Annual Report 2010-2011

Mastery of disease through discovery | www.wehi.edu.au Contents

1 About the institute 3 Director’s and Chairman’s report 5 Discovery 8 Cancer and Haematology 10 Stem Cells and Cancer 12 Molecular Genetics of Cancer 14 Chemical Biology 16 Molecular Medicine 18 Structural Biology 20 Bioinformatics 22 Infection and Immunity 24 Immunology The Walter and Eliza Hall Institute 26 Autoimmunity and Transplantation of Medical Research 28 Cell Signalling and Cell Death 1G Royal Parade 30 Inflammation Parkville Victoria 3052 Australia Telephone: (+61 3) 9345 2555 32 Molecular Immunology Facsimile: (+61 3) 9347 0852 34 Publications WEHI Biotechnology Centre 36 Awards 4 Research Avenue 37 Translation La Trobe R&D Park Bundoora Victoria 3086 Australia Translating our research 38 Telephone: (+61 3) 9345 2200 40 Developing our research Facsimile: (+61 3) 9345 2211 42 Patents www.wehi.edu.au www.facebook.com/WEHIresearch 43 Education www.twitter.com/WEHI_research 46 2010-11 graduates ABN 12 004 251 423 47 Seminars Acknowledgements 48 Institute awards Produced by the institute’s Community Relations department 49 Engagement Managing editor: Penny Fannin Editor: Liz Williams 51 Strategic partners Writers: Liz Williams, Vanessa Solomon and Julie Tester 52 Scientific and medical community Design and production: Simon Taplin Photography: Czesia Markiewicz and Cameron Wells 54 Public engagement 57 Engagement with schools Cover image 58 Donor and bequestor engagement Art in Science finalist 2010 Vessel webs 59 Sustainability Dr Leigh Coultas, Cancer and Haematology division 60 The Board This image shows the delicate intricacy in the developing eye of a transient population of web-like blood vessels. The cells in 64 General Manager’s report the vessels will be depleted during development in a regulated 66 Building our future process called apoptosis, or programmed cell death. Tumours frequently recruit and develop extensive blood 68 Institute organisation supplies to help them grow. Scientists from our Cancer and Haematology division are investigating ways of killing tumours 69 Members of the institute by inducing apoptosis. The mechanisms that cause apoptosis in 70 Supporters and donors the cells pictured may be useful in understanding how we can induce apoptosis in tumour blood vessels, effectively killing 74 Financial year at a glance cancer cells by starving them of their blood supply. About the institute

Our mission Mastery of disease through discovery

Our vision To be an innovative medical research institute that engages and enriches society and improves health outcomes through discovery, translation and education.

Research themes

CANCER | CHRONIC INFLAMMATORY DISEASE | INFECTIOUS DISEASE

Key objectives

Discovery to make discoveries in medical biology that shape contemporary thinking and paradigms and enhance the understanding and treatment of disease

Translation to convert our discoveries into improvements in disease diagnosis, prevention and treatment

Education to develop and enrich the skills and experience of students and staff, allowing each person to realise their potential and contribute to a vibrant campus

Engagement to engage with the community and develop support for medical research generally and the institute’s mission specifically An interior view of the new western Sustainability to build an infrastructure, funding and research wing of the institute (below left) capacity that enables the institute to fulfil its mission and an exterior view of the front in a sustainable manner of the building (below right).

Annual Report 2010-2011 Walter and Eliza Hall Institute 1 The Walter and Eliza Hall Institute is home to more than 650 Director researchers who are working to understand, prevent and treat Douglas J Hilton diseases including cancer – particularly blood cancers and breast BSc Mon BSc(Hons) PhD Melb FAA cancer; chronic inflammatory diseases such as type 1 diabetes, Deputy Director rheumatoid arthritis and coeliac disease; and infectious diseases such as hepatitis and malaria. David Vaux MB BS BMedSc PhD Melb FAA It is committed to making fundamental discoveries about the way cells, particularly cancer and blood cells, behave and General Manager communicate and seeing these discoveries translated into Maureen O’Keefe BSc(Hons) Mon DipEd MBA Melb benefits for patients. GAICD WCLP The institute was founded in 1915 as a benevolence of the Walter Company Secretary and Eliza Hall Trust to be ‘the birthplace of discoveries rendering signal service to mankind in the prevention and removal of Murray Jeffs BBus(Accounting) RMIT disease and the mitigation of suffering’. CPA FCIS SF Fin It is affiliated with The University of Melbourne and The Royal Honorary Governor and Patron Melbourne Hospital. It offers postgraduate training as the Sir Gustav Nossal AC CBE Department of Medical Biology of The University of Melbourne. MB BS BSc(Med) Syd PhD Melb HonLLD Mon HonLLD Melb HonMD Mainz HonMD Ncl HonMD Leeds HonMD UWA HonDSc Syd HonDSc Qld HonDSc ANU HonDSc UNSW HonDSc LaT HonDSc McMaster HonDSc Oxon FRCP FRACP FRCPA FRACOG(Hon) FRCPath FRACGP FRSE FTSE FAA FRS

Dr Matthew Call and Dr Melissa Call (below left) jointly manage a laboratory in the Structural Biology division. Dr Thomas Nebl (below right) has recently joined the institute’s Systems Biology and Personalised Medicine division.

2 Walter and Eliza Hall Institute Annual Report 2010-2011 Director’s and Chairman’s report

Although we are only part-way through our building and renovation program, which is due to be completed in November 2012, the past 12 months have seen some major milestones being met, most notably the completion of the new western wing of the building and the relocation of many of our researchers into this state-of-the-art facility. Two aspects of this project have been particularly pleasing. First, we have been able to deliver this part of the project on time and under budget, and hence have been able to commit to fully renovating the east wing of our building. Second, occupation of the building proceeded exceptionally smoothly, with our scientists performing experiments within days of moving. We look forward to the completion of this project and the building’s formal opening in 2012, and thank the Australian and Victorian Governments, The Atlantic Philanthropies, The Ian Potter Foundation, the Australian Cancer Research Foundation, the Drakensberg Trust and numerous other donors and supporters for supporting this major project. The institute’s centenary in 2015 is rapidly approaching, giving us the opportunity to reflect on our history and our current position. Eliza Hall’s vision for the institute was that it should “be the birthplace of discoveries rendering signal service to mankind in the prevention and removal of disease and the mitigation of suffering”. Our researchers have made Mrs Hall’s vision a reality: from Sir Charles Kellaway’s production of anti-venom in the 1930s, to Sir Macfarlane Burnet’s Nobel Prize-winning theory of clonal selection in the 1950s, and Professor Don Metcalf’s discovery of colony stimulating factors in the 1960s, which not only revolutionised Institute director Professor haematology, but over the past 20 years has helped more than 10 million cancer Doug Hilton (below left) with patients complete their chemotherapy with reduced risk of infection. board president Mr Leon Davis

Annual Report 2010-2011 Walter and Eliza Hall Institute 3 In the past 12 months we have added to proteins that give cancer cells a survival radio, television and online. We are also this legacy. advantage. This means that cancer immensely proud of the role played by our Our scientists have made many patients at The Royal Melbourne Hospital animators, Mr Drew Berry and Ms Etsuko fundamental discoveries, including the are among the first in the world to benefit Uno, who take complex biomedical ideas visualisation of the malaria parasite in from these new designer therapies. and turn them into highly informative, ‘super resolution’; elucidating the role that The first of these new compounds, accessible and beautiful animations. Their the major human cancer-causing gene navitoclax, is now in phase II clinical work has been downloaded from YouTube ERG plays in stem cell self-renewal; the trials, while the second, ABT-199, which hundreds of thousands of times; displayed demonstration that parasitic worms use was co-developed by chemists and in art galleries and museums, including the same family of cell survival proteins structural biologists at the institute, is in the Museum of Modern Art in New York; as human cancer cells; and that the blood phase Ia trials in patients with chronic received a British Academy of Film and cell hormone interleukin-7 can boost the lymphocytic leukaemia who have not Television Arts award and this year was response to human viral pathogens such responded to conventional treatment. recognised by a Macarthur Fellowship as HIV, hepatitis B and hepatitis C, which Equally exciting are the three different (also known as the Genius Award) to are major health burden globally. vaccine approaches that have emerged Mr Berry. On the translational side there is from our research efforts into malaria Funding and donations have again also much excitement and anticipation. over the past 20 years, which are now played a major role in supporting the Australian cancer patients are benefiting in clinical trials in humans, as well as work of our institute. We are truly from the 20 years of effort invested by the ongoing clinical development of grateful for support we have received more than 100 institute scientists in preventive approaches for diabetes and from governments and donors this year. unravelling the mysteries of cell death coeliac disease. It has made all our work possible and and cell survival. This collaboration has If new treatments and new technologies allowed us to develop young talent which involved molecular and cell biologists, are going to have maximum impact will underwrite our future research. medicinal chemists, structural biologists, on disease prevention, diagnosis and We have no doubt that when future clinicians and nurses – in short, the treatment, the Australian community leaders and supporters of the institute full spectrum of research talent at the must embrace health and medical reflect on this period, that they will recall institute and in our precinct partners. research. We have been overwhelmed a halcyon time. We thank you for being Because of our deep understanding of this by the support we have received from part of the Walter and Eliza Hall Institute area of biology, two major international the community, not only during the family and trust you will take much pharmaceutical companies, Abbott and ‘Discoveries Need Dollars’ campaign that pride in the achievements of our staff Genentech, a member of the Roche group, preceded the federal budget in May, but and students. have chosen to collaborate with us to help also in response to stories about our work develop pharmaceuticals which target that have appeared in the print media,

Remembering Frank Fenner 21.12.1914 – 22.11.2010

Last year, institute staff mourned the loss of Antibodies, a key publication in about a subject and imparting that to of one of the great minds of Australian immunology that outlines Burnet’s as wide an audience as he could. He science, acclaimed virologist and seminal ideas about ‘self’ and ‘non-self’ in was an inspiration for generations of microbiologist Professor Frank Fenner. the immune system. scientists and epitomised the dedicated Professor Fenner was best known for Professor Fenner’s work at the humanitarian academic.” his work in eradicating smallpox and for institute cemented his interest and his studies of the myxomatosis virus, used involvement in virology, particularly to control rabbit plagues from the 1950s. poxviruses, which were to be his lasting For a short but influential time in legacy and contribution to science and the late 1940s, Professor Fenner worked human health. at the Walter and Eliza Hall Institute. Professor Phil Hodgkin, head of Professor Fenner was recruited by then immunology at the institute, worked director Sir Macfarlane Burnet to work with Professor Fenner at the John Curtin on Ectromelia, or mousepox as they later School of Medical Research during the called it. 1980s and 1990s. Professor Fenner and Sir Macfarlane He remembers Professor Fenner as Burnet showed that mice could be an “incredibly generous scientist”. “We vaccinated against mousepox with always felt very privileged to be in his vaccinia virus, another poxvirus company, to hear his stories and to be historically used to vaccinate humans guided by his wisdom and experience,” against smallpox. They remained close Professor Hodgkin said. “He just friends, and co-authored The Production loved finding out everything he could Professor Frank Fenner

4 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

PhD student Ms Sarah Best, from the Stem Cells and Cancer division, is seeking to better understand the role of particular proteins in mammary gland development.

Annual Report 2010-2011 Walter and Eliza Hall Institute 5 Discovery

Collaborative and multidisciplinary research has long been a strength of the Walter and Eliza Hall Institute. Although our research groups are clustered in divisions to reflect common interests, research collaborations span divisions and many of our most important discoveries have been the outcome of cross-disciplinary, cooperative efforts. Our researchers are united towards improving human health, focusing on cancer, chronic inflammatory disease and infectious diseases. As part of the institute’s expansion, which began in early 2009, a reorganisation of the research divisions has been undertaken to better reflect the core research interests of our scientists and the institute’s strategy. This resulted in the formation of three new divisions in 2011 – Cell Signalling and Cell Death, Inflammation, and Molecular Immunology. In addition, the division of Stem Cells and Cancer was established in 2010, and a new division of Systems Biology and Personalised Medicine will begin in July 2011. As part of the reorganisation, the division of Autoimmunity and Transplantation ceased operations in December 2010, with the reassignment of researchers to allied divisions. Contemporary biology requires researchers to integrate data from diverse fields, including genomic, proteomic, cell-based and statistical analyses. The institute PhD student Ms Sweta Iyer (below supports the ongoing research activities of our scientists by providing access to left) is investigating how the proteins Bak and Bax insert into advanced technologies and by promoting collaboration between specialists in the mitochondrial membrane, distinct fields, and encouraging researchers to develop skills in diverse areas. As leading to programmed cell death. the following pages demonstrate, our successes in the past year have stemmed from Dr Nai Yang Fu (below right) is a strong collaborative, cross-divisional approach that sees our research discoveries looking for the genes that may span from basic science to translational research. be behind some breast cancers.

