in the adult brain, comprising ~5% of all brain cells. The function of these cells is to generate new oligodendrocytes in the normal brain, and contribute to remyelination in response to a demyelinating disease such as multiple sclerosis. It was recently discovered that neurons form synapses onto OPCs, and that neuronal activity can influence OPC behaviour. But how this occurs is largely unknown. As neuronal activity has been shown to evoke a calcium signal within OPCs, we hypothesise that calcium signalling directs OPC behaviour, and will be reliant on calcium release from the endoplasmic reticulum (ER). We will examine OPCs and oligodendrocytes in vitro and in vivo to determine which components of the calcium-induced calcium release pathway are active in each cell type, their sub-cellular localisation, and whether their manipulation can prevent or promote oligodendrocyte differentiation. This project aims to determine the mechanism by which calcium signalling is regulated within OPCs.
Location: School of Medicine, Medical Science Precinct Regulation of gene expression by the RUNX1 transcription factor Supervisor: Dr Adele Holloway ([email protected]) Research Project Synopsis A significant proportion of leukaemias contain genetic lesions that generate altered forms of a protein called RUNX1 (or AML1). RUNX1 controls the expression of genes involved in blood cell growth and it is proposed the abnormal forms of RUNX1 drive aberrant gene expression leading to the development of leukaemia. Our work suggests the abnormal RUNX1 proteins act by generating epigenetic changes within cells and we are focussed on characterising these epigenetic changes. The characterisation of these epigenetic changes is of great interest because while genetic lesions that cause cancer are currently not reversible, epigenetic changes can potentially be reversed by pharmacological intervention, providing promise for the treatment of these leukaemias as well as other cancers caused by epigenetic changes. Our current research therefore aims to investigate how the altered forms of RUNX1 found in leukaemic cells direct epigenetic changes to these genes. Research projects in this area involve a range of molecular and cell biology techniques investigating putative RUNX1 target genes we have identified following microarray analysis of cells in which RUNX1 was disrupted. Techniques will include cell culture, cloning gene promoters into reporter plasmids and monitoring reporter activity and
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analysing the chromatin structure and expression of immune genes using real-time PCR based assays. Location: School of Medicine Regulation of gene expression in prostate cancer Supervisor(s): Dr Adele Holloway ([email protected])
Dr Jo Dickinson ([email protected]) Research Project Synopsis Prostate cancer diagnoses continue to rise rapidly in Australia, but of most concern is our current inability to distinguish aggressive tumours with propensity to metastasize from more indolent disease. We thus urgently require a better understanding of the underlying drivers of this disease, and particularly the factors and mechanisms that drive the transition to more aggressive tumours with a propensity to spread. These factors may represent biomarkers and potential therapeutic targets in prostate cancer progression. Integrins are cell surface receptors that play important roles in cell proliferation, differentiation, survival and migration, and thus play a key role in cancer development and progression. Our current research therefore aims to: • investigate the transcriptional and epigenetic regulators of integrins in normal
cells, and
• determine how expression of integrins is altered in prostate cancer cells. Techniques utilised in this work include cell culture, cloning, gene expression analysis and PCR based techniques to determine methylation. Location: School of Medicine and Menzies Institute for Medical Research Genetic Determinants of Radiation Response in Prostate Cancer Supervisor(s): Dr Jo Dickinson ([email protected])
Dr Kate Brettingham-Moore ([email protected]) Dr Adele Holloway ([email protected]) Dr Jac Charlesworth ([email protected]) Dr Jim Stankovich ([email protected])
Research Project Synopsis Currently patients presenting with locally advanced prostate cancer are provided with a number of treatment options including brachytherapy, prostatectomy, High Intensity Focused Ultrasound, hormone therapy and radiotherapy. External beam radiotherapy (RT) is commonly used in combination with hormone therapy as an alternative to or in combination with surgical resection of the tumour. The biochemical failure rate of RT
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for prostate cancer patients is around 40-50% within 5 years of treatment. Thus a significant proportion of patients derive no survival benefit from this treatment yet are exposed to the significant toxic treatment side-effects. Thus there is an important need to identify patients unlikely to benefit from RT to help direct them towards alternate and ultimately more successful treatment options. It is hypothesised that the variation observed in response to radiotherapy for prostate cancer patients is arises as a result of inherent differences in the function of key genes. The advent of Next Generation Sequencing of the transcriptome permits the mapping of these changes. This has significant benefits in terms of developing clinically relevant predictors as not only can differences in gene expression levels be detected, mutations within those transcribed sequences and genetic rearrangements can also be detected. One of the most frequently observed genetic re-arrangements (approximately 15-80%) prostate tumours is the TMPRSS2-ERG re-arrangement leading to the induction of ERG expression. The overall objective of this proposal is to investigate whether the presence of this re-arrangement is associated with clinical features of disease including radiation response in prostate cancer patients. Location: School of Medicine and Menzies Institute for Medical Research Antimicrobial drug development Supervisor: Dr Louise Roddam ([email protected]) Note: Honours students undertaking the project are eligible for the Dr Leon Wescombe
Honours Scholarship
(http://www.studentcentre.utas.edu.au/scholarships/AwardDetails.aspx?AwardId=2228) Cystic fibrosis (CF) is an inherited life-shortening condition that results in the build-up of thick and sticky mucus lining the airways that is particularly prone to infection by P. aeruginosa. Despite aggressive antimicrobial therapy this infection, once established, has never been eradicated from the CF lung and is associated with significant lung damage, increased treatment costs, decreased quality of life and increased mortality in people with CF. It is, therefore, clear that new therapeutic strategies are needed to treat these infections. We have developed an antimicrobial therapy that inhibits bacterial quorum sensing, decreases biofilm formation and makes the bacteria more susceptible to conventional antibiotics. Our recent data also demonstrates that this therapy prevents bacterial modulation of human inflammatory pathways and apoptosis and in an acute mouse model prevents bacterial-induced lung inflammation. This project will further explore the safety and efficacy of this therapy using a variety of techniques (bacterial culture, human cell culture, RT-qPCR analysis based on an RNAseq data set, apoptosis assays, DNA damage assays, human cell infection studies, enzymatic activity assays and ELISA).
