C A N C E R | I M M U N E D I S O R D E R S | I N F E C T I O U S D I S E A S E

Head of Structural BiologyWALTER AND ELIZA HALL INSTITUTE

Information for prospective candidates

1603

31

2 | Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates

OUR MISSIONMastery of disease through discovery

OUR VISIONTo be an innovative medical research Institute that enriches society through discovery and education and improves health outcomes through translation

OUR VALUES

● Pursuit of excellence ● Integrity and mutual respect ● Collaboration and teamwork ● Creativity ● Accountability ● Contribution to society

OUR STRATEGIC GOALSStrategic goals of the Walter and Eliza Hall Institute of Medical Research Strategic Plan (2015 – 2020) are:1. make discoveries that shape contemporary

scientific thinking, increase understanding and improve prevention, diagnosis and treatment of cancer, immune disorders and infectious diseases;

2. educate and train the next generation of world class scientists and attract, develop and retain the best and brightest workforce;

3. provide a vibrant and inspiring organisational culture that encourages, promotes and rewards excellence, creativity, mutual respect and collaboration;

4. engage with our stakeholders to improve scientific outcomes, build support and secure resources for the Institute and medical research; and

5. build infrastructure, professional services and funding

INSTITUTE AT A GLANCE2015

931staff and students

130institute and visiting speakers

5516people came to an event at the institute

40+diseases impacted by institute research

381publications

100national and international trialsbased on institute discoveries

1000staff and students

931staff and students

130institute and visiting speakers

5516people came to an event at the institute

40+diseases impacted by institute research

381publications

100national and international trialsbased on institute discoveries

40+diseases impacted by Institute research

931staff and students

130institute and visiting speakers

5516people came to an event at the institute

40+diseases impacted by institute research

381publications

100national and international trialsbased on institute discoveries

100national and international trials based on Institute discoveries

86publications with impact factor >10 410publications

37Patents granted in 2015

Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates | 3

ABOUT THE INSTITUTEThe Walter and Eliza Hall Institute is Australia’s oldest medical research institute. It was founded in 1915 with financial support from a trust established by Eliza Hall, following the death of her husband Walter. The vision was for an institute that ‘will be the birthplace of discoveries rendering signal service to mankind in the prevention and removal of disease and the mitigation of suffering’.Throughout the Institute’s history its researchers have focused on understanding the fundamental principles of medical biology and using this knowledge to mitigate disease.Our current researchers and students continue to work on solving basic science questions through curiosity-driven research. We are committed to innovative science that expands and improves our understanding of basic human biology and the disruptions to systems that cause disease. Our scientists also undertake blue-sky research that creates and explores new areas of biology.Three nationally and globally significant areas of health have been long-term, central interests of our research:

• cancer – understanding the basic processes that are disrupted to generate cancer cells and how these can be targeted to treat disease;

• immunology – discovering how the body fights infection, and how errors in the immune system lead to disease; and

• infectious diseases – today with a focus on globally significant pathogens, especially malaria and chronic infections.

We take a multidisciplinary approach to addressing major research questions, integrating expertise in bioinformatics, clinical translation, genomics, medicinal chemistry, personalised medicine, proteomics, structural biology and systems biology.The Institute offers postgraduate training as the Department of Medical Biology of The University of Melbourne, and is affiliated with The University of Melbourne and The Royal Melbourne Hospital. The Institute also has strong ties with many research organsations in Melbourne and around the world.

INSTITUTE LEADERSHIPDirector - Professor Douglas J Hilton ao

BSc Mon BSc(Hons) PhD Melb FAA FTSE FAHMS

Deputy Director/Scientific Strategy - Professor Alan CowmanBSc(Hons) Griffith PhD Melb FAA

Deputy Director/Science Integrity and Ethics - Professor David VauxBMedSci MBBS PhD Melb FAA FAHMS

Deputy Director/Strategy and Operations - Ms Samantha LudolfBA(Hons) Lincoln MEnterp Melb

Institute Board President - Mr Chris Thomas BCom (Hons) MBA Melb FAICD

HEALTH IMPACTSThe Institute is committed to making fundamental scientific discoveries that can be translated to better treatments, bringing real benefits to the community on a global scale. Clinical trials based on discoveries made at the Institute include trials of vaccines for coeliac disease, diabetes and malaria; and trials of a new class of anti-cancer drugs, called BH3-mimetics, for treating people with leukaemia and other cancers.