6 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Understanding the role of the Bcl-2 family in health and disease It is more than 20 years since institute and Genentech, a member of the Roche Our scientists also remain committed to researchers identified the role of the Group. The entry of ABT-199 into clinical basic research into the biology of the Bcl-2 Bcl-2 protein family in preventing trials highlights the institute’s ability to family. Research from the Immunology, the death of leukaemia cells, and the translate basic discoveries into potential Inflammation, Molecular Genetics of subsequent discovery of the role of Bcl-2 new therapies for human disease. Cancer and Molecular Immunology in programmed cell death. Since then, The Bcl-2 family is also important divisions has defined which Bcl-2-like the combined efforts of our researchers in other diseases. Scientists in our proteins are required for the development have resulted in important discoveries Autoimmunity and Transplantation, Stem and maintenance of specific T and B cell about the function of Bcl-2 and related Cells and Cancer, and Bioinformatics subsets. Scientists in the Cell Signalling molecules and their relevance to health divisions have revealed the potential and Cell Death division are elucidating and disease. In 2011 this resulted in for inhibitors of Bcl-2 family members how some Bcl-2-like proteins function the start of phase Ia clinical trials of a to be used to treat rheumatoid arthritis to initiate cell death. Another important potential new BH3-mimetic inhibitor and breast cancer. Research from the advance has been the determination, of Bcl-2, called ABT-199 (GDC-0199/ Molecular Genetics of Cancer, and Cancer by researchers in the Structural Biology RG7601), for the treatment of chronic and Haematology divisions has shown division, of the crystal structures of lymphocytic leukaemia, the most the importance of Bcl-2-like proteins Bcl-2-like molecules bound to natural common type of leukaemia. ABT-199 was in the formation of blood vessels that and pharmacological inhibitors. This discovered and developed through a three- supply nutrients to solid tumours. These information will be especially important way collaboration between scientists in are all exciting developments that have for advancing the design of new inhibitors the institute’s Chemical Biology division the potential to be developed into new of Bcl-2 family members, which could lead and pharmaceutical companies Abbott treatments for these diseases. to new potential therapies for cancer.

New ways to treat infectious diseases Improving treatments for infectious chronic infectious diseases in humans Plasmodium parasite by scientists in diseases has been a focus of the institute including HIV and hepatitis B and C, the Infection and Immunity division since its founding. In 2010-2011 which are significant disease burdens in continues to reveal potential new drug our scientists have made important developing nations. targets for treating malaria. Major discoveries that have revealed new Parasitic diseases are another focus achievements in this field in the past year strategies for combating viral and for our scientists. Research from the have included the discovery of a new parasitic diseases. Structural Biology and Bioinformatics family of proteins required by the parasite Scientists in the Infection and divisions has revealed that the parasite to recognise red blood cells, and, for the Immunity division have demonstrated that causes schistosomiasis expresses first time, the visualisation of the parasite that the cell signalling molecule Bcl-2-like molecules. This raises the invasion process in molecular detail. This interleukin-7 (IL-7) has the potential possibility that modulation of the information is being used by researchers to boost the immune response to fight Bcl-2 family may be a novel option for in the Chemical Biology division to persistent viral infections in mice. treating parasitic diseases. Research discover new antimalarial compounds in This opens up new avenues for treating into the biology of the malaria-causing a high-throughput chemical screen.

Silencing the immune response to treat disease Chronic inflammatory diseases such as coeliac disease through desensitisation to type 1 diabetes and rheumatoid arthritis proteins in gluten. put immense strain on health systems Institute scientists have also advanced the worldwide. Our researchers have made understanding of the cellular and molecular significant advances in determining how mechanisms that drive inflammation. The to diminish the immune response as a Inflammation division is investigating the means of treating or preventing these role of secreted molecules in controlling diseases. Scientists in the Autoimmunity inflammatory cells. Meanwhile, scientists and Transplantation, and Immunology in the Molecular Immunology division divisions have developed vaccines that are have defined a subset of white blood currently in clinical trials. An intranasal cells that are important for suppressing vaccine has been developed for preventing the immune response. These discoveries type 1 diabetes by stimulating tolerance could lead to new strategies to combat to insulin, while another vaccine inflammatory diseases in the future. HIV researchers Dr Marc Pellegrini currently being trialled aims to cure (above left) and Mr Simon Preston

Annual Report 2010-2011 Walter and Eliza Hall Institute 7 Cancer and Haematology

Leukaemias and autoimmune disorders develop when the mechanisms controlling normal blood cell proliferation and function are subverted. The Cancer and Haematology division aims to discover the molecules that control these regulatory processes with the ultimate goal of devising new strategies for fighting disease. We work collaboratively with other institute divisions, particularly Molecular Medicine and Inflammation, and have strong links with clinical and commercial partners for research translation. Our researchers use rapidly-evolving genomics tools to discover novel regulators of blood cell production and function. Recent discoveries in this area have highlighted the important role and intricate regulation of blood stem cells, the rare bone marrow cells responsible for lifelong blood cell production, which often develop disease- Laboratory heads causing mutations. Our studies of the c-Myb and Erg transcription factors have Professor Warren Alexander revealed novel mechanisms via which stem cells sense and respond to the number Division head of mature blood cells, as well as how stem cell functions are differentially controlled Dr Jeff Babon under normal and stress conditions. Originally discovered in our division, the blood cell hormones (cytokines) control Dr Emma Josefsson the number and function of blood cells, and have been used to treat patients with Dr Benjamin Kile low white blood cell numbers, which often result from cancer therapy. To improve Dr Graham Lieschke treatment, as well as design new therapies for inflammation and cancers, we continue to explore the mechanisms of cytokine action. Recent research highlights include Professor Donald Metcalf the discovery by Dr Jeff Babon of a novel biochemical mechanism by which the Dr Matthew McCormack Suppressors of Cytokine Signalling (SOCS) proteins switch off cellular responses to Professor Nick Nicola cytokines, which has important implications for the design of inhibitors of cytokine Division head action (see opposite page). Dr Samir Taoudi We also welcomed the appointment of new laboratory heads whose skills and research Professor Andrew Roberts activities enrich and extend the division’s program. Dr Emma Josefsson, who studies regulation of platelet production and function, will continue this research theme and explore the roles of platelets in cancer. Dr Matthew McCormack brings an exciting Dr Jeff Babon (below left) program of research into leukaemia-causing genes and leukaemia stem cells, and Dr and Professor Nick Nicola are studying the interactions Samir Taoudi, appointed jointly with the Molecular Medicine division, whose research of internal cell signalling is unlocking the mysteries of how the blood cell system develops. proteins called Janus kinases.

8 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Cell signalling discovery provides new hope for treating blood disorders

Myeloproliferative diseases are serious type are produced, and the bone marrow He said the finding could inspire a new blood disorders that cause an excessive is overrun, leading to problems with class of therapeutic agents for treating number of blood cells to accumulate in production of other essential cell types myeloproliferative diseases. “The SOCS3 the bone marrow. They can be severe and eventually bone marrow failure,” binding site is a previously unknown part and are sometimes fatal. he said. of JAK2 which could be exploited as a Dr Jeff Babon, Professor Nick Nicola Dr Babon investigates the interaction drug target, with greater specificity than and colleagues from the institute’s between JAK2 and the inhibitory SOCS other drugs that are currently in clinical Structural Biology and Cancer and (Suppressors of Cytokine Signalling) trials for inhibiting JAK2,” he said. Haematology divisions have spent proteins. SOCS were discovered at the many years studying the interactions of institute in the 1990s and provide a Collaborating organisations: internal cell signalling proteins called necessary ‘negative feedback’ response Monash University and The University Janus kinases (JAKs). JAKs are activated that stops JAK2 becoming overactive. of Melbourne. in response to blood cell hormones “SOCS3 is a key inhibitor of JAK2 called cytokines and are essential for proteins in blood and immune cells, Funding partners: National Health maintaining the blood system and for but we didn’t know exactly how the and Medical Research Council, National instructing immune cells to respond to two proteins interacted to suppress Institutes of Health (US), and the infection and inflammation. JAK2 function,” Dr Babon said. “In our Victorian Government. Dr Babon said mutations in one research, we were interested in identifying particular molecule, JAK2, are strongly which site the SOCS3 protein bound to on More information: Presented at the associated with the development of the JAK2 protein to inhibit its action. We 39th Annual Scientific Meeting of the myeloproliferative diseases. “When were surprised to find that SOCS3 binds Society for Hematology and Stem Cells, JAK2 is mutated, it tells the cell to to a unique site on JAK2, and directly Melbourne, 15-18 September 2010. continually multiply, or proliferate. An inhibits the protein, rather than out- excessive amount of blood cells of one competing other molecules.”

Advancing medical research through better microscopes

Microscopy is a vital tool in medical who is studying the control of cell death research, and recent advances in in the blood vessel lining. technology have provided scientists with “In this case, we need to see the entire new and more detailed views into cells sample to be able to accurately count and tissues. the number of blood vessels in it,” he A donation of almost $25,000 by The said. “We are using this information to Jack Brockhoff Foundation has allowed determine the role of different genes in institute researchers to capitalise on these blood vessel cell death. This research advances by enabling an upgrade of our may provide clues for killing tumour- Zeiss LSM 5 Live microscope. associated blood vessels, thereby starving The upgrade means institute the tumour of its blood supply.” microscope users can now create highly- The head of the institute’s Imaging detailed images of whole organs, using Facility, Dr Kelly Rogers, said the up to four separate fluorescent markers. upgraded microscope would benefit Dr Leigh Coultas from the Cancer many research projects. “There is high and Haematology division used the demand for fluorescent microscopy microscope to produce the image on the from our scientists,” she said. “As well cover of this annual report: a blood vessel as the studies of blood vessel regulation, network in the developing eye. the upgraded microscope has been Dr Leigh Coultas produced the “Often, it is only by visualising an used to gain insights into how malaria extraordinary image on the cover of this year’s annual report with the institute’s entire sample in high resolution that we parasites invade red blood cells, and how upgraded microscope. The microscope can get an accurate picture of what is autoimmunity develops.” upgrade was made possible by a donation happening in biology,” said Dr Coultas, from The Jack Brockhoff Foundation.

Annual Report 2010-2011 Walter and Eliza Hall Institute 9 Stem Cells and Cancer

The Stem Cells and Cancer division studies the normal development of epithelial tissues and organs, and cancers arising within them. Epithelial organs are those that primarily consist of epithelial cells – such as skin, breast, ovary and lung. Cancers of epithelial cells (carcinomas) account for approximately 80 per cent of cancers and are major causes of death and disease worldwide, yet improved treatment strategies have only resulted in modest improvements in cancer survival. Our division is focusing on breast, ovarian and lung cancers, with the key objective of understanding the normal development of these organs and which cell types within them are predisposed to cancer. In the breast cancer laboratory we have made significant inroads into identifying the different types of epithelial cells that reside in breast tissue. Recent studies have revealed that breast stem cells are highly responsive to the hormones oestrogen and progesterone, despite lacking receptors for these hormones. Our laboratory unravelled the cellular mechanism that accounts for the link between sustained exposure to female hormones and increased breast cancer risk. We identified, through gene expression profiles, which genes in epithelial cells are affected by hormone actions, including the RANK signalling pathway. Current work is addressing whether blocking this pathway Laboratory heads can prevent breast cells becoming cancerous, or inhibit tumour growth. We are also investigating genes that regulate mammary gland development in order Dr Marie-Liesse Asselin-Labat to understand how changes to these genes could contribute to cancer development. Professor Geoff Lindeman Analysis of different mouse models of breast cancer and human breast tissue has Division head revealed potential ‘cells of origin’ of cancer. We are also undertaking studies that have Associate Professor Clare Scott the potential to identify molecules that could serve as novel prognostic markers or Professor Jane Visvader therapeutic targets in breast cancer. Division head Similar approaches are being applied to studying ovarian and lung cancers. Ovarian cancer usually presents at a late clinical stage and is often resistant to existing therapies. The most lethal type is high-grade serous ovarian cancer. To better understand this Professors Jane Visvader (below left) and Geoff Lindeman aggressive form of cancer we are generating preclinical models of disease to test new believe that BH3-mimetics treatments. Studies in the lung cancer laboratory are also centred on establishing a could hold promise for treating bank of lung cancer models representative of different cancer subtypes. aggressive breast cancers.