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Investigation of an emerging pathogen Supervisor: Dr Louise Roddam ([email protected]) Note: Honours students undertaking the project are eligible for the Dr Leon Wescombe
Honours Scholarship
(http://www.studentcentre.utas.edu.au/scholarships/AwardDetails.aspx?AwardId=2228) There is little doubt that the newly described Pandoraea is an emerging multi-drug resistant pathogen capable of establishing chronic lung infections in people with cystic fibrosis (CF) and contributing to lung damage. However, the virulence arsenal and antimicrobial mechanisms used by this organism are yet to be described. We are in a unique position to investigate the pathogenic potential and antibiotic resistance of this organism based on our recent genome and proteome analyses (the first for this human pathogen) using molecular tools available in our laboratory. Additionally, we have developed a new antimicrobial that has yet to be tested against this organism. This project will employ a variety of techniques (bacterial culture, human cell culture, PCR and RT-qPCR, apoptosis assays, DNA damage assays, human cell infection studies, enzymatic activity assays and ELISA). Carbohydrate metabolism in embryonic stem cells Supervisor(s): Dr Joy Rathjen ([email protected]
Associate Professor Nuri Guven ([email protected]) Research Project Synopsis There are many strands of evidence that suggest that nutrients, and specifically amino acids, play regulatory roles in embryonic stem (ES) cells and their differentiation. We have shown that l-proline induces the differentiation of mouse ES cells into a second pluripotent cell population, early primitive ectoderm-like (EPL) cells. In this differentiation process l-proline is taken up by the cell through the system A neutral amino acid transporter, SNAT2, and metabolised by proline dehydrogenase to form reactive oxygen species (ROS) and ∆1-pyrroline-5-carboxylate (P5C). We have shown that pluripotent cells differ in the way l-proline metabolic genes are expressed and we propose that these changes predict the flux of metabolites through the pathway. There is evidence that other pathways could also be differentially regulated in these cells, most prominently the oxidative phosphorylation and glycolytic pathways, and the use of glucose by pluripotent cells. In this project a broad range of techniques will be used to analyse the way naïve and primed ES cells and EPL cells metabolise glucose and to determine if shifts in pathway use occur with lineage development. Specifically, you will use bioinformatics to look at the expression of genes required for each pathway in the cell and find evidence of differential pathway use and potential pathway regulators. Bioinformatic information on gene expression will be validated with qPCR and western blot. You will use standard metabolic assays to determine the fate of glucose in the
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cell, and flow cytometry to determine mitochondrial activity. The results will give us an appreciation of how dynamic carbohydrate use is in the pluripotent lineage. Enhancing neurogenesis to promote recovery following traumatic brain injury Supervisor: Dr Nicole Bye ([email protected]) Brief Project Description: Traumatic brain injury (TBI) is a devastating condition that constitutes a major health and socio-economic burden world-wide. In Australia, hospital admissions for TBI are in the order of 150/100,000 population, with a total lifetime cost per patient estimated at $4.8 million. Many neuroprotective strategies have been employed to try to improve outcome, with little success. Recent research has shown that limited regenerative responses can take place in the adult brain after trauma. One potentially important regenerative process is neurogenesis: the production of new neurons from neural stem/progenitor cells that reside in specific brain regions. While neurogenesis is stimulated after TBI, most of the new neurons die shortly after generation, presumably due to the pathological environment in which they were formed. The brain’s inflammatory response following injury is likely responsible for both stimulating neurogenesis and ultimately killing the new cells. Neuroinflammation involves activation of CNS microglia and astrocytes and infiltration of immune cells, with subsequent expression of numerous cytokines and growth factors. With this project, we will identify cellular and molecular components of neuroinflammation that are responsible for mediating neurogenesis, through treating mice subjected to TBI with anti-inflammatory compounds targeting specific glial populations, or with selected growth factors to augment beneficial inflammatory factors. These studies will also identify whether manipulating inflammation to enhance neurogenesis can promote recovery following TBI. One of the following two topics is to be offered as an Honours research project in 2018 Tuberculosis Supervisor: Dr Ronan O’Toole
[email protected] Tuberculosis (TB) is the leading cause of death in humans worldwide from bacterial infection. In 2015 alone, 10.4 million people developed TB and 1.8 million died from the disease. In the same period, there were in 1,253 new cases of TB in Australia. Deficiencies exist with respect to the clinical tools available for tuberculosis prevention, diagnosis, and treatment. In terms of diagnosis, there is still an over reliance on culture-dependent techniques for both epidemiological typing and drug-susceptibility testing. As the Mycobacterium tuberculosis complex consists of slow-growing mycobacteria, in vitro cultivation remains a primary rate-limiting step in achieving a laboratory-confirmed diagnosis. Accurate and rapid detection of TB are needed for
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informed selection of the appropriate treatment regimen, and minimisation of further transmission of the disease. This project will focus on the use of next generation sequencing to characterise clinical isolates of M. tuberculosis complex and relate mycobacterial genomic variations to the origin and spread of TB disease in patients and the acquisition of drug resistance. Project title: Chronic Obstructive Pulmonary Disease Supervisor: Dr Ronan O’Toole
[email protected] Chronic obstructive pulmonary disease (COPD) is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. It kills over 3 million people worldwide each year according to the World Health Organisation (WHO). It is a major source of hospital admissions in Australia costing the economy an estimated AUD $8.8 billion annually in healthcare expenditure, welfare payments, and lost productivity. Bacterial airway infections worsen the prognosis for COPD patients. At the severe stage of the disease where death may occur, bacterial infection has been implicated in up to 50% of acute exacerbations of COPD, including 72% of those that require ventilatory support. Controlling lung infections is key to improving the survival rate for COPD. Currently, amoxycillin or doxycycline, are recommended for treating COPD acute exacerbations, however, antibiotic use does not reduce hospital stay length or mortality in non-ICU patients. It is also associated with adverse health effects including diarrhoea due to Clostridium difficile infection and the acquisition of drug-resistant strains. This project will focus on the development of a new chemical entity that selectively inhibits infection of the lower respiratory tract by key bacterial drivers of acute exacerbations, Streptococcus pneumoniae and Haemophilus influenzae. Epigenetic machinery and mark alterations in transgenic AD mice Supervisor(s): Dr Adele Woodhouse ([email protected])
Dr Phillippa Taberlay ([email protected]) There is increasing interest in the role of epigenetic changes in Alzheimer’s disease (AD) (Lunnon et al, 2014, Nat Neurosci, De Jager et al, 2014, Nat Neurosci), including post-translational histone modifications (Narayan et al, 2015, Neurobiol Dis; Gjoneska et al, 2015, Nature). These modifications include post-translational modifications of histone proteins that are “written”, “read” and “erased” across DNA by epigenetic modifier complexes such as histone deacetylases (HDACs). Our preliminary data in transgenic AD mice indicate that enhancer (H3K4me1, H3K27Ac) and promoter marks (H3K4me3, H3K27me3) are lost from regulatory regions of key risk factor genes for sporadic AD. Several studies have also shown cognitive benefits of HDAC inhibitor treatment in transgenic AD mice (eg Klein et al, 2015 Neurobiol Aging). However, little is known about the expression of HDACs and histone marks in specific cell types in AD. This project will use immunohistochemistry to determine the global alterations in histone marks and HDACs that occur in AD resistant interneurons and AD susceptible
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pyramidal neurons in 3, 6, 12 and 18 month old AD mice and wild-type controls. Immunohistochemistry will also allow us to assess any changes in the localization of histone marks/HDACs in specific cell types as well as in relation to beta-amyloid plaque pathology. For more information contact Adele Woodhouse Next-generation sequencing to map epigenetic profiles in the brain Supervisor(s): Dr Phillippa Taberlay ([email protected])
Dr Adele Woodhouse ([email protected] Every single cell of the human body contains the same genetic sequence we inherited from our parents; yet, our skin and brain, for example, are remarkably different tissues due to the precision of epigenetic patterning (eg DNA methylation and histone modifications) during development and maintained throughout our lifetime. Our ability to map epigenetic marks across entire genomes occurred only relatively recently, since next-generation sequencing technologies became accessible ~5 years ago. The analysis of ‘big data’ from these studies has created a vast amount of new knowledge about epigenetic patterning, functions and mechanisms; however, these studies have, and are still, largely conducted on samples comprised of multiple cell types (eg whole brain, whole blood). We still have little insight into the depth and breadth of differences between individual cell types. We have developed a method to look at epigenetic marks in specific cell types. This project will use our expertise in DNA methylation (whole-genome bisulphite sequencing), histone modifications (chromatin immunoprecipitation sequencing) and nucleosome occupancy and methylome sequencing to map epigenetic marks in specific cell types from the brain. Viral Immunology Projects
Induction of long-lived antiviral antibody responses by vaccination Supervisor: Associate Professor Guna Karupiah ([email protected]) Natural infection with a number of viruses or vaccination with live viral vaccines provides life-long immunity. Curiously, it is not clear why live viral vaccines induce more robust long-lived antibody responses. Indeed, such information is critical for effective vaccine development strategies. We hypothesized that the increasing concentrations of replicating virus (viral antigens) or vaccines, in contrast to inactivated vaccines, provide important cues to key immune cell subsets for germinal centre (GC) responses. We have found that replication-competent viruses induced significant increases in proportions and numbers of splenic T follicular helper (TFH) cells early in infection, with corresponding decreases in T follicular regulatory cells (TFR), which regulate the GC response. In contrast, the poorly replicating viruses induced only a small rise in TFH numbers whereas TFR numbers remained high. The replicative capacity of virus closely correlated with the magnitude