CANCERBowel cancerBrain cancerBreast cancerLeukaemiaLung cancerLymphomaMelanomaMyelomaMyeloproliferative diseaseOvarian cancerPancreatic cancerProstate cancer Stomach cancer

IMMUNE DISORDERSAllergy AsthmaCoeliac diseaseInflammatory bowel diseaseLupusMultiple sclerosisPsoriasisRheumatic fever and rheumatic heart diseaseRheumatoid arthritisSepsisType 1 and type 2 diabetes

INFECTIOUS DISEASEFilariasis Hepatitis BHIVLeishmaniaMalariaScabiesToxoplasmosisTuberculosis

4 | Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates

STRUCTURAL BIOLOGY DIVISION – BACKGROUND AND ACHIEVEMENTS Since its establishment in 2001, the Walter and Eliza Hall Institute’s Structural Biology division has been a leading site for the analysis of proteins important for both therapeutic development and for the progression of structural biology for its own sake.

The founding head of the division, Professor Peter Colman, brought with him a wealth of international structural biology and biotechnology experience and success. Professor Colman’s determination of the three-dimensional structure of influenza virus neuraminidase formed the basis for the world’s first anti-influenza drugs, which were developed by Biota Pharmaceuticals Inc. and Glaxo, who brought Relenza™ to the market. Professor Colman’s success was built on his broad collaborations, access to the best equipment and his fostering of talented researchers.

At the Walter and Eliza Hall Institute, Professor Colman has recruited and mentored scientists with interests in the insulin receptor, the epidermal growth factor receptor (EGFR), cytokine signalling, apoptosis and medicinal chemistry. Under his leadership the division has grown from fewer than ten scientists and students to almost 100 researchers. The division was so successful that the medicinal chemistry expertise was able to form part of a new division at the Institute, the ACRF Chemical Biology division. The Structural Biology division currently has eight laboratory heads leading forty staff and students. Major collaborations have been established in cell surface biology, receptor and cytokine signalling and programmed cell death.

Many world-first discoveries have been made by the division, including the first structures of the extracellular domain of the EGFR with its ligand, the full-length human gp130 cytokine receptor, insulin in complex with a portion of the extracellular domain of the insulin receptor, the extracellular domain of erbB2 , a SOCS3-JAK signalling complex, the activated pro-apoptotic Bcl-2 family proteins and the structures of T-cell signalling complexes and stem cell markers such as Lrig1. The division was also the site of the first structure of a potassium channel to be determined in Australia. These projects are empowered by collaborations with internationally successful scientists in other Walter and Eliza Hall Institute divisions, and more broadly with biologists across the globe.

As well as supporting the establishment of the crystallography beamlines at the Australian Synchrotron, the division has been a premier site for the application of other state-of-the-art structural biology techniques including high-field NMR, microcalorimetry and biosensor analysis. Where new technologies have emerged, such as cryoelectron microscopy, the division has established connections to international sites and has championed the development of shared facilities in Australia.

A major element in the success of the Structural Biology division is the enthusiasm of collaborating biologists within the Institute, and the overall environment of the Institute. Structural information produced by the division is used by biology colleagues at the Institute to improve understanding of disease processes, by Institute medicinal chemistry colleagues to develop drugs directed to the target structures and by Institute clinical colleagues working with Melbourne Health and the Victorian Comprehensive Cancer Centre to have the drugs tested in the clinic. For example, the division’s structural studies on the EGFR led to the discovery of the mechanism of action of a “tumour-specific” antibody, mAb806. This discovery encouraged the pharmaceutical development of the antibody, which has already benefited brain tumour patients. Another major success is the structure-based medicinal chemistry program of pro-apoptotic drugs which target Bcl-2 family proteins. Collaboration between the Institute’s medicinal chemists, clinical colleagues and the pharmaceutical industry (AbbVie and Genentech, a member of the Roche group) has led to a new pro-apoptotic drug (venetoclax) that has now been validated and approved for clinical use for people with certain forms of chronic lymphocytic leukaemia.

Cell surface receptors remain a major challenge for structural biologists and the division has had considerable success in obtaining high-resolution structures for growth factor and cytokine receptors as well for as stem cell markers and enabled direct structure-function analysis of ion channels. Recent successes in analysing the insulin / insulin receptor complex has led to structure-based design of agonists, with exciting possibilities for improved drugs for the treatment of diabetes.

It is an exciting time for structural biology at the Walter and Eliza Hall Institute and the new division head will find the position poised to make significant discoveries that will be of benefit both to biology and medicine.

Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates | 5

STRUCTURAL BIOLOGY DIVISION - PUBLICATION HIGHLIGHTS• Babon JJ, Kershaw NJ, Murphy JM, Varghese LN, Laktyushin A, Young SN, Lucet IS,

Norton RS, Nicola NA. Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity. Immunity. 2012 Feb 24;36(2):239-50. PMID: 22342841.