10 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Anti-cancer agents show promise for aggressive breast cancers

Triple negative breast cancers account chemotherapy drugs, and prevent the “The research suggests that these for up to 20 per cent of all breast cancers cancer cells from dying. BH3-mimetic agents make the cancer and are typically aggressive with a The BH3-mimetic compound ABT-737 cells more vulnerable to chemotherapy,” poor prognosis. targets proteins from the Bcl-2 family, Professor Visvader said. “We are They are called triple negative which are found at high levels in up to particularly excited about using this cancers because they test negative for 70 per cent of breast cancers, Professor combination to treat Bcl-2-expressing the oestrogen, progesterone and HER2 Lindeman said. “We have shown that breast cancer, including basal-like receptors, and cannot be treated with breast tumours that have high levels of breast cancer, which is often the hardest hormone therapy or drugs that have Bcl-2 respond well to treatment with to treat.” been useful in treating other forms of ABT-737 when used in combination with a breast cancer. conventional chemotherapy drug,” he said. Funding partners: Australian Cancer Researchers from the institute have Professor Visvader said combined Research Foundation, National Breast found that some of the most aggressive treatment with ABT-737 and docetaxel Cancer Foundation, National Health and forms of breast cancer are more (a chemotherapy drug commonly Medical Research Council, Victorian Breast vulnerable to chemotherapy when the used for treating breast cancer) in Cancer Research Consortium, Victorian chemotherapy is combined with a new mice transplanted with human breast Cancer Agency, Victorian Cancer Biobank, class of anti-cancer agent. cancer cells improved tumour response and the Victorian Government. Professors Geoff Lindeman and Jane and survival rates, when compared to Visvader, who led the research with docetaxel as a single agent. More information: Oakes SR, Vaillant colleagues Drs Samantha Oakes and Professor Lindeman said early results F, Lim E, Lee L, Breslin K, Feleppa F, François Vaillant, said that a new class of suggest navitoclax (an orally-deliverable Deb S, Ritchie ME, Takano E, Ward T, anti-cancer agents called BH3-mimetics BH3-mimetic which is an analogue of ABT- Fox SB, Generali D, Smyth GK, Strasser showed promise for treating breast 737) could provide new hope for treating A, Huang DC, Visvader JE, Lindeman cancers, including triple negative cancers. some breast cancers that are not candidates GJ. Sensitization of BCL-2-expressing BH3-mimetics target and neutralise for other currently available treatments. breast tumors to chemotherapy by the the so-called Bcl-2 proteins in cancer Navitoclax is being jointly developed by BH3 mimetic ABT-737. Proceedings of the cells. Bcl-2 proteins act to ‘protect’ the pharmaceutical companies Abbott and National Academy of Sciences USA. 2011 cells after they have been damaged by Genentech, a member of the Roche Group. Jul 18; doi: 10.1073/pnas.1104778108

L’Oréal Fellowship winner seeks to understand cancer

A desire to understand how breast In 2011 Dr Asselin-Labat established cancer starts saw institute researcher her own laboratory in the Stem Cells Dr Marie-Liesse Asselin-Labat win one and Cancer division, focusing on lung of three 2010 L’Oréal Australia For cancer. “I’m interested in looking at how Women in Science Fellowships. lung stem cells are regulated and what The L’Oréal Fellowships are awarded drives tumour initiation in the lungs,” to female early career scientists to reward Dr Asselin-Labat said. research excellence and support their rise “Our laboratory intends to use the to leadership positions in science. discoveries into breast stem cells and Dr Asselin-Labat from the institute’s their role in breast cancer to further Stem Cells and Cancer division received our understanding of how lung cancer the $20,000 L’Oréal Fellowship for develops. There is a real need for research her research into breast stem cells into lung cancer, because remarkably little and their role in some types of breast is known about how it develops and the cancer. She was part of the institute cells that are at the origin of the cancer.” team that identified breast stem cells, a Dr Asselin-Labat said the L’Oréal discovery that caused a major shift in Fellowship had allowed her to get the way scientists thought breast cancer laboratory assistance to maintain developed. The team also revealed that productivity, helped with childcare oestrogen and other female hormones can costs, and supported her participation in control the function of breast stem cells. leadership training. Dr Marie-Liesse Asselin-Labat

Annual Report 2010-2011 Walter and Eliza Hall Institute 11 Molecular Genetics of Cancer

Normal cells in our bodies have a limited lifespan and those that are damaged, potentially dangerous, or no longer needed are eliminated by a process of programmed cell death called apoptosis. A cell that develops a defect in its apoptosis machinery will fail to die when it should and may multiply to give rise to cancer. Further, defective apoptosis makes cancer cells resistant to the chemotherapy and radiation interventions commonly used to treat cancer. Our division is exploring how apoptosis is controlled and how disruptions in this vital cellular process lead to cancer and limit the effectiveness of current therapies. Importantly, our increased understanding of apoptosis has galvanised the search for novel drugs that directly trigger the apoptotic machinery to kill cancer cells. One of the two distinct pathways to apoptosis is triggered when ‘death receptors’ Laboratory heads on the cell surface are engaged by protein ligands that bind specifically to these receptors. The other pathway is triggered when various stress stimuli produce Professor Jerry Adams Division head signals inside the cell that act upon the Bcl-2 protein family; the resulting tussle between opposing factions of this family determines whether the cell lives or Dr Philippe Bouillet dies. The process is controlled by three forces: Bcl-2 and the other pro-survival Professor Suzanne Cory family members restrain their pro-death relatives Bak and Bax until the apoptosis- Dr Ruth Kluck initiating ‘BH3-only’ proteins issue the death warrant. Thus, the death receptors Associate Professor Clare Scott and the Bcl-2 family represent separate molecular switches controlling apoptosis. One promising new approach to cancer therapy attempts to cut off the tumour’s Professor Andreas Strasser Division head blood supply by damaging growing blood vessels within the tumour. This year, we showed that in such therapies the BH3-only protein Bim drives destruction of tumour blood vessels, starving the tumour cells of vital nutrients (see opposite PhD student Mr Colin page). In separate studies, we showed that Bim and Mcl-1 are key players in drug Hockings (below left) resistance. Bim was found to enhance the effect of DNA-damaging chemotherapies PhD student Ms Natasha Anstee in lymphomas, while pro-survival protein Mcl-1 impeded cell death after (below right) has received a scholarship from the Leukaemia radiation damage. These discoveries have important implications for predicting Foundation for her research into the effectiveness of treatment strategies for tumours in which these proteins are the pro-survival protein Mcl-1 switched on. in acute myeloid leukaemia.

12 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

New strategy to attack tumour-feeding blood vessels

The growth of solid tumours, such mimetics that cause cell death by acting Funding partners: Cancer Council as lung cancers, breast cancers and like Bim at a molecular level. Victoria, National Health and Medical melanomas depends on nutrients and “A promising new approach to Research Council, Australian Research oxygen from the blood. treating solid tumours may be to use a Council, National Institutes of Health (US), Cancer cells encourage the growth three-medication combination of a drug The Leukemia & Lymphoma Society (US), of blood vessels to feed a tumour that specifically targets the tumour, Genentech, a member of the Roche Group, by producing the hormone-like an anti-angiogenic agent to impair the and the Victorian Government. protein vascular endothelial growth tumour blood vessels, and a BH3-mimetic factor (VEGF). that will help the anti-tumour drug to More information: Naik E, O’Reilly Scientists from the institute’s Molecular directly kill tumour cells and also will LA, Asselin-Labat ML, Merino D, Lin A, Genetics of Cancer, and Cancer and help the anti-angiogenic agent to starve Cook M, Coultas L, Bouillet P, Adams Haematology divisions have discovered the tumour of nutrients,” Professor JM, Strasser A. Destruction of tumor a key molecule needed to kill the blood Strasser said. vasculature and abated tumor growth vessels that supply tumours. Professor upon VEGF blockade is driven by

Andreas Strasser led the research, which Blood proapoptotic protein Bim in endothelial showed that tumour-produced VEGF supply cells. Journal of Experimental Medicine. blocked production of Bim in the cells 2011 Jul 4; 208(7):1351-8. that line the tumour blood vessels. The research team found that if anti- cancer therapies that target tumour blood vessels are to work, the death-inducing Tumour molecule Bim is required. The finding could lead to improved anti-cancer The diagram shows how BH3-mimetic treatments that are based on a two- or BH3-mimetics can act on Blood vessel three-pronged attack on both the tumour tumour cells (purple) and newly developing blood and its blood supply. vessel cells (brown), in Professor Strasser said that strategies combination with anti- for treating tumours by attacking the cancer and anti-angiogenic Anti-cancer tumour blood supply could be optimised therapies, to aid in the VEGF therapy treatment of cancer. Anti-angiogenic by incorporating agents called BH3- therapy

Investing in finding leukaemia treatments

Leukaemia is the eighth most common postgraduate studies. She will study the models that have been developed at cancer in Australia, and more than 4800 role of pro-survival protein Mcl-1 in acute the institute.” people will be diagnosed with leukaemia myeloid leukaemia (AML). Ms Anstee said that, despite progress this year. AMLs often express high levels of being made over the past several decades The Leukaemia Foundation has been Mcl-1 and this is associated with a in treating AML, there is a need to a strong supporter of the Walter and poor response to treatment and a poor develop new therapies for the disease. Eliza Hall Institute’s quest to find new prognosis. Ms Anstee will be testing “AML is one of the most common treatments for leukaemia. The foundation the response of leukaemias that over- forms of acute leukaemia, and despite has partnered with the institute to express Mcl-1 to conventional and recent advances, AML still has a poor support talented young scientists for the new treatments. prognosis, with only 23 per cent of past six years, supporting 11 institute “Several pharmaceutical companies patients surviving five years after scientists studying various aspects of are currently directing a lot of effort diagnosis. We hope that this research will blood cancer, particularly understanding towards developing Mcl-1-specific drugs, contribute to the development of new, how disturbances in the cell death with a view to improving treatment for more targeted therapies that will improve pathway are linked to cancers. AML and other tumours expressing high the survival rate in AML patients.” This year, PhD student Ms Natasha levels of Mcl-1,” said Miss Anstee. “I will Anstee received a $120,000 grant from the be comparing the efficacy of such drugs Leukaemia Foundation to undertake her with that of existing drugs in laboratory

Annual Report 2010-2011 Walter and Eliza Hall Institute 13 Chemical Biology

The Chemical Biology division focuses on developing and applying state-of-the-art chemical approaches for studying important biological and medical problems, to ultimately develop novel and improved therapeutics. A major research focus is cancer, particularly the role of impaired cell death in driving and maintaining tumours. One abnormality that is prominent in some types of blood cancer is overactivity of the protein Bcl-2, which acts to inhibit cell death. Our longstanding collaborations with other institute scientists have helped clarify how Bcl-2 normally functions and importantly, how it might be targeted for treating cancer. A three-way collaboration between the institute and pharmaceutical companies Genentech, a member of the Roche Group, and Abbott has led to the development of a compound called ABT-199 (GDC-0199/RG7601) that targets Bcl-2, currently in phase Ia clinical trials for patients with leukaemia. We are continuing to investigate how cell survival is controlled, as clarifying Laboratory heads this regulatory process may allow us to design and develop strategies to block Associate Professor Jonathan Baell or promote cell death. There are also active programs pursuing other cancer targets, such as key enzymes that promote tumour formation. In this regard, Dr Chris Burns the division has strong links with the Cancer Therapeutics CRC. Professor David Huang Some of the novel therapeutic agents being investigated are also likely to be Division head useful for diseases such as autoimmunity and inflammation. In collaboration Dr Guillaume Lessene with colleagues from the Infection and Immunity division, we are working Dr Ian Street on new treatments for malaria. An essential part of our drug discovery infrastructure is the institute’s high-throughput chemical screening (HTCS) facility, which enables identification of chemical compounds that have PhD student Ms Silvia Teguh (below left) properties suitable for their development into drugs. Dr Brad Sleebs (below Our research brings together the fundamental disciplines of chemistry and right) is looking for ways biology, and applies them to identifying, characterising and targeting molecules to improve existing drugs so we can develop better treatments for diseases such as cancer and malaria. through chemistry.