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of splenic GC B cell and serum neutralizing antibody responses. Similar findings were made with replicating and inactivated strains of influenza A virus. This project will utilize replication-competent and replication-poor recombinant viruses expressing a foreign antigen, in combination with transgenic B cells specific for the foreign antigen, to study antigen-specific B cell responses during viral infection. The focus will be on dendritic cell activation, TFH and TFR and GC B cell responses, induction of somatic hypermutations (SHM), affinity maturation and class switching in antigen-specific B cells. The project will utilise novel recombinant viruses as well as transgenic, mutant and wild type mice to address some fundamental questions in immunology, ie why live viral vaccines or infection with live virus induces much better and durable antibody responses. The project will involve techniques in immunology, virology and molecular biology. This study using mouse models is expected to provide important and relevant insight into design of more effective viral vaccines. Location: School of Medicine Novel approaches to treatment of viral pneumonia Supervisor: Associate Professor Guna Karupiah ([email protected]) Viral infection-induced pneumonia is a consequence of an over-exuberant immune response associated with dysregulated inflammatory cytokine production. There is currently no specific treatment available for this condition, including influenza pneumonia. The available antivirals against influenza A virus (IAV) are effective and reduce inflammation only if treatment is commenced within 48-72 hours of onset of symptoms. We have developed a novel regime for treatment of influenza pneumonia (and one other viral pneumonia) in mice. Our unpublished results indicate that a combination of an antiviral plus a second compound is very effective in reducing viral load, lung pathology and increases the survival rate even if treatment is started late after onset of symptoms. This project will investigate the mechanisms through which the combination therapy overcomes viral pneumonia and will assess the effectiveness of additional compounds. This project will utilize various strains of influenza A virus, wild type, gene knockout and gene knockin mice and will involve techniques in immunology, virology, molecular biology, cell signaling and histopathology techniques. Location: School of Medicine Mechanisms of protection of the host by virus-encoded TNF receptor homolog Supervisor: Associate Professor Guna Karupiah ([email protected]) Tumor necrosis factor (TNF) is a type II transmembrane cytokine (mTNF) expressed on activated cells and cleaved by a metalloproteinase to yield the soluble form (sTNF). Many viruses have evolved strategies to counter the host TNF response, indicating the importance of this cytokine during viral infections.
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Poxviruses encode TNF receptor (vTNFR) homologs of the extracellular domain of mammalian TNFR, which can potentially subvert, dampen or evade the host immune response. Cytokine response modifier D (CrmD) is a vTNFR homolog secreted by ectromelia virus (ECTV), an orthopoxvirus closely related to variola virus (smallpox virus) and a natural mouse pathogen. ECTV causes a disease termed mousepox in mice and is the best small animal model to study poxvirus pathogenesis and immunity to generalised viral infections. Since TNF is critical for recovery of the host from respiratory ECTV infection, we investigated the function of vTNFR using a deletion mutant virus lacking CrmD (ECTVΔcrmD). Whereas the normally resistant wild type (WT) mice recovered from ECTVWT infection, they succumbed to mutant virus infection with severe lung inflammation and immunopathology. This project will investigate the mechanisms through which CrmD protects the host and will utilize novel, genetically engineered mutant viruses and gene knockout/knockin mice involving immunology, virology, molecular biology and cell signaling techniques. The results are expected to have implications on how inflammation during viral infections may be treated, resulting in better health outcomes. Location: School of Medicine Mammalian and viral schlafen proteins: How do they affect the immune system? Supervisor: Associate Professor Guna Karupiah ([email protected]) The schlafen (Slfn) family of proteins has a broad range of activities including growth regulation, differentiation and immunity. Homologs of Slfn genes have been identified in several orthopoxviruses (vSlfn), including camel poxvirus and ectromelia virus (ECTV), both close relatives of the smallpox virus. ECTV is a natural natural mouse pathogen and causes a disease termed mousepox in mice. It is the best small animal model to study poxvirus pathogenesis and immunity to generalised viral infection. We have preliminary evidence that the viral encoded protein modulates host immune response and that the absence of Slfn-2 in mice (mSlfn-2; highest homology to vSlfn) significantly increases the susceptibility of mice that are otherwise resistant to infection with ECTV. This project will investigate the mechanisms through which vSlfn modulates the host immune response and why mSlfn-2 deficiency increases susceptibility of mice to ECTV infection. Some of the questions that will be investigated are (a) how vSlfn modulates the host immune response and what host proteins does it interact with, (b) how mSlfn-2 is involved in the induction of protective immune response against ECTV in the absence or presence of vSlfn, (c) whether genetically engineered ECTV encoding mSlfn-2 can reconstitute the immune defects in mice deficient in mSlfn-2, and (d) whether genetically engineered ECTV encoding mSlfn-1 can reconstitute the immune defects in mice deficient in mSlfn-1. The project will utilise novel, genetically engineered mutant viruses and wild type and mutant mice. It will involve immunology, virology, molecular biology and cell signaling techniques. Location: School of Medicine
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Studying human disease using human brain cells Supervisor(s): Professor David Howells ([email protected])
Dr Brad Sutherland ([email protected]) Dr Emma Eaton ([email protected]) Dr Jo-Maree Courtney ([email protected])
Recent advances in stem cell biology and culture techniques now make it possible to study human cell biology rather than rely on rodent model systems. This capability is likely to increase both the rate of human drug development and our understanding of cell biology in human disease. We are offering Honours projects examining the biology of the cells of the human central nervous system including neurons, glia and pericytes. Understanding how these cells respond to different types of injury, and to candidate drugs, will help identify therapeutic targets for important human diseases such as stroke and dementia. For example, stroke and some forms of dementia are characterised by acute and long-term vascular insufficiency respectively. These trigger a cascade of events that ultimately lead to loss of neural function. We also wish to understand how pericyte contractility is regulated (the key step in regulating blood flow in the brain) and how neurons might be protected against the effects of hypoxia caused by loss of blood flow. Techniques used in the project: Cell culture, cell viability, immunocytochemistry, molecular biology. Please contact the supervisors to discuss the project in more detail. The role of pericytes and vascular function in health and disease Supervisor(s): Dr Brad Sutherland ([email protected])
Professor David Howells ([email protected]) Pericytes are contractile cells that are found exclusively on capillaries throughout the body. In the brain, they are responsible for controlling blood flow as well as maintaining blood-brain barrier (BBB) function and aiding the growth of new blood vessels. Recent research suggests that pericytes may play a key role in outcome after stroke. During an ischaemic stroke, the most common type of stroke, a blood vessel becomes blocked and this starves the affected brain of oxygen and nutrients. A key aim for treating stroke is restoring that blood flow. Recent studies have shown that, after a stroke, pericytes constrict and then die. Because the pericytes die in the constricted state, the capillaries are stuck in their “clamped shut” position and this impedes the restoration of blood flow to the areas of the brain affected by stroke (Hall et al 2014 Nature 508:55-60). The mechanisms that govern these effects in pericytes are currently unknown and uncovering these could provide a novel therapeutic target for stroke. In addition, changes in pericyte function
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within the neurovascular unit could provide insight into other neurological diseases such as Alzheimer’s disease that also have impaired vascular function. Our understanding of pericyte biology within the brain is limited. We offer Honours projects that will use in vivo techniques to determine how pericytes influence blood flow in the brain and maintain the blood-brain barrier. We will use disease models such as stroke or Alzheimer’s disease to uncover the importance of pericytes to the pathophysiology of these conditions. Finally, pericytes are located in the capillary beds of all tissues within the body, and so a comparison between pericytes in the brain and other peripheral tissues will be performed. This research will enhance our understanding of pericytes and determine their roles in the progression of disease, and could potentially give rise to a novel therapeutic target. Techniques used in the project: In vivo models, pathology, molecular biology, behavioural assessment. Please contact the supervisors to discuss the project in more detail. New animal models of human stroke Supervisor(s): Dr Lila Landowski ([email protected])
Dr Brad Sutherland ([email protected]) Professor David Howells ([email protected])
Stroke is a major cause of death and disability. However, our efforts to develop drugs to treat the large numbers of affected people have been compromised by animal models which feature surgical interventions and use of anaesthetics which are not features of the human disease. We offer Honours projects to students interested in helping develop new animal models of stroke which avoid these problems, and evaluation of the fine details of stroke biology that is not usually possible in human patients. Projects are available to examine the detailed cell biology and functional deficits of acute stroke and to examine the long-term consequences of the damage that accrues. These include examination of damage to neurons, glia and the vascular system that supplies the brain with oxygen and nutrients, as well as development of behavioural assays that map the deficits experienced by stroke patients. Techniques: In vivo models, pathology, molecular biology, behavioural assessment. Please contact the supervisors to discuss the project in more detail.