• Clarke OB, Caputo AT, Hill AP, Vandenberg JI, Smith BJ, Gulbis JM. Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels. Cell. 2010 Jun 11;141(6):1018-29. PMID: 20564790.

• Czabotar PE, Westphal D, Dewson G, Ma S, Hockings C, Fairlie WD, Lee EF, Yao S, Robin AY, Smith BJ, Huang DC, Kluck RM, Adams JM, Colman PM. Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell. 2013 Jan 31;152(3):519-31. PMID: 23374347.

• Garrett TP, McKern NM, Lou M, Elleman TC, Adams TE, Lovrecz GO, Kofler M, Jorissen RN, Nice EC, Burgess AW, Ward CW. The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol Cell. 2003 Feb;11(2):495-505. PMID: 12620236.

• Kershaw NJ, Church NL, Griffin MD, Luo CS, Adams TE, Burgess AW. Notch ligand delta-like1: X-ray crystal structure and binding affinity. Biochem J. 2015 May 15;468(1):159-66. PMID: 25715738.

• Kershaw NJ, Murphy JM, Liau NP, Varghese LN, Laktyushin A, Whitlock EL, Lucet IS, Nicola NA, Babon JJ. SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition. Nat Struct Mol Biol. 2013 Apr;20(4):469-76. PMID: 23454976.

• Knoblich K, Park S, Lutfi M, van ‘t Hag L, Conn CE, Seabrook SA, Newman J, Czabotar PE, Im W, Call ME, Call MJ. Transmembrane Complexes of DAP12 Crystallized in Lipid Membranes Provide Insights into Control of Oligomerization in Immunoreceptor Assembly. Cell Rep. 2015 May 26;11(8):1184-92. PMID: 25981043.

• Lessene G, Czabotar PE, Sleebs BE, Zobel K, Lowes KN, Adams JM, Baell JB, Colman PM, Deshayes K, Fairbrother WJ, Flygare JA, Gibbons P, Kersten WJ, Kulasegaram S, Moss RM, Parisot JP, Smith BJ, Street IP, Yang H, Huang DC, Watson KG. Structure-guided design of a selective BCL-X(L) inhibitor. Nat Chem Biol. 2013 Jun;9(6):390-7. PMID: 23603658.

• Menting JG, Whittaker J, Margetts MB, Whittaker LJ, Kong GK, Smith BJ, Watson CJ, Zakova L, Kletvikova E, Jiracek J, Chan SJ, Steiner DF, Dodson GG, Brzozowski AM, Weiss MA, Ward CW, Lawrence MC. How insulin engages its primary binding site on the insulin receptor. Nature. 2013 Jan 10;493(7431):241-5. PMID: 23302862.

• Menting JG, Yang Y, Chan SJ, Phillips NB, Smith BJ, Whittaker J, Wickramasinghe NP, Whittaker LJ, Pandyarajan V, Wan ZL, Yadav SP, Carroll JM, Strokes N, Roberts CT, Jr., Ismail-Beigi F, Milewski W, Steiner DF, Chauhan VS, Ward CW, Weiss MA, Lawrence MC. Protective hinge in insulin opens to enable its receptor engagement. Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3395-404. PMID: 25092300.

• Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI, Young SN, Varghese LN, Tannahill GM, Hatchell EC, Majewski IJ, Okamoto T, Dobson RC, Hilton DJ, Babon JJ, Nicola NA, Strasser A, Silke J, Alexander WS. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity. 2013 Sep 19;39(3):443-53. PMID: 24012422.

• Trenker R, Call ME, Call MJ. Crystal Structure of the Glycophorin A Transmembrane Dimer in Lipidic Cubic Phase. J Am Chem Soc. 2015 Dec 23;137(50):15676-9. PMID: 26642914.

• Webb CT, Gorman MA, Lazarou M, Ryan MT, Gulbis JM. Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller. Mol Cell. 2006 Jan 6;21(1):123-33. PMID: 16387659.

6 | Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates

ABOUT THE STRUCTURAL BIOLOGY DIVISIONThe Structural Biology division is interested in discovering new medicines through studies of the three-dimensional structure of large biological molecules that are either targets for drugs or potential therapeutic agents in their own right. The division currently houses 7 laboratories with a total of 32 staff and 13 students.

Work of the division has a health impact in the following areas: cancers (including bowel cancer, brain cancer, leukaemia, lymphoma, myeloma, myeloproliferative disorders); immune disorders (type 1 and type 2 diabetes); infectious disease (malaria); and other areas (heart disease and stroke, neurodegenerative disease).