14 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Designing new treatments for cancer through chemistry

Developing chemical compounds as Medicinal Chemistry in which they and optimise their activity, providing drugs for treating disease is often a described creating a re-engineered us with a strong platform for developing lengthy process, requiring a detailed compound that could kill cancer cells by better anti-cancer drugs.” analysis of their properties and how they binding specific Bcl-2-like proteins. interact with the body. “The compound is called an ‘isostere’, Collaborating organisations: Institute researchers are looking to meaning it has significantly different Genentech, a member of the Roche group, develop new and better drugs for treating chemical properties to the original and Abbott. diseases such as cancers and malaria. As compound while retaining comparable Funding partners: The Leukemia & part of this search, they are looking for biological activities,” Dr Sleebs said. Lymphoma Society (US), National Health ways to improve existing drugs, such as “The compound we created is an and Medical Research Council, Cancer by modifying their chemical structures to isostere of an existing anti-Bcl-2 Council Victoria, Australian Cancer improve safety, biological activity, chemical compound, replacing its central core Research Foundation, Australian Research stability or absorption by the body. with another. Interestingly, a detailed Council and the Victorian Government. For some time, scientists from picture provided by our Structural the Chemical Biology division have Biology colleagues of how the newly More information: Sleebs BE, Czabotar collaborated with industry partners created compound binds explains why PE, Fairbrother WJ, Fairlie WD, Flygare Genentech, a member of the Roche group, its activity is subtly different from the JA, Huang DC, Kersten WJ, Koehler MF, and Abbott to develop compounds that parent compound.” Lessene G, Lowes K, Parisot JP, Smith BJ, target the Bcl-2 proteins. These proteins Associate Professor Baell said the new Smith ML, Souers AJ, Street IP, Yang H have been implicated in a number agent represents the second-known class and Baell JB. Quinazoline sulfonamides of cancers, including leukaemia and of validated Bcl-2 inhibitors. as dual binders of the proteins B-cell breast cancer. “There is intense interest in finding lymphoma and B-cell lymphoma extra In 2011, Dr Brad Sleebs, Associate new anti-cancer compounds that target long with potent proapoptotic cell-based Professor Baell and their collaborators Bcl-2,” he said. “Our ability to manipulate activity. Journal of Medicinal Chemistry. published a paper in the Journal of them chemically enables us to improve 2011 Mar 2; 54:1914.

Chemical screening investment brings results

A Victorian Government grant of $2.06 The Chemical Biology division opportunity to take their research a step million in 2003 has been fundamental was established in 2010 to enhance closer to our ultimate goal of improving to the institute’s role in discovering research efforts that link biological human health,” said Professor Huang. new compounds that are now entering discoveries with medicinal chemistry. “The Victorian Government’s initial clinical trials. This has allowed improvements in both investment in the facility has already The money, distributed through the screening process as well as the led to some potentially exciting new the now-defunct Science Technology modifications required to progress the medications, and has enabled us to attract Innovation (STI) scheme, funded half candidate compounds into drugs. biotech collaborations to the state.” of the automated equipment in the Professor David Huang, head of the institute’s high-throughput chemical institute’s Chemical Biology division, said screening (HTCS) facility. The investment the HTCS facility undertakes around 10 highlights the importance of taking a chemical screening campaigns each year. long-term view of research development. “Discovering compounds that target The HTCS facility, located at the cancer cells has been a major focus of our institute’s Bundoora campus, allows the facility,” Professor Huang said. “We are rapid screening of large chemical libraries now seeing projects that originally started to identify compounds that have the at the HTCS facility realising molecules potential to be developed into new drugs. that are entering clinical trials, which is Until recently, it was the only such an exciting development.” facility at an Australian academic The HTCS facility has also been central institution, and has been in high demand to efforts to discover new treatments for from many researchers within the infectious diseases including malaria. institute, as well as from our academic “The HTCS facility has provided Ms Rebecca Moss at the high-throughput and commercial collaborative partners. institute scientists with a unique chemical screening facility.

Annual Report 2010-2011 Walter and Eliza Hall Institute 15 Molecular Medicine

The Molecular Medicine division investigates the pathways that control the normal production of blood cells and how these pathways are perturbed in blood cell diseases such as leukaemia and lymphoma. We use data from genetics, genomics, proteomics and computational analyses to identify individual genes involved in regulatory pathways, with the ultimate goal of working closely with clinicians and the private sector to translate our discoveries into improvements in the diagnosis and treatment of blood diseases. Major research themes in the division include blood cell production and function, epigenetic regulation of gene expression and the study of blood cancers. Additional projects use the genetic technologies we have developed to better understand the regulation of neural stem cells and pathways that can lead to deafness. Research in Professor Doug Hilton’s laboratory centres around the molecular pathways regulating normal blood cell production. Mature blood cells are generated by a population of stem cells which are also capable of self-renewal. Laboratory heads Traditionally, mature blood cells and blood stem cells were thought to exist as Dr Marnie Blewitt two separate populations, with little communication. In a project spear-headed Dr Ross Dickins by Dr Carolyn de Graaf, we showed that mature blood cells can communicate Professor Doug Hilton back to their stem cell ‘parents’, changing the stem cells’ gene expression and Division head influencing their behaviour. Using new-generation genomic technologies the team also defined gene signatures underlying defective signalling in blood stem Dr Samir Taoudi cells. This information could be used to diagnose and treat blood diseases in Dr Tim Thomas the future. Dr Anne Voss Dr Samir Taoudi, the division’s newest laboratory head, is focusing on how an embryo produces the earliest stem cells. He recently showed that a gene PhD student Ms Farrah which is frequently hijacked by prostate cancer cells, Erg, plays a central role El-Saafin (below left) in maintaining blood stem cell numbers during embryonic development Dr Samir Taoudi (below right) and ensuring adequate stem cells exist to fully equip the adult in later life has shown how the gene Erg (see opposite page). This study emphasised the crucial role that Erg plays in plays a central role in blood maintaining healthy stem cells in times of stress. stem cell maintenance.

16 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Erg gene key to blood stem cell ‘self-renewal’

Blood stem cells produce and “One of the key features of blood ‘switch on’ expression of particular sets maintain the blood system throughout stem cells, one that could be exploited of genes, encouraging the stem cells to an organism’s lifetime. They are for therapeutic use, is their ability to expand, essentially creating your own multipotent cells, meaning they are regenerate or renew themselves. However, endless supply of blood stem cells,” able to form any cell of the blood, and relatively little is known about how this he said. they self-renew, so they are a source of occurs, or the molecular pathways that endless supply. specifically control regeneration,” he said. Funding partners: National Health and One major barrier to their therapeutic The team found that during Medical Research Council, Australian use is that stem cells can only be isolated development, Erg was not needed for the Cancer Research Foundation, Australian in numbers too low for practical use. original blood stem cells to be made, or to Stem Cell Centre, Australian Research Efforts to expand their number often produce mature blood cells. “But without Council, The Sylvia and Charles Viertel cause them to turn into more mature cells. Erg, these new blood stem cells rapidly Charitable Foundation and the Victorian Dr Samir Taoudi, Professor Doug decreased as they divided to produce Government. Hilton and colleagues have begun to more blood, so that they were almost unravel how blood stem cells regenerate completely exhausted by the time the More information: Taoudi S, Bee T, themselves, identifying a key gene mouse was born,” he said. Hilton A, Knezevic K, Scott J, Willson required for the process. The practical aim of the research is TA, Collin C, Thomas T, Voss AK, The discovery that the Erg gene is vitally to aid in the development of stem cell Kile BT, Alexander WS, Pimanda important to blood stem cells’ unique therapies, Dr Taoudi said. JE, Hilton DJ. ERG dependence ability to self-renew could give scientists “At the moment, if you take stem cells distinguishes developmental control of new opportunities to use blood stem cells from a person and try to expand them, hematopoietic stem cell maintenance for tissue repair, transplantation and other many of the stem cells lose their ability to from hematopoietic specification. Genes therapeutic applications. Dr Taoudi said regenerate. We are trying to find ways in & Development. 2011 Feb 1; 25(3):251-62. the research aimed to understand how which you could take stem cells collected blood stem cells are made. from bone marrow or cord blood and

‘Hairpin’ research hope for blood cancers

Leukaemia is a cancer of the blood cells normal blood cells and leukaemia cells agents, in particular for leukaemias and and is the eighth most common type of remain untested.” lymphomas, and help match the genetic cancer in Australia. In 2010, Dr Dickins’ research profile of a tumour with the best possible Dr Ross Dickins, a laboratory head was boosted by a $1 million Viertel therapeutic agent to treat that tumour,” in the Molecular Medicine division, Fellowship. The fellowship is awarded by Dr Dickins said. is investigating the genes involved The Sylvia and Charles Viertel Charitable in leukaemia development to better Foundation, one of the largest charitable understand the genetic changes that foundations in Australia. bring about leukaemia. He uses short Dr Dickins said it was an honour to be ‘hairpin’ RNA (shRNA) techniques named the 2010 Viertel Fellow. “Charles that he developed in his laboratory to Viertel was a hugely generous Australian help identify the function of genes by philanthropist, yet during his lifetime switching genes on and off to discover he sought little public recognition. It is their function. a great privilege to receive a fellowship “The techniques harness a natural from the charitable foundation he process of gene silencing known as RNA established,” he said. interference and allow us to quickly and Dr Dickins said the fellowship effectively study multiple cancer genes would support research to identify in new ways,” Dr Dickins said. “We are new therapeutic targets for cancer. examining several genes that are known “Ultimately, we hope that shRNA to be altered in human leukaemia, along technology will accelerate cancer drug Dr Ross Dickins was awarded a Viertel with a new set of genes that are thought discovery by identifying genes that Fellowship to further his research into to be involved but whose functions in could be targeted by new therapeutic the genes responsible for leukaemias.

Annual Report 2010-2011 Walter and Eliza Hall Institute 17 Structural Biology

Our research contributes to the discovery of new medicines through studies of the three-dimensional structures of large biological molecules that are either targets for drugs or potential therapeutic agents in their own right. The division’s focus on apoptosis, or programmed cell death, is motivated by the belief that the Bcl-2 protein family, which controls apoptosis, is an important target for anti-cancer drugs. The highest impact work from the division this year was from Dr Doug Fairlie’s laboratory. His discovery of a mammalian-like cell death pathway in schistosomes (see opposite page) could open up new avenues Laboratory heads for treatment of the deadly parasitic disease schistosomiasis, which is a significant health problem in developing countries. Dr Jeff Babon This year, research in our division also revealed how complexes form Dr Matthew Call between the pro-apoptotic protein Bax and pro-survival proteins Bcl-xL Dr Melissa Call and Mcl-1. Using crystal structures of the molecules we showed that formation of the complexes requires a significant conformational change in Professor Peter Colman Division head Bax. This could have implications for drug targeting and development. Our researchers also look at viral proteins that block the intrinsic Dr Doug Fairlie cell death pathway by mimicking Bcl-2 proteins in order to prevent the Dr Tom Garrett immune system from killing virus-infected cells. We found, contrary to Dr Jacqueline Gulbis expectations, that the Epstein-Barr virus (EBV) protein BHRF1 binds pro- apoptotic BH3-only proteins in the same manner as Bcl-2 does, making Associate Professor Mike Lawrence BHRF1 a potential drug target for treating EBV. Dr Brian Smith Late in 2010 we welcomed new faculty members Drs Matthew and Dr Colin Ward Melissa Call from Harvard University. In July 2011 Dr Brian Smith departed to a faculty position at La Trobe University and we look forward Dr Erinna Lee (below left) and to continuing to collaborate with him. Dr Tom Garrett retired during the Dr Doug Fairlie have identified year after a career of landmark discoveries on the structure and function of a programmed cell death cell surface receptors. pathway in parasitic worms.