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Division of Paramedicine The following projects are available to students considering undertaking higher degrees by research in 2017. Interested students should contact the primary contact person for the relevant project and arrange to meet and discuss the project. Students should read this document in conjunction with the Research Honours handbook for the School of Medicine, located on the School of Medicine research web page. Any student wishing to discuss honours opportunities not mentioned in the following pages can contact Peter Lucas via [email protected] or on 6226 6952. NOTE: Most of these projects are available to Hobart based students only due to
limited availability of supervisors. Trauma and shock assessment using BSL, SI/MSI and Hb Supervisor(s): Auston Rotheram ([email protected])
Wayne Harris ([email protected]) Research Project Synopsis Australian ambulance services triage trauma patients using tools such as Trauma Score, Injury Severity Score, Perfusion Status Assessment, and Time Critical Guidelines. Large retrospective studies have shown high correlation between Shock Index (Heart Rate:Systolic BP) and mortality and morbidity in patients at arrival in emergency departments. Recently Modified Shock Index (ratio Heart Rate:MAP) has been demonstrated to be even more accurate. Additionally there is evidence suggesting a raise in BSL in adult patients and a drop in BSL in paediatric patients is an indicator of trauma and a drop in haemoglobin in all cases is an indicator for haemorrhage. The proposed study is a retrospective analysis of all trauma cases, across a determined period, involving adult and paediatric patients attended to by Ambulance Tasmania and transported to Burnie Hospital, Royal Hobart Hospital or Launceston Hospital. Key data from these trauma cases will be collected from Ambulance Tasmania’s ePCR data warehouse and from DHHS emergency department on arrival clinical data. The collected data will be used to construct a Shock Index (SI) and Modified Shock Index (MSI) and subsequently analysed to determine the utility these indexes have, as well as Blood Sugar Levels (BSL), in decision making relating to paramedic decisions about treatment and Emergency Department destination choice. Additionally haemoglobin (Hb) will be assessed from emergency department data to ascertain whether point of care testing (PoCT) in the field should be considered. Key findings and recommendations will relate to: • Assessment of SI/MSI, BSL from ambulance cases to the data gathered on arrival at
hospital and relate to injury severity and length of hospital stay.
• Assessment of Hb PoCT as a valid and appropriate tool in trauma cases.
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• Whether paramedics should be using any or all of SI/MSI, BSL and Hb as primary tools in assessing trauma severity.
Student Opportunities Students will have the opportunity to undertake study into projects such as: • The use and documentation of BSL in trauma for adults and its impact on patient
outcome.
• The use and documentation of BSL in trauma for Children and its impact on patient outcome.
• Retrospective construction of a SI/MSI and its impact on patient outcomes.
Use of end tidal CO2 (EtCO2) waveform capnography for evaluation and monitoring in spontaneously ventilating patients Supervisor(s): Wayne Harris ([email protected])
Auston Rotheram ([email protected] Peter Lucas ([email protected]
Research Project Synopsis Waveform capnography is widely available to Australian ambulance services. It provides objective evidence of respiratory patterns and ventilation status, while readily detecting apnoea and respiratory depression, prior to reduction in oxygen saturation. Measurement of EtCO2 in patients with an advanced airway has proven to be an effective, non-invasive indicator of cardiac output during CPR and may be an indicator of ROSC in these patients. Ambulance services routinely assess respiratory and ventilation status in non-intubated patients via subjective methods with varying accuracy. While some Australian ambulance services mandate waveform capnography for intubated patients and throughout subsequent ventilation, there is little use of this technology in monitoring ventilation status in spontaneously breathing patients. The proposed study will consist of a literature review and a retrospective analysis of case records, across a determined period, involving adult and paediatric patients presumed to have respiratory compromise from any cause, presenting to Tasmanian public hospitals. Key data will be collected from these cases via Ambulance Tasmania’s ePCR data warehouse and from DHHS emergency department records. This data will be used to determine the usage of waveform capnography in patients presenting with respiratory compromise to assist in the objective assessment and management of such patients.
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Student opportunities: • Systematic literature review • Involvement in data linkage projects and subsequent analysis • Development of publishable article(s) for peer review • Possibly facilitate change in paramedic practice Paramedic diagnostic accuracy in geriatric patients with complex co-morbidities Supervisor(s): Wayne Harris ([email protected])
Auston Rotheram ([email protected]) Peter Lucas ([email protected])
Research Project Synopsis Geriatric patients pose complex diagnostic challenges. They commonly have atypical presentations of common clinical conditions due to altered physiology, co morbidities and polypharmacy. Geriatric syndromes in particular generate adverse outcomes in this patient group. Paramedics routinely assess and manage geriatric patients with varying accuracy. Assessment tools are available but appear to be sparsely utilised, which may impact diagnostic accuracy and limit index of suspicion regarding severity of the geriatrics’ clinical presentation. The proposed study will consist of a literature review and retrospective analysis of case records, across a determined period, involving geriatric presentations to Tasmanian public hospitals. Key data will be collected from these cases via Ambulance Tasmania’s ePCR data warehouse and from DHHS emergency department records. This data will be used to determine the diagnostic accuracy of paramedic assessment of geriatric patients presenting with acute and/or chronic medical conditions, who also have a recognised geriatric syndrome. Student Opportunities • Systematic literature review.