KEY SELECTION CRITERIADesirable knowledge and skills include

• Potential to perform at the level of NHMRC Principal Research Fellow or Senior Principal Research Fellow

• Record of highly original research contributions

• Exposure as an international authority

• Strategic management ability and success in gaining research funds

Personal qualities

• Outstanding interpersonal and communication skills with capacity to further develop linkages

• Adherence to the highest standard of integrity and of scientific practice and the presence to be an effective model in this regard

• A generosity of spirit that recognises and encourages the achievements of other scientists

• An individual who leads by enthusiasm, energy and maturity and who will be deeply committed to broader to the Institute and broader goals

Leadership

• Leadership and capacity to foster excellence

• Strong strategic planning, decision making, results focus and organisational skills and the resultant capacity to lead and manage a division in an ever changing environment

• A leadership style that promotes a co-operative culture throughout the division and that allows collaboration with the Institute within the Institute and wider community

Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates | 7

KEY ACCOUNTABILITIESThe Division Head’s key responsibilities that are desirable but not essential include:

Scientific Direction & Performance

• Advise on, plan and coordinate research direction

• Proactively contribute to the Institute’s strategic direction, formulation and implementation of the strategic plan

• Encourage creativity, innovation and originality

• Review and improve research performance in an ongoing manner

• Advise on the preparation of research proposals, and funding applications

• Represent the Institute at conferences, serve on expert committees, and participate nationally and internationally as appropriate to the discipline

People Management

• Inform, involve, and lead staff

• Identify and nurture potential in all staff

• Develop and manage performance of Laboratory Heads and other direct staff

• Plan staffing requirements for the Division

• Proactively encourage work life balance and a family friendly work place

Financial

• Identify potential funding sources and gain major peer reviewed grants for the Division

• With support from a finance business partner:-

- Define the proposed resource requirements for the Division over the period of the Institute Strategic Plan including technological and computational requirements.

- Endorse proposed laboratory budgets

- Oversee the financial management of the laboratory expenditures against budget and take appropriate action

Resource Management

• Allocate laboratory and other space to Laboratory Heads within negotiated Divisional allocations

• Contribute to design and planning of new facilities and improvements

…continued over

8 | Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates

Commercial Relations

• Monitor Division research for potential commercialisation (recognising the importance of open-source software in the bioinformatics and statistics communities)

• Encourage scientific entrepreneurship

• Establish processes to ensure review public disclosures for potential intellectual property protection prior to presentation and publication by Division staff

• Ensure inventor takes out patent protection as appropriate

• Contribute to commercial relations policy and procedures development and implementation

Standards & Regulatory Compliance

• Oversee compliance with regulatory, ethical, and professional standards within Division

• Monitor the recording and retention of research activities and results• Monitor Laboratory Head compliance with regulatory and funding agency

requirements and ethical standards

Health, Safety & Environment

• Monitor the health and safety performance of the Division• Contribute to establishing health and safety policies and standards for the

Institute• Oversee the establishment of health and safety programs, processes and

structures• Monitor compliance with safety policies, standards, legislation, procedures and

good practice• Participate in appropriate health and safety committees and programs• Recommend and implement health and safety improvements• Set a good example

Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates | 9

STRUCTURE AND GOVERNANCEThe Walter and Eliza Hall Institute is incorporated in Victoria as a company limited by guarantee. It has no shareholders and monies received and generated are invested in the activities of the Institute. The Institute has charitable status with the Australian Taxation Office as a deductible gift recipient.

The business of the Institute is governed by the board which is responsible for oversight of the policies, strategic direction and management of the Institute. In turn, the board delegates to the Institute director (who is the chief executive officer) the overall responsibility for the scientific program and management of the Institute. Board members are drawn from business, the professions and academia.

The Walter and Eliza Hall Institute is affiliated with The Royal Melbourne Hospital (Melbourne Health) and The University of Melbourne. These affiliations are reflected in the board membership where both organisations have nominees. A further indication of this affiliation is that the director of the Institute is also Professor of Medical Biology at The University of Melbourne.

The director and the board are supported and advised by a network of board committees, advisory committees and faculty and management committees.

INSTITUTE STRUCTUREThe Institute’s 850 research staff are assigned to theme-based research divisions, but collaboration across the Institute is fostered and encouraged. Researchers are supported by more than 100 professional services staff.