18 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Worm ‘cell death’ discovery could lead to new drugs for deadly parasite

Schistosomiasis is a deadly parasitic structure of a key schistosome cell death understood about the cell death process disease of the developing world, which molecule was very similar to the protein in fluke worms before this became ranks with malaria and tuberculosis as that controls the process in humans, a reality. a major source of human illness. More which could potentially guide future than 200 million people are currently efforts to design therapeutic agents.” Funding partners: National Health and affected by the disease, and an estimated Dr Lee said the team is currently Medical Research Council, Australian 200,000 people die from it each year. exploring the possibility that so-called Cancer Research Foundation, The Dr Erinna Lee and Dr Doug Fairlie ‘BH3-mimetic’ agents could be used for Leukemia & Lymphoma Society (US), study programmed cell death in human treating schistosomiasis. BH3-mimetics Leukaemia Foundation of Australia, ANZ cells, and have recently started studying target the cell death pathway in humans Trustees, The CASS Foundation Limited the process in schistosomes, the parasitic and are currently being trialled as anti- and the Victorian Government. fluke worms that cause schistosomiasis. cancer treatments. Dr Fairlie said that the group has “We have found that a BH3-mimetic More information: Lee EF, Clarke shown that the cell death machinery that compound called ABT-737 binds to OB, Evangelista M, Feng Z, Speed TP, exists in fluke worms is unexpectedly at least one schistosome pro-survival Tchoubrieva EB, Strasser A, Kalinna BH, similar to the cell death pathway in protein, suggesting it is feasible that BH3- Colman PM and Fairlie WD. Discovery human cells. like molecules could also be developed for and molecular characterization of a “We found that schistosomes have treating schistosomiasis, and potentially Bcl-2–regulated cell death pathway in a complex cell death mechanism that other parasitic worm infections,” she said. schistosomes. Proceedings of the National relies on a delicate balancing act of pro- Although the discovery could lead Academy of Sciences USA. 2011 Apr 26; survival and pro-death molecules, just to exciting new possibilities for the 108(17):6999-7003. like in humans,” Dr Fairlie said. “We also treatment of parasitic worm diseases, determined that the three-dimensional Dr Fairlie said there was still a lot to be

Improving insulin for treating diabetes

Type 1 diabetes is a lifelong disease that better understanding of how the insulin “We would hope that, in the future, we affects more than 122,000 people in receptor functions.” could potentially see therapeutics available Australia and is increasing at a rate of In 2010, Associate Professor Lawrence for treating diabetes which mimic insulin 3.2 per cent per year. received a $60,000 grant from the but offer better glycaemic control,” Insulin is used successfully to manage Diabetes Australia Research Trust Associate Professor Lawrence said. type 1 diabetes, however it requires (DART) to fund his studies, which use daily injections and comes with other electron microscopy to study how insulin potentially fatal side effects, such as low binds to the insulin receptor on the blood sugar (hypoglycaemia). Associate surface of cells. Professor Mike Lawrence from the Established by Diabetes Australia in institute’s Structural Biology division 1987, DART supports and develops the is researching the way insulin interacts field of diabetes research in Australia with cell surface receptors with the long- by providing funding towards the term goal of devising new treatments prevention, management and cure for diabetes. for diabetes. “To enable the development of new Associate Professor Lawrence is using and improved therapeutic alternatives cryo-electron microscopy to determine for treating diabetes, it is essential to the structure of the insulin–receptor understand how insulin binds to the complex, which allows the structure insulin receptor,” Associate Professor to be viewed in a state that is as close Lawrence said. as possible to that which exists in the “Through this work, we hope to be able body. He said it might be possible to use to define the binding sites of insulin on this information for the design of new the insulin receptor and details of the therapies, which could act like insulin binding interactions, which will give us a with improved pharmaceutical properties. Associate Professor Mike Lawrence

Annual Report 2010-2011 Walter and Eliza Hall Institute 19 Bioinformatics

The past year has seen an enormous growth in the Bioinformatics division’s efforts in the analysis of massively parallel DNA sequencing (MPS) data. What was a strong trend a year ago has grown to a near- universal preoccupation at present, as more and more colleagues embrace this rapidly developing and exciting technology. MPS is a type of ultra-high-throughput sequencing which is approximately 100 times faster than the previous gold standard technologies. Our efforts in this area include consulting on the design and analysis of future MPS studies, collaborating on the analysis of MPS data from projects around the world, and developing novel analytical techniques and software. Professor Gordon Smyth and his laboratory have continued the development of new MPS analysis methods, including a software package called edgeR. Dr Tony Papenfuss has been analysing MPS data in a variety of collaborative projects, including studies of Tasmanian devil facial tumour disease and genomic rearrangements of human tumours. He has also been looking at immune gene expression in the Australian flying fox, which is the natural host of Hendra virus Laboratory heads and Australian bat lyssavirus. Dr Melanie Bahlo Dr Melanie Bahlo and her team have been using MPS data to map genes Dr Tony Papenfuss predisposing to disease. Professor Terry Speed has been working with collaborators Professor Gordon Smyth at the University of California, Berkeley, on identifying binding sites of transcription factors, and studying biases in MPS data. Professor Terry Speed Division head In addition to the explosion of new MPS data, the division has been continuing with more traditional bioinformatics research. Ms Katherine Smith and Dr Melanie Bahlo identified the gene responsible for the rare but fatal Kufs disease (see opposite Dr Melanie Bahlo (below right) page). With Dr Di Wu, Professor Smyth has published a novel statistical test that and PhD student Ms Katherine assesses the behaviour of larger biological processes instead of individual genes. Dr Smith used innovative approaches to identify the Papenfuss has had success in discovering gene families in mammals, including the gene responsible for Kufs genes which produce venom in the platypus, while Professor Speed has continued disease, a rare but fatal his studies of oestrogen biology with collaborators in the United States. hereditary brain disorder.

20 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

New technology finds gene responsible for Kufs disease

Kufs disease is a rare but fatal Dr Bahlo’s innovative work used data Collaborating organisations: hereditary neurodegenerative disease, generated from a person’s DNA, called The University of Melbourne, C. affecting approximately one in one SNP genotyping. When combined with Besta Neurological Institute, McGill million people. sophisticated mathematical and statistical University, Université de Montréal, Brain symptoms result from a build analyses, the information helped identify Liverpool Hospital, University of Catania, up of fat in brain cells that is toxic to the region in the human genome likely Beaumont Hospital, University Magna the cells, causing symptoms including to contain the DNA error that causes Græcia, University of Modena and Reggio epilepsy, dementia, impaired motor Kufs disease. Emilia, University College London. function and intellectual deterioration. “The genetic cause of Kufs disease has Dr Melanie Bahlo and colleagues from remained a mystery for over 25 years, Funding partners: National Health the institute’s Bioinformatics division, because the rarity of the condition meant and Medical Research Council, Battens with neurologist Professor Sam Berkovic that our patient groups were so small we Disease Support & Research Association from The University of Melbourne, have couldn’t reliably pinpoint any particular and the Victorian Government. used innovative new technologies to genetic mutations that caused their identify that mutations in the CLN6 gene disease,” Dr Bahlo said. “Discovering the More information: Arsov T, Smith KR, are the cause of inherited recessive Kufs CLN6 gene as the cause of Kufs disease is Damiano J, Franceschetti S, Canafoglia type A disease. a great outcome for us and for the people L, Bromhead CJ, Andermann E, Vears Professor Berkovic said identification who are affected by this awful disease.” DF, Cossette P, Rajagopalan S, McDougall of the CLN6 gene would enable more Dr Bahlo said the approach used to A, Sofia V, Farrell M, Aguglia U, Zini efficient and much less invasive techniques find the gene responsible for Kufs disease A, Meletti S, Morbin M, Mullen S, for earlier diagnosis of Kufs disease. could hold the key for finding the genetic Andermann F, Mole SE, Bahlo M, “Currently, the only way that we can cause of a number of other hereditary Berkovic SF. Kufs disease, the major adult diagnose this disease is to do an invasive diseases including other epilepsy- form of neuronal ceroid lipofuscinosis, and dangerous brain biopsy,” Professor related diseases, deafness and some caused by mutations in CLN6. American Berkovic said. “This discovery will enable familial cancers. Journal of Human Genetics. 2011 May 13; us to use a rapid and simple blood test to 88(5):566-73. genetically test for the disease.”

Sir John Monash scholarship to fund Oxford PhD studies

Bioinformatician Mr Davis McCarthy our contributions can be wide-ranging cells and healthy cells as a step towards has been awarded a $150,000 and profound.” understanding the mechanisms by which scholarship from the General Sir John Recent advances in biology have been cancer evades the body’s defence system,” Monash Foundation that has made it driven by the development of ultra-high- he said. possible for him to start his PhD at the throughput DNA sequencing technologies University of Oxford, UK, in 2011. that allow biologists to investigate the As an undergraduate and honours differences in thousands of genes at once. student in the Bioinformatics division, The outcome of this is the generation of Mr McCarthy was a key member of the an overwhelming amount of data. edgeR project (see opposite page). He will “Making sense of this deluge of data undertake his PhD in the Department presents a real challenge,” Mr McCarthy of Statistics at Oxford, home to several said. “Statisticians aim to help biologists leading researchers in the field who obtain as much useful information actively collaborate with the institute from their data as possible by providing bioinformaticians. robust statistical analysis techniques “The work I propose for my PhD will implemented in easy-to-use, well- help biologists to develop treatments documented, public software.” for diseases such as cancer, malaria, Mr McCarthy said there are many and diabetes,” Mr McCarthy said. possible applications. “We can, for “Statisticians may operate behind the example, investigate which genes are scenes in improving human health, but ‘differentially expressed’ between tumour Mr Davis McCarthy

Annual Report 2010-2011 Walter and Eliza Hall Institute 21 Infection and Immunity

Infectious diseases caused by parasites, bacteria and viruses are a major global health burden resulting in death, disability, and social and economic disruption for hundreds of millions of people. Malaria, tuberculosis and HIV are three infectious diseases that cause significant death and disability, particularly in resource-poor countries. In the Infection and Immunity division we aim to understand how infectious agents cause disease in humans and to use this knowledge to develop new treatments. A highlight of the division this year has been our work on understanding the factors that impede immune responses to persistent virus infections such as HIV. A team led by Dr Marc Pellegrini identified that the cell signalling protein interleukin-7 is a potential therapeutic agent for the treatment of chronic viral diseases such as HIV (see Laboratory heads opposite page). The discovery, using a mouse model infected with the virus LCMV (lymphocytic choriomeningitis virus), has enabled an understanding Dr Alyssa Barry of the inhibitory pathways underlying impaired antiviral immune responses. Dr Jacob Baum The division continues to make discoveries and advances in the Dr James Beeson understanding of malaria. The malaria-causing Plasmodium parasite infects humans by invading red blood cells, where it can access the nutrients Professor Alan Cowman Division head it requires for survival. An important aim of the division has been to understand how the parasite infects a red blood cell. The advent of super- Dr Diana Hansen resolution microscopy has allowed us to visualise and dissect the steps in this Professor Ivo Mueller host-cell invasion process. The ability to break down each molecular step Dr Marc Pellegrini has enabled us to build a comprehensive model for the molecular basis of Associate Professor Louis Schofield parasite invasion. We have made further inroads into understanding this invasion process by Dr Chris Tonkin identifying complement receptor-1 on the red blood cell as a major receptor to which the malaria parasite binds using the protein PfRh4. This allows the Dr Jake Baum (below left) and parasite to identify the appropriate cell to enter, resulting in activation of the PhD student Mr David Riglar multiple steps in the invasion process. Dr Alyssa Barry (below right)

22 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Boosting immune response may hold key to HIV cure

Viruses such as HIV and hepatitis B T cells. “In an overwhelming infection Sparwasser T, Tedder TF, Paik J, DePinho and C often lead to the establishment such as HIV and hepatitis B and C, RA, Basta S, Ohashi PS, Mak TW. IL-7 of incurable, lifelong infections due SOCS3 becomes highly activated and engages multiple mechanisms to overcome to the immune system’s inability suppresses the immune response, probably chronic viral infection and limit organ to effectively respond to and clear as a natural precaution to prevent tissue pathology. Cell. 2011 Feb 18; 144:1-13. the virus. damage. IL-7 treatment during a viral Despite tremendous efforts from the infection switches SOCS3 off, boosting immune system, particularly T cells, T cell numbers and function so that the these viruses are able to establish chronic immune system can successfully fight the infections by overwhelming the immune virus until it is cleared,” Dr Pellegrini said. system to the point where it is overrun The finding could lead to a cure for and effectively ‘gives up’ on fighting HIV, hepatitis B and C, and bacterial the infection. infections such as tuberculosis, which However, in a 2011 Cell paper, Dr Marc are significant economic and global Pellegrini and colleagues Mr Jesse Toe health burdens. and Mr Simon Preston showed that they were able to successfully clear an HIV- Collaborating organisations: Ontario like infection in mice by reinvigorating T Cancer Institute, Cytheris Inc, Stanford cell responses to the virus. University, TWINCORE – Centre for Dr Pellegrini said treatment with a cell Experimental and Clinical Infection signalling protein called interleukin-7 Research, Duke University, Harvard (IL-7) boosted the immune response University, Queen’s University. to virus infection, allowing the mice to completely clear the virus. “We found that Funding partners: National Health IL-7 boosted the immune response in a and Medical Research Council, Canadian profound fashion, such that animals were Institute for Health, Cancer Research able to gradually clear the virus without Institute and the Victorian Government. too much collateral tissue damage,” A collage showing progressive clearance of virus (green) due to treatment he said. More information: Pellegrini M, with IL-7. T cells (white/brown) are Further investigations revealed that, Calzascia T, Toe JG, Preston SP, Lin superimposed on the virus-infected at the molecular level, IL-7 worked by AE, Elford AR, Shahinian A, Lang PA, cells, with a ‘halo’ of IL-7 boosting their switching off a gene called SOCS3 in Lang KS, Morre M, Assouline B, Lahl K, ability to fight and eliminate virus.