• Involvement in data linkage projects and subsequent analysis.
• Development of publishable article(s) for peer review.
• Possibly facilitate change in paramedic practice.
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An evaluation of the correct use of paediatric restraint systems for children transported via ambulance Supervisor: Leigh Parker ([email protected]) Research Project Synopsis: Transport of patients in ambulance vehicles throughout Australia is subject to a number of exemptions under the relevant traffic regulations. In the case of transporting children, there is an exemption for the use of restraints such as seat belts and other restraint systems, despite most ambulance vehicles being fitted with or carrying restraint systems for these occupants. Past research conducted by the University of Tasmania indicates that paramedics have a limited understanding of the types and use of a variety of child restraint models and that some paramedics are reluctant to use a child restraint during ambulance transport regardless of the circumstances. This project seeks to further explore the use of child restraints in paramedic practice. Student Opportunities: This project offers several opportunities for Honours students, including: • A chance to further explore the attitudes, beliefs and self-reported practices of
Australasian paramedics towards the use of child restraints in road ambulances.
• A study of how the various types of child restraints influence/do not influence the behaviours of children travelling in a road ambulance.
• A review of how the use of various child restraint systems is taught in Australasian undergraduate paramedic degrees.
• A review of how undergraduates can be taught how to use different types of child restraint, how easily they become proficient and how well they retain their skills
• A chance to explore the expectations of parents whose child is being transported by ambulance
• Comparison of use of paediatric restraints between Australia and the United Kingdom.
An evaluation of the preparedness of Australian ambulance services and/or paramedics to manage mass casualty incidents Supervisor(s): Ms Leigh Parker ([email protected])
Mr Jonathon Sward ([email protected]) Research Project Synopsis: There is an ever-increasing risk of mass casualty incidents (MCIs) both internationally and here in Australia. MCIs may be of natural origin (landslides, earthquakes), or have a degree of human involvement (bombings, train collisions). Irrespective of the cause, MCIs involve multiple injured patients, and often overwhelm the required emergency services’ resources1. Emergency medical services, including ambulance services and
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paramedics, play a key role in the management of MCIs2. As paramedics are likely to attend these incidents, preparedness is a key component of an MCI being managed successfully. Research into ambulance service/paramedic specific MCI preparedness is scarce, especially in Australia. This project will explore the preparedness of ambulance services/paramedics to attend MCIs. This project offers Honours students several opportunities including: • A chance to further explore the preparedness of Australasian paramedics for
attendance at mass casualty incidents
• A study of how the various ambulance services prepare paramedics to manage mass casualty incidents.
• A review of how mass casualty incident preparedness and response strategies are taught in Australasian undergraduate paramedic degrees.
Location: School of Medicine, Hobart. References: 1 Lewis AM, Sordo S, Weireter LJ, Price MA, Cancio L, Jonas RB, et al. Mass Casualty
Incident Management Preparedness: A Survey of the American College of Surgeons Committee on Trauma. The American Surgeon. 2016;82(12):1227-31.
2 Schenk E, Wijetunge G, Mann N, Lerner E, Longthorne A, Dawson D. Epidemiology
of Mass Casualty Incidents in the United States. Prehospital Emergency Care [serial on the Internet]. (2014, July), [cited August 25, 2017]; 18(3): 408-416. Available from: CINAHL with Full Text.
Projects offered by the Allergy and Anaphylaxis Research Group Investigate community and out of hospital management of anaphylaxis to inform best practice guidelines within a multi-disciplinary health care environment Supervisor(s): Dale Edwards ([email protected])
Melanie Blackhall ([email protected]) Research Project Synopsis Currently the first line of community based anaphylaxis treatment is the use of an adrenalin auto-injector device to deliver a lifesaving dose of adrenalin. Current ASCIA best practice guidelines suggest the treatment with adrenalin is the first priority and delaying or withholding adrenalin can result in deterioration and death. The purpose of the project is to investigate management of anaphylaxis in the community and ultimately to provide evidence to support current or future guidelines and clinical practice. This project will explore the incidence of anaphylaxis presentation to ambulance services, and hospital services within Tasmania, the management provided and the
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health outcomes resulting from these presentations. This will allow the research team to determine the frequency and appropriateness of Adrenalin auto injecting device – in general population. There are a number of potential opportunities for honours research within this project including, but not limited to: • Conduct of a retrospective review of presentations to ambulance services,
exploring presentation frequency, management and outcomes.
• Conduct of a retrospective review of presentations to hospital emergency departments, exploring referral pathways, presentation frequency, management and outcomes (including hospital length of stay).
• Review of practice guidelines and protocols for the management of community based anaphylaxis presentations.
By identifying best practice, pre-clinical and clinical teaching practice will be informed across MBBS and paramedic practice degrees. The project will also inform patient education within clinical environment plus preventative health care and clinical protocols. Student Opportunities Students will have the opportunity to undertake one of the above suggested studies, or another variant of study within the field of the Allergy and Anaphylaxis Research Group (AARG). AARG is continually developing new projects and submitting funding grants for further research projects, therefore there are a broad range of opportunities for study. Students should visit the AARG research group page at http://www.utas.edu.au/health/research/groups/allergy-and-anaphylaxis-research-group for further information. Currently underway but may be other possible aspects Understanding hypothermia and hypoxia in unstable newborns born in the out-of-hospital setting Supervisor: Ms Leigh Parker ([email protected]) Research Project Synopsis The management of the newly born infant in an out of hospitals setting includes a sound understanding of the physiological effects of ambient temperature. This project will investigate the paramedic communities understanding of the connection between, and importance of, hypothermia and hypoxia in the infant born in the out-of-hospital environment and subsequently requiring stabilisation. Student Opportunities • The exploration of current paramedic clinical management of the newly born
infant requiring stabilisation.
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• The treatment required or provided in out of hospital birth, including the incidence of such cases.
• The level of documentation recorded, including patient temperature and oxygenation
• The level of equipment and resources available to paramedics in the management of out of hospital childbirth.