ACRF Chemical Biology division Headed by Professor Benjamin Kile and Associate Professor Guillaume Lessene

ACRF Stem Cells and Cancer division Headed by Professor Geoff Lindeman and Professor Jane Visvader

Bioinformatics division Headed by Professor Gordon Smyth

Cancer and Haematology division Headed by Professor Warren Alexander and Professor Nick Nicola

Cell Signalling and Cell Death division Headed by Professor John Silke and Professor David Vaux

Development and Cancer division Headed by Associate Professor Anne Voss

Immunology division Headed by Professor Phil Hodgkin

Infection and Immunity division Headed by Professor Alan Cowman and Professor Marc Pellegrini

Inflammation division Headed by Professor Ian Wicks

Molecular Genetics of Cancer division Headed by Professor Jerry Adams and Professor Andreas Strasser

Molecular Immunology division Headed by Professor Stephen Nutt

Molecular Medicine division Headed by Professor Doug Hilton

Population Health and Immunity division Headed by Associate Professor Melanie Bahlo and Professor Ivo Mueller

Structural Biology division Currently headed by Professor Peter Colman (retiring)

Systems Biology and Personalised Medicine division Headed by Professor Liam O’Connor

10 | Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates

INSTITUTE ORGANISATION STRUCTURE

FundraisingMs Susanne Williamson

Deputy Director/ Strategy and Operations

Ms Samantha Ludolf

Scientific StrategyDeputy Director/

Science Integrityand Ethics

Director Professor Doug Hilton

Chief Information OfficerMr Michael Carolan

Procurement andLogistics ManagerMr Todd Jasper

Chief Financial OfficerMr Ian Coulson

Laboratory Operations and Scientific Services ManagerDr Helene Martin

Head, Business DevelopmentDr Julian Clark

Head, People and CultureMs Fran Boyd

Acting Head, Communicationsand MarketingMs Merrin Fabre

Grants ManagerDr Julie Mercer

Internal AuditorMr Stan Balbata

Facilities ManagerMr Steve Droste

Management and Committee Structure

General CounselMs Gabrielle Hirsch

Planning ManagerMs Catherine Parker

Library Services and Research Support ManagerMs Wendy Hertan

Research divisions &Clinical TranslationBioinformaticsProfessor Gordon Smyth Cancer and HaematologyProfessor Warren Alexander Professor Nick NicolaCell Signalling and Cell DeathProfessor John SilkeProfessor David VauxACRF Chemical BiologyProfessor Benjamin KileA/Professor Guillaume LesseneDevelopment and CancerA/Professor Anne Voss ImmunologyProfessor Phil HodgkinInfection and ImmunityProfessor Alan CowmanProfessor Marc Pellegrini InflammationProfessor Ian WicksMolecular Genetics of CancerProfessor Jerry Adams Professor Andreas StrasserMolecular ImmunologyProfessor Stephen NuttMolecular MedicineProfessor Doug Hilton Population Health and ImmunityProfessor Melanie BahloProfessor Ivo MuellerACRF Stem Cells and CancerProfessor Geoff LindemanProfessor Jane Visvader Structural BiologyProfessor Peter Colman Systems Biology and Personalised MedicineProfessor Liam O’ConnorClinical TranslationProfessor Andrew RobertsComputational Biology CentreA/Professor Tony Papenfuss

Professor David VauxProfessor Alan Cowman

Deputy Director/

Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates | 11

FINANCIAL STATEMENTS OVERVIEW 2015

Business development2%

Building operation6%

Support laboratories18%

Fundraising1%

Centenary program1%

Administration6%

The period in brief ($ ‘000s)

2015

6 months to 31 December 2014

Income for operations 103,706 55,467

Expenditure in operations 105,438 53,547

Net surplus (deficit) from operations (1,732) 1,920

Number of staff and visiting scientists 662 692

Number of postgraduate students 169 159

Total staff and students (EFT)s 831 851

Other income11%

Philanthropic Grants, Fellowships – Australia

8%

Victorian Government 7%

Australian Government 47%

Scientific laboratories 66%

Investment income13%

Philanthropic Grants, Fellowships - Overseas

7%

Donations and bequests 7%

Income

Expenditure

12 | Head of Structural Biology, Walter and Eliza Hall Institute – Information for prospective candidates

TERMS OF APPOINTMENT

CONTACT DETAILS

The division head is appointed by the Institute for a period of five years, renewable and is accountable to the director.

EXPRESSIONS OF INTEREST

Expressions of interest, which should address the key selection criteria and include a comprehensive curriculum vitae, should be sent to Ms Yvonne Sirinotis, People and Culture Advisor at jobapplications@wehi.edu.au, quoting reference WEHI/YSSB

Professor Douglas J Hilton

Director Walter and Eliza Hall Institute of Medical Research 1G Royal Parade Parkville VIC 3052 Australia

Telephone: +61 3 9345 2552 Email: hilton@wehi.edu.au