Unravelling the secrets of malaria

Malaria is a devastating parasitic Dr Boddey said his Ramaciotti grant “Vera made a significant and lasting infection. Every year, Plasmodium would help to answer basic, fundamental contribution to the Australian scientific parasites infect more than 600 questions about how malaria infects cells. community through her decision to create million people worldwide, resulting “We are interested in looking at the a charitable trust 40 years ago,” he said. in almost one million deaths, early stages of human infection, where, “Since then, the Ramaciotti Foundations mostly children. for about a week, the parasite uses the have provided scientists with necessary Resistance to common antimalarial liver as a safe-haven to mount an attack funds for creative and cutting-edge drugs is now widespread, highlighting an on red blood cells,” he said. medical research, which often struggles to urgent need for new therapies. The Ramaciotti Foundations, attract funding from mainstream sources.” In 2010, institute researcher Dr Justin administered through Perpetual, have The Ramaciotti Foundations have Boddey was awarded a Ramaciotti been a strong supporter of the Walter donated more than $51 million to Establishment Grant of $75,000 to and Eliza Hall Institute since 1971. biomedical research in Australia and continue his research on whether the The general manager of philanthropy are collectively one of the largest private mechanism used by malaria parasites to at Perpetual, Mr Andrew Thomas, contributors to the field. renovate red blood cells is also used in the said Vera Ramaciotti was a forward- liver infection stage. thinking philanthropist.

Annual Report 2010-2011 Walter and Eliza Hall Institute 23 Immunology

Our immune system is capable of tremendous information gathering and processing; probing and responding to features of foreign material. For the immune system, decisions on how to respond to foreign or diseased cells and pathogens begin at birth and continue throughout life. In the Immunology division, our laboratories are dedicated to understanding the fascinating but complex immune system, both in its healthy state and when its processes go awry. We are motivated by the knowledge that developing accurate models of the adaptive immune response, which recreate these decision-making and control responses, will have enormous practical benefits for human health. Our scientists are working on these problems at multiple levels. We carefully dissect the behaviour of lymphocytes (a type of white blood cell) and their interactions with other cells to define the molecular components and rules governing lymphocyte function. This information is being used to derive working computer models that accurately simulate the immune response. Laboratory heads Other studies examine the regulation of immune cell function to determine Dr Bob Anderson the genetic basis of particular responses, and how these responses might be manipulated for therapeutic benefit. We are particularly interested Professor Len Harrison in understanding how antibody production is controlled, with a view to Professor Phil Hodgkin improving vaccination strategies. Division head A major area of discovery has been the development of ways to switch off Associate Professor Andrew Lew the immune response. These methods are finding application in preventing Professor Ken Shortman tissue graft rejection and type 1 diabetes. Our studies have led to a new Associate Professor David Tarlinton strategy to identify people with a susceptibility to developing type 1 diabetes, and to modify these people’s immune response to reduce their risk. Similar strategies are also being applied to coeliac disease, a problem caused by Dr Yuxia Zhang (below left) immune sensitivity to gluten in wheat and other foods. Members of the Hons student Ms Julia division are leading efforts to screen for, and eliminate, this disease. Marchingo (below right)

24 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Cell survival protein discovery rewrites immune system story

B cells are a crucial component of the establish germinal centres, as well as More information: Vikstrom I, Carotta immune system, producing a range of instructing activated B cells to become S, Luthje K, Peperzak V, Jost PJ, Glaser antibodies that fight infection. memory B cells,” Dr Vikstrom said. S, Busslinger M, Bouillet P, Strasser A, One particular group of B cells, called She said she was surprised by what they Nutt SL and Tarlinton DM. Mcl-1 is memory B cells, are essential for the found. “We studied two well-known pro- essential for germinal centre formation long-lived immunity that arises after survival proteins called Bcl-xL and Mcl-1, and B cell memory. Science. 2010 Nov 19; immunisation. To develop into memory which we knew were involved in the 330:1095-1099. cells, B cells have to survive the natural process,” Dr Vikstrom said. “It surprised process of apoptosis, or programmed cell us to find that Mcl-1 was the essential death, that occurs following a large immune pro-survival protein required for creation response. B cell memory is programmed and maintenance of B cell memory, not in temporary cellular structures called Bcl-xL as was commonly believed,” Dr germinal centres that develop in response Vikstrom said. to activation of the immune system. Associate Professor Tarlinton said the A discovery by Dr Ingela Vikstrom and discovery could have implications for Associate Professor David Tarlinton is set cancer treatment, autoimmune disease to rewrite a long-held belief about how and transplant rejection. the body’s immune system establishes memory B cells in these germinal centres. Collaborating organisations: Dr Vikstrom said so-called ‘pro- Research Institute of Molecular survival’ proteins regulate B cell survival Pathology, Vienna Biocenter. and are responsible for instructing activated B cells on whether to live or Funding partners: National Health die. “Our research used genetic and and Medical Research Council, The pharmacological methods to identify Leukemia & Lymphoma Society (US), Dr Ingela Vikstrom (above left) and Associate which pro-survival molecules were National Institutes of Health (US) and the Professor David Tarlinton are researching essential for ‘instructing’ these cells to Victorian Government. the development of immune memory cells.

EMBO fellowship supports blood cancer research

Multiple myeloma is a cancer of what goes wrong in these cells to cause International exchange is a key feature of plasma cells and is the second-most them to become cancerous.” the program. common blood cancer. It represents Dr Peperzak said plasma cells approximately one per cent of all depend heavily on the continuous cancers and two per cent of all cancer receipt of survival signals from the deaths worldwide. local environment for their long-term In 2010 Dr Victor Peperzak was survival. His research is looking at how awarded an EMBO (European Molecular these external signals affect pro-survival Biology Organization) Long-Term proteins that keep the plasma cell alive. Fellowship which allowed him to move “This project will look at whether the from the Netherlands to Australia, and the protein Mcl-1 is essential for maintaining institute’s Immunology division, to study plasma cells and how expression of the molecular signals within plasma cells. Mcl-1 changes during development,” he “Plasma cells are specialised said. “Understanding the function and in producing large amounts of expression of Mcl-1 in plasma cells and antibodies and are a crucial part of our in multiple myeloma cells might provide immune system,” Dr Peperzak said. valuable therapeutic targets for treatment “Understanding how plasma cells are of plasma cell malignancies.” able to survive and continue to produce EMBO Long-Term Fellowships antibodies for several months up to many support postdoctoral researchers visiting years is instrumental to understanding laboratories throughout the world. Dr Victor Peperzak

Annual Report 2010-2011 Walter and Eliza Hall Institute 25 Autoimmunity and Transplantation This division ceased operations on 31 December 2010.

The immune system protects the body against disease by attacking foreign threats such as infections and tumours. In some instances, however, the immune system mistakenly targets the body’s own tissues, causing autoimmune disease. For example, in type 1 diabetes the insulin-producing beta cells of the pancreas are targeted and damaged, and in rheumatoid arthritis the joints. In coeliac disease, the immune system damages the gut by reacting to a foreign protein, gluten, present in wheat and other cereals. The division investigates the genetic and environmental factors leading to inflammatory diseases, as well as the underlying mechanisms, to improve disease prevention and treatment. We also investigate ways to temper immune responses to prevent rejection of transplanted tissue grafts, how inflammation in fat tissue in obese people leads to insulin resistance and diabetes, and whether stem cells in the pancreas can be used as a source of insulin-producing cells to treat type 1 diabetes. Our research uses a broad range of molecular and cellular technologies, as well as mouse Laboratory heads models of human diseases. Laboratory research is complemented by strong ties with Dr Bob Anderson clinical medicine – three of our laboratory heads hold appointments at Melbourne Health Professor Len Harrison or Bayside Health, facilitating translation of research to human health. Division head Research highlights in the past year include: demonstrating the safety, tolerability and bioactivity of a peptide-based vaccine for coeliac disease (in collaboration with Associate Professor Andrew Lew commercial biotechnology partner ImmusanT); the discovery that monocyte-derived Professor Ian Wicks dendritic cells are key producers of the blood cell hormone (cytokine) interleukin-12 during inflammation; demonstrating that antagonists of the pro-survival Bcl-2 family Dr Melinda Hardy (below have therapeutic potential in autoimmune arthritis; evidence in human obesity that left), Dr Bob Anderson (below inflammatory cells in the fat tissue produce factors that block the actions of insulin; centre) and Dr Jason Tye- discovery of a mechanism that explains how some immune cells dampen inflammation; Din are trying to find new and demonstrating in humans that a nasal insulin vaccine desensitises the body to insulin. therapies for coeliac disease.

26 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Nasal vaccine for type 1 diabetes shows promise

Type 1 diabetes occurs when the body’s immune system, suppressing its reaction Collaborating institution: The Royal immune system attacks and kills beta against insulin. Their research provides Melbourne Hospital. cells – the cells in the pancreas that proof-of-principle for the type 1 diabetes produce insulin. prevention trial, also called the intranasal Funding partners: Melbourne Crucially, insulin itself is a specific insulin trial II (INIT II), being conducted Health, National Health and Medical target of the immune attack that kills the in Australia, New Zealand and Germany. Research Council, Juvenile Diabetes beta cells. Lack of insulin leads to serious “The results showed that the vaccine Research Foundation, Diabetes Vaccine health problems and people with type 1 allowed the immune system to restore Development Centre (Garvan Institute diabetes require daily insulin injections. immune tolerance to insulin, and of Medical Research) and the Victorian A nasal spray vaccine could prevent the encourages us that we are on the right Government. development of type 1 diabetes in people track to finding a vaccine for type 1 at risk of getting the disease. diabetes,” Professor Harrison said. More information: Fourlanos S, Professor Len Harrison from the “The nasal insulin vaccine works Perry C, Gellert SA, Martinuzzi E, institute and Professor Peter Colman to desensitise the immune system Mallone R, Butler J, Colman PG, and Dr Spiros Fourlanos from The Royal to insulin, which we hope will prevent Harrison LC. Evidence that nasal insulin Melbourne Hospital have provided the a subset of white blood cells, called T induces immune tolerance to insulin first evidence in humans that the nasal cells, from attacking insulin in the beta in adults with autoimmune diabetes. insulin vaccine desensitises the human cells of the pancreas.” Diabetes. 2011 Apr; 60(4):1237-45.

The J.H.A. Munro Foundation – supporting diabetes research

Mr Bob Munro understands what it Harrison’s work at the institute into the “Professor Harrison and his research is like to have a family affected by role of vitamin D in diabetes. Vitamin team and even institute director Professor serious illness. D is a steroid hormone with anti- Doug Hilton took the time to explain the With a son who has severe type 1 inflammatory properties, and has been research to me, and I felt I could be part diabetes, Mr Munro decided he wanted shown to improve the function of insulin of the solution,” he said. to make a difference to people suffering production in humans. from this chronic disease, and aid in the Professor Harrison, with fellow identification of causes and treatments institute clinician researchers Dr Shirley for diabetes. Type 1 diabetes is a lifelong Elkassaby and Dr John Wentworth, inflammatory disease requiring daily and Dr Spiros Fourlanos from The injections of insulin. Royal Melbourne Hospital, has been For several years Mr Munro, through investigating whether vitamin D improves the J.H.A. Munro Foundation, has immune and metabolic function in people supported the work of Professor Len with diabetes. Harrison. Professor Harrison has joint Mr Munro’s foresight and generosity appointments at the institute, where he in supporting the research made the leads the diabetes research program, and project viable. at The Royal Melbourne Hospital (RMH), “I wanted to put my money into where he is a member of the Department research which would make a difference of Diabetes and Endocrinology. to people suffering from diabetes,” Mr Initially, Mr Munro supported Munro said. the work of Professor Harrison and As results from the study became Professor Peter Colman (from RMH) available in late 2010, the institute in their development of a nasal vaccine arranged for Mr Munro to come in for an for type 1 diabetes. This association update on the research. Mr Bob Munro, supporting diabetes led to Mr Munro supporting Professor research at the institute.