Wicking Centre Neuroscience Honours Projects
Honours Projects at the Wicking Centre
1 Wicking Centre Neuroscience Honours Projects 2 Wicking Centre Honours Projects in Care 3 Wicking Centre Honours Projects in Dementia Prevention
Wicking Centre Neuroscience Honours Projects The Wicking Dementia Research and Education Centre has a variety of projects ranging from stem cells and primary culture through to live imaging in the brains of transgenic mice and human cohort studies. A sample of projects are listed here but for more information about potential projects and supervisors within the Wicking group please contact: James Vickers ([email protected]) Anna King ([email protected] Tony Cook ([email protected]) Alison Canty ([email protected]) Matthew Kirkcaldie ([email protected]) Adele Woodhouse ([email protected]) Jenna Ziebell ([email protected]) Bill Bennett ([email protected]) Jacqueline Leung ([email protected]) Duncan Sinclair ([email protected]) Sharn Perry ([email protected]) Honours project in biomarkers of brain health Supervisor(s): Associate Professor Anna King
Professor James Vickers The prevalence of dementia is set to increase substantially throughout the world with the ‘aging’ of the global population and there is an urgent need to develop therapeutic strategies. The most striking change in the brain of a person with dementia is the substantial shrinkage and loss of the brain tissue in affected areas yet the cause of tissue loss is not well understood. It has been documented that neuron loss occurs in most forms of dementia; however, dysfunction and loss of axons and synapses are thought to precede this, resulting in loss of connectivity. Understanding the changes in
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the brain that constitute this tissue loss and detecting these changes in the brains of living individuals, remains one of the biggest hurdles to therapeutic development, particularly in early stages of disease. The overall aim of this project is to try and develop a blood test to tell us about the neurodegenerative changes that are occurring in the brain while a person is still living. Biomarkers are used as surrogate markers of brain changes and are essential in clinical dementia research. Over the last few years there has been progress in the development of blood-based biomarkers in monitoring progression of several of the diseases that cause dementia, as well as traumatic brain injury. While progress has been made in characterizing biomarkers of brain pathology, there has been less advance in characterizing biomarkers of neuron, axon and synapse loss, which constitute “brain health”. This project will examine the decline of neurons, axons and synapses in animal models of dementia and correlate them with key blood based protein biomarkers. This work will be aligned with an examination of blood biomarkers of brain health in a human cohort study. CRISPR/Cas gene editing of human induced pluripotent stem (iPS) cells to investigate childhood-onset neurodegenerative diseases Supervisor(s): Dr Tony Cook
Associate Professor Alex Hewitt Associate Professor Anna King
We utilize CRISPR/Cas technology alongside a boutique collection of patient-specific induced pluripotent stem cell lines to investigate childhood diseases affecting the brain and the eye, including juvenile onset amyotrophic lateral sclerosis, Usher syndrome, and Batten disease. You will generate isogenic iPS cell line using CRISPR/Cas technology, in which the only genetic difference is the presence or absence of a disease-causing mutation. By comparing neurons within cerebral organoids derived from these isogenic iPS lines, you will investigate cellular functions perturbed by these mutations. The results will have major implications for how understanding of the molecular pathways contributing to these diseases, and will provide novel platforms for screening of novel genetic or pharmacological therapeutic targets. Multiple projects are available for 2018, and we are keen to hear from prospective students passionate about using stem cells, genomics or gene editing approaches to develop novel treatment strategies for such diseases. Microglia in neurological diseases Supervisor: Dr Jenna Ziebel Historically, microglia are referred to as the immune cells of the central nervous system, rapidly changing morphology and function when homeostasis is breached. However, evidence is mounting that microglia have many more roles than currently described, including at the synapse. Synapses are the connection of a pre-synaptic neuronal membrane to a post-synaptic neuronal terminal, with support from surrounding glia. As part of “normal” development, synaptic remodelling occurs. This remodelling
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leads to larger circuit reorganisation, changes in synaptic connectivity, and ultimately, brain plasticity. Throughout the normal life-time experience produces multiple, dissociable changes in the brain, including increases in dendritic length, changes in spine density, synapse formation, glial activity, and altered metabolic activity. These synaptic dynamics have been intensely studied, however, synaptic connectivity in relation to microglia has received little attention. This project aims to explore the if modulation of microglia changes their relationship to synapses. A variety of techniques including real-time two-photon imaging as well as more traditional immunohistochemical, protein and RNA analysis will be used to explore the dynamic microglia:sypapse relationship in the adult. By furthering our understanding of these relationships, we will be able to interpret altered microglia:synapse connectivity in experimental model of disease such as Alzheimer’s disease and traumatic brain injury. Developmental maturation of proteins involved in Fragile X Syndrome Supervisor: Dr Duncan Sinclair Fragile X syndrome is a neurodevelopmental disorder which is the leading known genetic cause of autism. Brain abnormalities in Fragile X arise because of loss of the FMRP protein. This project will explore how the proteins involved in FMRP signaling are regulated across the postnatal lifespan in humans, using molecular methods in post-mortem tissue. It will shed light on which developmental epochs are particularly important for key FMRP signaling pathways, and which cell types in the brain are employing these pathways throughout the human lifespan. Using electroencephalography to understand brain circuit abnormalities and sleep disturbances in Alzheimer’s disease model mice Supervisor: Dr Duncan Sinclair Electroencephalography (EEG) is a powerful, non-invasive tool for understanding neural activity which has potential as a biomarker in dementia. This project will use an established mouse model of familial Alzheimer’s disease. It will explore the use of EEG to map emerging pathology in key brain regions across time, and to assess disruptions in sleep quality in response to experimental manipulations in Alzheimer’s disease model mice. Understanding the role of stress hormones in Alzheimer’s disease (2 projects) Supervisor(s): Dr Duncan Sinclair
Dr Tony Cook Professor James Vickers Associate Professor Anna King Dr Sharn Perry
Stress hormone dysregulation is an established feature of Alzheimer’s disease and the target of emerging pharmacotherapies. However, the pathological cycle of stress exposure, cellular pathology and stress hormone dysregulation is not understood. In
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these projects, the behavioural and hormonal responses of Alzheimer’s disease model mice in response to a novel, potentially stressful environment will be investigated across their lifespan. In parallel, cultured neurons from these model mice will be employed to determine the influence of Alzheimer’s disease processes on cellular and molecular stress hormone signaling. Motor function deficits in mouse models of neurodegenerative disease Supervisor: Dr Sharn Perry
The accumulation of neurofibrillary tangles in the frontal and temporal lobes of the brain, caused by the aggregation of proteins, particularly the Tau proteins, is a hallmark feature of neurodegenerative diseases including Alzheimer’s disease and frontotemporal dementia. These tangles cause neural degradation ultimately leading to neural loss, which underlies the progressive cognitive and motor declines associated with dementia. The pathology of tau aggregated proteins is well documented in cognitive circuits that control higher processing such as memory and spatial awareness, however, there is limited knowledge surrounding the pathology and degradation of motor associated circuits and resulting motor behaviour. This project will explore the motor function of a mouse model of Tau pathology using a full repertoire of motor tests across the lifespan of the mouse. In parallel, using a variety of in vivo and in vitro tools, this project will track the disease progression and pathology in motor associated areas, together with the health, functionality and connectivity of neurons within motor circuits. This study will further our understanding of the relationship between the progressive decline in motor neuron functioning and the motor behaviours that manifest throughout the lifespan as a result of Tau pathology. Honours project in axon maintenance Supervisor(s): Associate Professor Anna King
Professor James Vickers The axon is a neuronal structure that is essential for conduction of the action potential. However, few people are aware that the axon can constitute up to 99.9% of the neuronal volume and can transverse through a number of different environments in order to reach its targets. This makes axons incredibly vulnerable in disease and injury. Axons are dynamic structures capable of interacting with their external environment, of rapidly transporting components along their length and of rapid structural plasticity through modulation of their cytoskeleton. Axon can also synthesize proteins and can generate their own self-destruction programme. Our ongoing research programme investigates both the normal functions of axons as well as mechanisms by which axons degenerate in neurodegenerative disease and traumatic brain injury. These projects use a number of innovative techniques including microfluidic compartmented cell culture techniques, live cell imaging both in vitro and in vivo, retinal models of axon degeneration, in vitro and in vivo viral transduction, electron microscopy, neuronal tracing and transgenic animal models of disease and injury as well as standard techniques such as immunohistochemistry, qPCR and Western blot.