Annual Report 2010-2011 Walter and Eliza Hall Institute 27 Cell Signalling and Cell Death This division began operations in January 2011.

The ultimate fate of most of our cells is not to wear out or be killed, but to self-destruct in a process that has evolved specifically to maintain the correct number of cells, or remove those that are unhealthy or unwanted. By determining how this process occurs at a molecular level, as well as the signalling pathways that control it, we seek to find new ways of preventing the death of cells in cases where it is inappropriate, such as in neurodegenerative diseases, or restart the process when it fails, such as in some cancers or in certain autoimmune diseases. The Cell Signalling and Cell Death division officially started in January 2011, but members of the division have had a long association with the institute. Associate Professor John Silke studies proteins called ubiquitin ligases to decipher their roles in blood cell hormone (cytokine) signalling and protein turnover, and Associate Professor Paul Ekert is focusing on leukaemias and the role of Hox and Bcl2-family genes in the development of leukaemia. Dr Grant Dewson works with Dr Ruth Kluck from the Molecular Genetics of Cancer division to investigate how Bax and Bak proteins operate, while Professor David Vaux focuses on RIP kinases, which can activate both caspase- Laboratory heads dependent and independent cell death mechanisms in response to cytokines such as tumour necrosis factor. Dr Grant Dewson A major focus of the division is understanding the mechanisms of cell Associate Professor Paul Ekert death, including a family of cell death-inhibitory proteins known as IAPs. As Associate Professor John Silke the IAP genes are frequently amplified in cancers, we are studying how they keep tumour cells alive, as well as looking at the role of IAPs during cancer Professor David Vaux Division head development and in healthy cells. Our identification, several years ago, of a natural IAP-antagonist led to development of IAP-antagonist compounds (also known as ‘smac-mimetics’). We are studying how these compounds, which are Associate Professor Paul currently in phase I clinical trials for the treatment of cancer, not only block Ekert (below left) IAP protein function, but cause IAPs to disappear from within the cell. Dr Kate Lawlor (below right)

28 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Understanding how TNF controls cell signalling

Members of the tumour necrosis factor very significant for the field,” Associate More information: Gerlach B, Cordier (TNF) family of signalling molecules Professor Silke said. “The number, SM, Schmukle AC, Emmerich CH, (cytokines) play an important role in the length and linkage of these ubiquitin Rieser E, Haas TL, Webb AI, Rickard immune response and inflammation. chains forms a language that we are just JA, Anderton H, Wong WW, Nachbur TNF is a vital immune system protein beginning to decipher.” U, Gangoda L, Warnken U, Purcell AW, that controls the function of immune Associate Professor Silke said the Silke J, Walczak H. Linear ubiquitination cells, stimulates early immune responses team unexpectedly found that the prevents inflammation and regulates to bacterial and viral infections, and absence of the Sharpin gene induced immune signalling. Nature. 2011 Mar 31; inhibits tumour development. a severe inflammatory skin disease in 471(7340):591-6. Associate Professor John Silke and mouse models. Dr Andrew Webb are looking at how “Mice without the Sharpin gene This work was carried out by members of TNF signalling molecules function and had weaker TNF signalling responses, the Cell Signalling and Cell Death division interact, which could have potential however this actually produced a strong while the staff were at the Department implications for treating inflammatory inflammatory reaction, which was of Biochemistry at La Trobe University, diseases and cancer. alleviated when TNF genes were switched Melbourne. Associate Professor Silke said the off,” Associate Professor Silke said. “This research, published in the journal was a surprising result, because you Nature, described the discovery of a would think that weaker TNF signals new gene involved in TNF signalling. would reduce the inflammatory reaction, “We identified for the first time that a but it appears the body compensates for protein called SHARPIN is involved in this by producing other inflammatory the signalling pathway, and interacts with cytokines,” he said. two previously identified proteins, HOIL- 1 and HOIP, to form a ubiquitin ligase Collaborating organisations: Imperial complex,” he said. College London, German Cancer “The ubiquitin ligase complex is Research Center, Mediterranean Institute important for attaching ubiquitin of Oncology, and Bio21 Institute. molecules to proteins in a linear chain that ‘tags’ the proteins for alteration, Funding partner: National Health and relocation or destruction. The Medical Research Council. identification of this linear chain was Associate Professor John Silke

Remembering Philip Hemstritch (23 July 1951 – 17 March 2010)

In 2010, when Mrs Jane Hemstritch With a background in accounting and In looking at the research streams she first visited the Walter and Eliza Hall science, Mrs Hemstritch was asked to join could support, Mrs Hemstritch settled Institute, she had an intense discussion the institute’s Financial Sustainability on the work undertaken by the institute’s with institute director Professor Committee in April 2011 to help raise Cell Signalling and Cell Death division, Doug Hilton and head of fundraising funds to support the sort of critical led by Professor David Vaux. Professor Ms Deb Cutts about the institute’s clinical research that will improve the Vaux’s work focuses on apoptosis, or research aspirations. lives of people with all types of cancer. programmed cell death. “I visited the cancer research She also decided to make a significant A discovery Professor Vaux made 20 laboratories and had a great discussion donation to cancer research in honour years ago has led to the development of with Doug and Deb about the institute’s of her husband Philip who died in 2010 a potential new anti-cancer agent that cancer research, which aimed to explore after a two-and-a-half year battle with is now entering clinical trials to treat the behaviour of cancer in order to pancreatic cancer. “I looked into the chronic lymphocytic leukaemia, the develop innovative new treatments,” Mrs research that the institute was doing most common type of leukaemia. Mrs Hemstritch said. “I was eager to help to better understand cancers that arise Hemstritch’s support of his division will support the institute in any way I could to from mutations that help tumour cells to assist in this research. see them achieve this mission.” survive,” Mrs Hemstritch said.

Annual Report 2010-2011 Walter and Eliza Hall Institute 29 Inflammation This division began operations in January 2011.

Inflammation is a rapid, protective response to noxious stimuli. A wide variety of stimuli can induce inflammation and an intricate system of recognition receptors, immune cells and mediators coordinate and control the response in affected tissues and the body. Short-term inflammation is usually beneficial to the host, but can be catastrophic if not controlled appropriately. Increasing evidence suggests persistent, low-grade inflammation is likely to contribute to many common diseases, including autoimmune and metabolic conditions, and cancer. In the Inflammation division we study the biological and molecular mechanisms underlying inflammatory diseases in order to improve prevention and treatment. We are interested in acute and chronic infections, autoimmune diseases (such as rheumatoid arthritis, vasculitis and rheumatic fever) and metabolic diseases (such as atherosclerosis and gout). We study cell signalling proteins (cytokines), immune cells and molecular regulators of inflammation using a wide range of experimental techniques. We have strong connections to hospitals, facilitating translation of research to human health. Research highlights from the division in its first six months include describing how a cytokine discovered at the institute, granulocyte-macrophage colony stimulating factor (GM-CSF), coordinates the recruitment and differentiation of a type of dendritic Laboratory heads cell that promotes ongoing inflammation. Recent studies of the iNOS enzyme, which Dr Ben Croker catalyses the production of nitric oxide to kill pathogens, have demonstrated that a Dr Sandra Nicholson molecule known as SPSB1 regulates iNOS during the early response to pathogens. Our division has also developed an automated high-throughput live cell-imaging Dr José Villadangos platform to examine cell survival. We have demonstrated that the Bcl-2 family of cell Professor Ian Wicks death proteins can directly regulate the Fas death receptor pathway in neutrophils, Division head highlighting novel avenues to control apoptosis during inflammatory disease. Currently under study are the molecular mechanisms underlying the regulation Dr Sandra Nicholson of cystatin C, a protein that has been linked to atherosclerosis and is regulated by (below left) inflammatory stimuli through expression of the transcription factor IRF8. This may PhD student Dr Simon lead to development of therapeutic treatments to prevent atherosclerosis. Chatfield (below right)

30 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Defining the molecular ‘conversations’ leading to inflammatory disease

Chronic inflammatory diseases such as “Understanding how these cytokines research could have opened a whole new rheumatoid arthritis are a major health can be manipulated to treat chronic field of treatment to help these patients. burden in Australia. inflammatory diseases is an exciting field We are also hopeful that inhibitors of Dr Ian Campbell, Ms Annemarie which is already leading to new agents GM-CSF signalling might have fewer, van Nieuwenhuijze and Professor Ian entering clinical trials.” and more manageable, side effects than Wicks in the Inflammation division The current study has shown that a current treatments.” have discovered a biological sequence of subset of immune cells called ‘helper T events that leads to the development of cells’ produces GM-CSF, which drives Funding partners: John T Reid inflammatory disease. the formation of other immune cells, Charitable Trusts, Arthritis Foundation The studies build on longstanding called inflammatory dendritic cells, that of Australia, National Health and Medical research headed by Professor Wicks, exacerbate joint inflammation. This work Research Council, Cancer Council which has explored the roles of was facilitated by collaboration with the Victoria, European Commission and the the molecules (cytokines) G-CSF dendritic cell group, headed by Dr José Victorian Government. (granulocyte colony stimulating Villadangos. Treatments that stop this factor) and GM-CSF (granulocyte- molecular communication between the T More information: Campbell IK, van macrophage colony stimulating factor) cells and the inflammatory dendritic cells Nieuwenhuijze A, Segura E, O’Donnell in mediating the joint inflammation that may be able to reduce the inflammation K, Coghill E, Hommel M, Gerondakis S, causes arthritis. that causes rheumatoid arthritis, said Villadangos JA, Wicks IP. Differentiation “The role of G-CSF and GM-CSF Professor Wicks. of inflammatory dendritic cells is in blood cell formation have been well “Currently, around half of patients mediated by NF-κB1-dependent GM-CSF defined by a large body of research by do not respond adequately to available production in CD4 T cells. Journal of institute scientists, in particular Professor therapies for arthritis,” he said. “As a Immunology. 2011 May 1; 186(9):5468-77. Don Metcalf,” said Professor Wicks. rheumatologist, I am very excited that our

Arthritis research program flourishes under long-term support

Rheumatoid arthritis is a major cause of “G-CSF and GM-CSF were both this disease has on the community,” disability and chronic pain for around discovered at the institute as regulators Professor Wicks said. “The support of 200,000 Australians. It is estimated to of white blood cell production,” said the John T Reid Charitable Trusts has cost the community billions of dollars Professor Wicks. “Our work has opened provided my laboratory with a critical per year in direct and indirect medical a new avenue of interest into the role of support base from which we can develop care, lost earnings and productivity. these cytokines in inflammation, which long-term research strategies that The institute has been fortunate to we hope will lead to new treatments for span from basic discovery through to have the long-term support of the John inflammation and arthritis. clinical research.” T Reid Charitable Trusts in maintaining “Research into the causes of, and Mrs Belinda Lawson (centre), trustee of an arthritis research laboratory. The treatments for rheumatoid arthritis the John T Reid Charitable Trusts, with Reid Laboratory has been headed by remains relatively poorly supported in institute researchers including director Professor Ian Wicks since the early 1990s, Australia, despite the significant impact Professor Doug Hilton (far left) and Professor Ian Wicks (third from left). and is now part of the newly formed Inflammation division. The Reid Laboratory has made many substantial advances in understanding the molecular events underlying the development of arthritis. One highlight has been the discovery that the cytokines G-CSF and GM-CSF contribute to the joint inflammation that underlies arthritis. This research has resulted in the development of potential new treatments for arthritis that block G-CSF or GM-CSF, the latter now being in phase I clinical trials.

Annual Report 2010-2011 Walter and Eliza Hall Institute 31 Molecular Immunology This division began operations in January 2011.