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For more information on projects working on axon maintenance contact Anna King [email protected] or James Vickers [email protected] Honours project in Motor Neuron Disease/frontotemporal dementia Supervisor(s): Associate Professor Anna King
Professor James Vickers
Frontotemporal dementia (FTD) and motor neuron disease are neurodegenerative diseases of ageing linked by a common pathological hallmark, the aggregation of a protein called TDP-43. A small number of cases are caused by mutations in the gene encoding TDP-43 however the majority of cases are sporadic or driven by mutations in other genes such as progranulin. This project will investigate the contribution of pathological proteins and conditions to the development of motor neuron disease and frontotemporal dementia. A specific focus of the project will be investigating the mechanisms resulting in loss of connectivity in these diseases. This project will utilize both in vitro and in vivo techniques including cell separation, molecular and biochemical techniques, primary cell culture models, microfluidic technology, viral transduction, live cell imaging and mouse models. You will work amongst a team of researchers and students with expertise in neuroscience research and a focus on dementia. For more information on projects working on FTD contact Anna King [email protected] Wicking Centre Honours Projects in Care Health Services research within the Wicking Centre focusses on care for people living with dementia in different settings. Key areas of interest include optimising care in residential aged care, moving toward dementia friendly communities and enhancing dementia literacy. Opportunities exist to join existing programs of research within these domains and interested individuals are invited to contact Dr Kathleen Doherty or supervisors below. Health student understanding of dementia Supervisor(s): Dr Kathleen Doherty
Dr Claire Eccleston Dr Emma Lea
A key strategy to enable the development of a health workforce capable of providing effective care to people with dementia is the education of health professionals to improve their understanding and skills. Existing research suggests that improved dementia education at an undergraduate level is required to improve students’ capacity to provide evidence-based care for people with dementia, and there is an imperative for undergraduate curricula to incorporate content that addresses the complex care needs of this group. This project will investigate the dementia knowledge of students enrolled in health-related fields at the University of Tasmania, and consider the impact that
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clinical placement programmes may have upon enhancing students' understandings of dementia. Dementia literacy research Supervisor(s): Dr Kathleen Doherty
Professor Fran McInerney Health literacy has been defined as “the skills, knowledge, motivation and capacity of a person to access, understand, appraise and apply information to make effective decisions about health and health care and take appropriate action” (Australian Commission on Safety and Quality in Health Care, 2014). Dementia literacy is a relatively new term and its definition might specifically include the ability to recognise and understand the causes of dementia, sources and utility of information about dementia, knowledge of and access to professional help, and the capacity to take appropriate decisions and actions. The health literacy environment can be seen as “the infrastructure, policies, processes, materials, people and relationships that make up the health system and have an impact on the way that people access, understand, appraise and apply health-related information and services” (ACSQHC, 2014). Important research questions include:
• With respect to dementia literacy: how do current understandings of health literacy resonate in Dementia.
• Do experts and consumers think differently about what dementia literacy means?
• What are the infrastructure, policies, processes, materials, people and relationships that should inform dementia literacy models? Does this differ from other models of health literacy? What are the barriers to consumer access to these?
Improving care for aged care home residents with dementia Supervisor: Dr Emma Lea More than half of the residents in Australian aged care homes have a diagnosis of dementia (Australian Institute of Health and Welfare (AIHW) 2012). People living with dementia have relatively high care needs, which escalate over time, in the domains of daily living and behavioural support. At the end of life, residents with dementia are likely to experience a high symptom burden, akin to cancer, and require skilled palliative care often for months before death. It is vital that care staff in residential aged care homes are skilled appropriately to meet the complexity of the physical, emotional and psychosocial needs of this growing client population. However, despite a desire to deliver the best possible care, care staff rarely have the formal knowledge or capacity to translate evidence into reform of care practices to deliver better outcomes for residents. This project will look at key strategies that can be used to improve care in this setting, using qualitative, quantitative or mixed methods research approaches.
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Wicking Centre Honours Projects in Dementia Prevention It is estimated that addressing modifiable risk factors for dementia could reduce the number of people affected by millions worldwide. The Wicking Dementia Research and Education Centre has developed the Preventing Dementia Massive Open Online Course (MOOC) to educate the community on the latest evidence about dementia risk, and is conducting research to understand community attitudes, motivations and needs. The Centre also has a longitudinal project (Tasmanian Healthy Brain Project) investigating the potential benefits of education in later life. Opportunities exist to join the dementia prevention research program and interested individuals are invited to contact Dr Maree Farrow, [email protected] Relationships between risk factors for Alzheimer’s disease, memory performance and subjective memory complaints Supervisor(s): Dr Maree Farrow
Dr Shannon Klekociuk The Australian National University Alzheimer’s disease risk index (ANU-ADRI; anuadri.anu.edu.au) measures an individual’s risk of developing Alzheimer’s disease, based on known risk and protective factors. Alzheimer’s disease risk may also be predicted by memory performance, but while many older people report memory difficulties, it remains unclear how subjective memory complaints relate to objective performance and the risk of dementia. This project will address whether risk factors for Alzheimer’s disease are associated with objective memory performance and subjective memory complaints, and provide evidence for developing a tool that can effectively assess dementia risk in clinical and community settings. The My INdex of DEmentia Risk (MINDER) Study Supervisor(s): Dr Maree Farrow
Dr Shannon Klekociuk More people are being exposed to dementia; either indirectly through the media, or through affected family members and friends. As a consequence, fear and anxiety related to developing dementia has significantly increased in the community. The term dementia worry has been used to define a construct where individuals experience a higher than normal concern for developing dementia. This project will investigate the relationship between exposure to modifiable dementia risk factors and the extent of dementia worry, and how this relationship might change after exposure to the Preventing Dementia MOOC. Barriers and enablers for brain healthy behaviours Supervisor(s): Dr Maree Farrow
Dr Shannon Klekociuk Participants of the Preventing Dementia MOOC learn about the risk factors for dementia and the potential for dementia risk reduction. This project will examine how they
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intend to apply their new knowledge in their own lives, whether they think it is worth the effort, and what they perceive to be the challenges associated with health behaviour change for themselves and the community as a whole.
Masters of Public Health Research Projects
Understand artificial intelligence and decision support to link laboratory with clinicians and patients Supervisor(s): Dr Kwang Chien Yee ([email protected])
Professor Udayan Ray Dr Ming Chao Wong
Pathology investigations form the essence of modern day medicine, by understanding physiology and pathophysiology. Yet, it is often seen as an isolated discipline that produces results to facilitate clinical care. With the advance of genetics, proteinomics and the availability of these investigations over the internet, the boundaries between pathology, clinicians and patients need to be further defined. Dr Yee, in collaboration with Professor Ray (pathologist) and Dr Wong (health informatics), aims to understand the impact of these changes in pathology services on health services, patient safety and public health. The aim of the research is to assist the application of artificial intelligence and decision support to link laboratory with clinicians and patients. Multiple different projects could be developed in this field, dependent on the candidate’s interests, examples include: • Utilisation of pathology tests for diagnosis, patient’s view
• Patient’s view on online ordering of genetics tests
• Role of responsibility of abnormal results between pathology and clinicians
• Who owns the data on pathology tests? society and medical views
• Utilisation of specific tests for conditions such as FOB, faecal calprotectin etc Interested candidates should read the following publications as the framework: • Yee, KC, “Challenges of the 'omics' future and pathology informatics systems:
are we-pathologists, clinicians, and consumers-ready?”, Archives of Pathology & Laboratory Medicine, 133 (6) pp 938-941. (2009)
• Yee, KC, “An evaluation of clinician's view on electronic pathology reporting
sign off and patient safety”, Studies in Health Technology and Informatics, 188 pp 162-167. (2013)
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Point of care testing of medication adherence: understanding the impact on ethics, socio-technical and patient-doctors relationship Supervisor: Dr Kwang Chien Yee ([email protected]) with national collaborative
team Point of care testing for medication level, such as warfarin level, has been firmly established in the medical practice. This process involves patients and healthcare professionals collaborating to achieve better health outcomes. As technology progresses, point of care testing for other medications will become available in the coming decades. The use of point of care testing technology might change from one of managing medication dosages to one of testing adherence. The use of point of care testing for adherence will face significant challenges from the perspective of ethics, socio-technical interaction and it will have an impact on doctor-patient relationship. User acceptance from both patients and doctors will need to be established. This project aims to understand the ethical, socio-technical and the impact on doctor-patient relationship of point of care testing technologies. The research will utilise mixed methods of interviews and/or survey to understand patient perception, healthcare professional perception and to analysis risks and benefits of such as approach from individuals, healthcare organisation and the community perspective. Social cultural factors influencing the implementation of healthy lifestyle in Tasmania community Supervisor(s): Dr Kwang Chien Yee ([email protected])
Dr Silvana Bettiol Obesity and related diseases are often considered as preventable diseases. Dietary intake and physical exercises are considered as the cornerstone for prevention. Different approaches have been attempted to address this issue, ranging from medical and surgical approach such as laparoscopy gastric banding, to exercise program, dietary program, health literacy program and technology. While all these approaches are important, environmental ergonomics play a significant role. Environmental ergonomics often affect the whole community and raise the issue of inequality of access to factors that will impact of health behaviours, particularly in disadvantage community groups. This broad theme aims to understand and address these factors. Topics might include: • Financial costs of healthy eating in different communities. • Nutritional access for patients in nursing home. • Choice of healthy food for children in restaurants. Interested candidates please contact Dr Yee to discuss further.
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Curing hepatitis C? Exploring socio-cultural factors and understanding long term follow up of patients treated with DAA Supervisor(s): Dr Kwang Chien Yee ([email protected])
Professor Andrew Palmer Dr Barbara de Graaff and others
The availability of new direct anti-viral agent to treat hepatitis C has created new hope that eradication of hepatitis C is possible. New treatment for hepatitis has a success rate of 90% with minimal side effects. The new treatment is costing the government at least A$ 1 billion over the next few years with the view that there are significant health economic benefits in the long run for treatment all patients with hepatitis C. Despite the promising success of virology, there are significant socio-cultural factors that impact on:
• Adherence and success rate. • Real life health economic of various groups of patients with hepatitis C. • Patient’s experience. • Health service delivery model to encourage and engage all at risk patients to
screen for and access treatment. • Socio-cultural factors that impact on patient treatment choices. Difference aspects of these could form honours project, but this project will also be suitable for progression into a PhD. Can we beat liver cancer? Developing a patient-centred liver cancer screening strategy to improve outcomes of liver cancer in Tasmania Supervisor(s): Dr Kwang Chien Yee ([email protected])
Professor Andrew Palmer Dr Barbara de Graaff and others
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is the third leading cause of cancer deaths internationally. The clinical outcomes for patients diagnosed with HCC are highly dependent of when it is detected. Late detection of HCC is associated with significant morbidity and mortality. If detected early, HCC is potentially curable. It has been shown recently that screening detected HCC has a better treatment success and survival rate. Screening programs have been suggested to increase the rate of early diagnosis for at-risk groups. In Australia, screening involves 6-monthly liver ultrasound and alpha-fetoprotein. Current guidelines suggest HCC screening for all patients with cirrhosis, regardless of liver disease severity or aetiology. Several studies internationally have shown that, despite the evidence to support screening for HCC, uptake of screening among at-risk patients is poor.
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The aims of this project are to: a evaluate current uptake and adherence of HCC screening across Tasmania;
b develop strategies aimed at supporting at-risk patients to participate in regular HCC screening; and
c assess the effectiveness of new treatments for hepatitis C in reducing the rate of HCC in Tasmania.
Method: Five studies are proposed for this project. A detailed description of these studies is included on the following page. Briefly, these project are: Study 1: Clinical audit of HCC screening in Tasmania and audit of patients with
hepatocellular carcinoma.
Study 2: The impact of new generation hepatitis C treatments on the development of HCC.
Study 3: Patient survey on uptake of screening, including barriers and enablers.
Study 4: Development of patient-centred disease management strategies/tools.
Study 5: Clinical and health economic evaluation of the disease management strategies/tools.
Outcomes: The overall aim of this project is to increase the rate of early diagnosis of HCC, which will contribute to improved patient outcomes. The specific aims of the Project include: • Establish the current approach to screening for HCC in Tasmania and the current
impact of screening on HCC patients.
• Assess the effectiveness of new hepatitis C drugs in reducing the incidence of hepatitis C in Tasmania.
• Identify factors from a system perspective that impact on poor uptake and adherence to screening.
• Evaluate patient preferences for HCC screening.
• Develop disease management strategies/tools that reflect patient preferences.
• Evaluate the clinical effectiveness of the new disease management strategies/ tools.
• Identify the most cost-effective disease management strategies/tools for Tasmania.
This project is funded. Each study will be able to support an Honours student, with the possibility of extension into PhD project over a few years.
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Pokémon Go and augmented reality games, and the impact on healthcare promotion for obesity related illness Supervisor(s): Dr Kwang Chien Yee ([email protected])
Associate Professor Kate MacIntyre Dr Ming Chao Wong and others
Information and healthcare technology has been used widely with the view of engaging and encouraging the population to participate in behavioral changes which obesity related illness. This has been met with limited success due to message fatigue and the lack of direct association between technology delivered knowledge and behavior. The recent widespread participation of the augmented reality game Pokémon Go which appears to encourage exercises as socialization provides significant insights into the potential role of augmented reality games in health behavior. The rapid uptake of Pokémon Go by the population around the world, however, should serve as a useful lesson for information and technological design to improve outcomes obesity-related diseases in the future. Our research has investigated the potential conceptual model of how augmented reality game could improve patient uptake of healthy behavior. We have also examined features and factors that will encourage health behavior. The next step in our research is to measure outcomes associated with using augmented reality games in improving health behaviors. Candidates interested in Pokémon Go and augmented reality games in improving healthcare outcomes should read the following two published articles as a background introduction to discuss projects. • Wong MC, Turner P, MacIntyre K, Yee KC. Pokémon-Go: Why Augmented Reality
Games Offer Insights for Enhancing Public Health Interventions on Obesity-Related Diseases. Stud Health Technol Inform. 2017; 241:128-133.
• Yee KC, Wong MC, Turner P. Pokémon Go: Ubiquitous Computing Delivering Better Health or Co-Incidental Health Benefits from Technology Use? A Participatory Observational Study. Stud Health Technol Inform. 2017;234:389-394.
Using anticipatory care and big data analytics to predict, design and transform future healthcare delivery Supervisor(s): Dr Kwang Chien Yee ([email protected])
Associate Professor Kate MacIntyre and others Big data analytics has been touted as the next big healthcare innovation that will transformed the future of healthcare systems. Many commercial social media platforms are already performing big data analyatics to inform consumer behaviours.
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While big data analytics might well have possibility of transforming healthcare system, the fundamental promise of big data analytics is that we can anticipate and predict care requirement and therefore design healthcare delivery of the future. This step needs a lot more research work, especially in Tasmania. This project aims to combine anticipatory care principles and big data analytics to understand how data could improve quality and safety of patient care in the future. Potential candidates must contact the supervisor to discuss the area of interest, so that we could work on a project that will allow development of big data analytics and anticipatory care principles in that area.