Our health depends on a complex network of immune cells that perform the delicate balancing act of protecting us from attack by invading microorganisms whilst limiting the collateral damage to the body’s own cells. The Molecular Immunology division was created in January 2011 with the goal of deciphering how our immune network functions and what goes awry in conditions such as autoimmune disease and leukaemia. All cells in the immune system derive from blood stem cells that reside in the bone marrow. Major research themes of the division are to investigate how these rare stem cells generate immune system cells and how the mature components of the system such as B cells, T cells, natural killer cells and dendritic cells are programmed to undertake their specialised functions. This year we have made a number of discoveries that have improved our understanding of how this immune cell programming occurs. In a project led by Dr Gabrielle Belz we discovered that the presence of inhibitory factor Id2 is critical Laboratory heads for the decision of immature cells to become either dendritic cells, sentinels that alert the immune system to foreign invaders, or natural killer cells, which eliminate Dr Gabrielle Belz virus-infected and cancerous cells (see opposite page). Dr Sebastian Carotta Another project of long-term interest is understanding the master immune Associate Professor Lynn Corcoran regulator Blimp-1. Mice lacking Blimp-1 develop severe autoimmune disease that resembles colitis. Studies led by Drs Erika Cretney and Axel Kallies solved this Dr Axel Kallies mystery by finding that Blimp-1 controls the function of regulatory T cells. Dr Stephen Nutt Regulatory T cells provide an essential ‘balance’ to the system by preventing Division head overactive immune cells attacking the body, however there are associated problems. Dr Li Wu Impaired regulatory T cell function is linked with diseases including type-1 diabetes, because the immune system isn’t held in check, however too much Dr Gabrielle Belz (below regulatory T cell activity stops the immune system from eliminating cancer cells left) and Dr Sebastian and impedes cancer therapy. The finding that Blimp-1 controls regulatory T cell Carotta study molecular activity opens new avenues for treating these devastating diseases. signals in immune cells.

32 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Key genetic ‘switch’ gives clues about immune cell function

Natural killer (NK) cells and dendritic using this protein to characterise these Funding partners: National Health and cells (DCs) are the first line of defence in cells further, including the pathway by Medical Research Council, Australian the immune response against invading which they develop, what type of cell Research Council, Swiss National Science pathogens and tumour development. surface proteins or ‘markers’ they have Foundation, The Sylvia and Charles There are still many holes in our and the genes which are important for Viertel Foundation, Howard Hughes understanding of the biology of NK their specific function.” Medical Institute, Leukaemia Foundation cells and DCs, particularly their early Dr Carotta said that Id2 has been of Australia, Pfizer Australia and the development. Discovering how these vital in identifying early NK progenitor Victorian Government. cells progress from immature to mature populations and their development. “In immune cells will offer opportunities collaboration with Dr Belz, we were able More information: Carotta S, Pang for exploiting them as vaccine targets to use Id2 to identify and purify the SH, Nutt SL and Belz GT. Identification or therapeutic treatments for cancer, earliest known population of cells which of the earliest NK cell precursor in the inflammatory diseases or infection. are ‘committed’ to becoming NK cells, mouse bone marrow. Blood. 2011 May 19; Researchers from the Molecular which was a landmark for the field,” 117(20):5449-5452. Immunology division are working to he said. Jackson JT, Hu Y, Liu R, Masson F, further our understanding of which genes Dr Belz said that Id2 was also helping D’Amico A, Carotta S, Xin A, Camilleri are important for instructing blood stem the group map the development of MJ, Mount AM, Kallies A, Wu L, Smyth cells to produce NK cells and DCs. Dr different types of dendritic cells from GK, Nutt SL, Belz GT. Id2 expression Gabrielle Belz, Dr Sebastian Carotta and a common ancestor, and identify other delineates differential checkpoints in colleagues have been using a key immune genes involved in the process. the genetic program of CD8α(+) and protein, inhibitor of DNA binding-2 (Id2), “Our ultimate goal is to devise ways CD103(+) dendritic cell lineages. EMBO to provide insights into these elusive cells. to manipulate the production of NK and Journal. 2011 May 17; 30(13): 2690-2704. “Id2 is a critical protein in the dendritic cells to treat diseases such as immature immune cell’s decision to cancer. Understanding more about the become either a dendritic cell or a natural biology of these cells will uncover new killer cell,” Dr Belz said. “We have been ways to do this,” she said.

Swiss investment helps immune system understanding

Antibodies secreted by plasma these cells in a mature, long-lived state stay abroad in order to increase their cells are crucial for longlasting without the cell dying,” he said. knowledge and scientific reputation. protection against pathogens and for The studies will shed new light on Dr Chevrier said he is fortunate to be efficient vaccines. regulation of the immune response as supported in his studies at the institute. Plasma cell development from well as plasma cell malignancy. “Working at the institute is a great their B cell ‘parents’ has to be tightly “Identifying new factors involved opportunity for my scientific career. regulated to avoid severe diseases, such in this process and improving our Without this fellowship that pays for my as autoimmunity and cancer. Plasma cell knowledge will ultimately aid in the salary and attendance at conferences, this mutations lead to cancers such as multiple development of more efficient vaccines experience would not be possible,” he said. myeloma, which are often hard to treat as well as treatments for autoimmune and have a poor prognosis. diseases and cancers, including Dr Stéphane Chevrier and his leukaemia and multiple myeloma,” colleagues in the Molecular Immunology he said. division are interested in understanding Dr Chevrier has been with the institute the molecular signals that regulate the for two years with the support of the development of B cells into activated Swiss National Science Foundation, first antibody-secreting cells. with an 18 month prospective researcher Key aspects of this process remain fellowship, and now with an advanced elusive, Dr Chevrier said. “Little is known researcher fellowship. about the earliest changes that determine The Swiss National Science Foundation the commitment of a B cell to becoming fellowships for advanced researchers an antibody-secreting plasma cell, and the enable young scientists planning to follow mechanisms responsible for maintaining an academic career to benefit from a Dr Stéphane Chevrier

Annual Report 2010-2011 Walter and Eliza Hall Institute 33 Publications

The year ending 30 June 2011 saw the number of scientific papers from the Walter and Eliza Hall Institute reach an 11-year high, with 250 papers published. Consistent with previous years, our scientists have published in highly-ranked international journals, including Nature, Science and Cell. Forty per cent of papers published were in the top 10 per cent of their field, and 9.5 per cent in the top one per cent of their field, according to Thomson Reuters Web of Knowledge, which ranks the impact of journal papers around the world. A full list of journal papers published this year can be found on the accompanying CD. Some of our highest impact papers from the year were:

Super-resolution dissection Mcl-1 is essential for germinal center The transcription factors Blimp-1 and of coordinated events during formation and B cell memory. IRF4 jointly control the differentiation malaria parasite invasion of the Vikstrom I, Carotta S, Luthje K, Peperzak and function of effector regulatory human erythrocyte. V, Jost PJ, Glaser S, Busslinger M, Bouillet T cells. Riglar DT, Richard D, Wilson DW, P, Strasser A, Nutt SL, Tarlinton DM. Cretney E, Xin A, Shi W, Minnich M, Boyle MJ, Dekiwadia C, Turnbull L, Science. 2010 Nov 19; 330(6007):1095-9. Masson F, Miasari M, Belz GT, Smyth GK, Angrisano F, Marapana DS, Rogers KL, Memory B cells are essential for the Busslinger M, Nutt SL, Kallies A. Nature Whitchurch CB, Beeson JG, Cowman long-lived immunity that arises after Immunology. 2011 Apr; 12(4):304-11. AF, Ralph SA, Baum J. Cell Host Microbe. immunisation. The germinal centres in Regulatory T cells are responsible for 2011 Jan 20; 9(1):9-20. the spleen are temporary cell structures suppressing the immune response to Malaria is a major infectious disease of where B cells mature and develop prevent inflammatory diseases. Disorders the developing world for which there is no immunological memory so that they that decrease regulatory T cell activity current effective vaccine. A critical step in can respond more quickly when they can lead to autoimmune diseases such as the lifecycle of this parasite is the invasion encounter foreign bodies. For many type 1 diabetes or coeliac disease, while of red blood cells, where the parasite is immune cells a balance between pro-death increased regulatory T cell activity can protected or ‘hidden’ from the immune and pro-survival molecules determines suppress the immune system when it system while it grows and replicates. whether they live or die. In this paper it should be actively killing cancerous or In this paper, the authors use the latest is shown that one particular pro-survival infected cells. In this paper the authors super resolution microscopy to define the molecule, Mcl-1, is essential for germinal show that two proteins that regulate gene critical events involved in this process, centre function and that this molecule expression (IRF4 and Blimp-1) sequentially capturing for the first time the malaria might be a good target for therapies to induce the maturation of precursor cells parasite invading a red blood cell. prevent some types of B cell cancers. into particular types of regulatory T cells, paving the way for potential therapies for autoimmune disease and cancer.

34 Walter and Eliza Hall Institute Annual Report 2010-2011 Discovery

Comprehensive, quantitative mapping of Germinal center B and follicular The golden anniversary of the thymus. T cell epitopes in gluten in celiac disease. helper T cells: siblings, cousins or just Miller JFAP. Nature Reviews Immunology. Tye-Din JA, Stewart JA, Dromey JA, good friends? 2011 May 27; 11(7):489-95. Beissbarth T, van Heel DA, Tatham A, Nutt SL, Tarlinton DM. Nature Professor Jacques Miller is famed for Henderson K, Mannering SI, Gianfrani C, Immunology. 2011 Jun; 131(6):472-7. discovering that the thymus, which had Jewell DP, Hill AV, McCluskey J, Rossjohn In this review, the authors describe the no known function at the time, was J, Anderson RP. Science Translational intimate relationship between activated essential for development and maturation Medicine. 2010 Jul 21; 2(41):41-51. B cells and helper T cells, which are of T cells. In this history and timeline, Coeliac disease results from a severe involved in activating other immune Professor Miller recounts the key immune reaction in the gut to peptides cells, in the germinal centres of the discoveries that established our current in wheat, rye and barley. The only spleen. This interaction determines the understanding of the division of the current treatment is strict avoidance of maturation of B cells into antibody- immune system into the B cells, which these grains in the diet. In this paper, producing plasma cells as well as the produce antibodies, and T cells which a comprehensive analysis of every formation of long-lasting memory B cells directly kill infected cells and aid in the possible toxic peptide in gluten revealed that allow a rapid response to subsequent immune response, as well as how they that only three peptides account for infectious organisms. interact with each other. the inflammatory response in people with coeliac disease, paving the way for development of a vaccine against this disease.

Cells of origin in cancer. IL-7 engages multiple mechanisms to interleukin 7 (IL-7) was used to boost Visvader JE. Nature. 2011 Jan 20; overcome chronic viral infection and the immune response in a mouse model 469(7330):314-22. limit organ pathology. of chronic viral disease. Treatment with In this review, Professor Jane Visvader Pellegrini M, Calzascia T, Toe JG, Preston IL-7 was able to resolve the infection and discusses the evidence that cancers arise SP, Lin AE, Elford AR, Shahinian A, Lang limit organ damage by decreasing the from a particular ‘cell of origin’ – a subset PA, Lang KS, Morre M, Assouline B, Lahl levels of SOCS3 (Suppressor of Cytokine of cell type(s) within an organ – through K, Sparwasser T, Tedder TF, Paik JH, Signalling 3), a potent molecule that an initial genetic change, and that DePinho RA, Basta S, Ohashi PS, Mak dampens the immune response. multiple further genetic changes result TW. Cell. 2011 Feb 18; 144(4):601-13. in the mature cancer. It is argued that Chronic viral infections such as Science and Science Translational identifying these ‘cells of origin’ will help HIV and hepatitis B and C overwhelm Medicine journal covers reproduced with to properly classify tumours and improve the immune system in early stages of permission of AAAS. our ability to develop new therapeutic infection, and establish lifelong, persistent Cell and Cell Host and Microbe journal strategies to appropriately treat them. infections. Researchers investigated ways covers reproduced with permission of Elsevier. to boost the immune response to enable Nature and Nature Reviews Immunology the body to clear virus. In this paper, journal covers reprinted by permission from an immune messenger molecule called Macmillan Publishers Ltd.

Annual Report 2010-2011 Walter and Eliza Hall Institute 35 Awards

Staff and students at the institute have been honoured with a number of national and international awards and fellowships this year. These honours included an induction to the Royal Society UK, the Science Minister’s Prize for Life Scientist of the Year and an Australia Fellowship. Honours and awards received by staff at the institute over the past 12 months include:

Internationally-recognised malaria In 2010, institute director Professor Structural biologist Dr Matthew researcher Professor Alan Cowman was Doug Hilton was named a Fellow of the Call was awarded a $150,000 Victorian elected a Fellow of the Royal Society, the Academy of Technological Sciences and Endowment for Science, Knowledge and UK’s peak academy promoting excellence Engineering (ATSE). ATSE promotes the Innovation (VESKI) Fellowship by the in science. Professor Cowman has made development and adoption of existing Victorian Government to continue his major contributions to elucidating the and new technologies to improve and novel studies of immune cell receptors mechanisms used by malaria parasites sustain Australia’s society and economy. and signalling. Dr Call focuses on the to resist some of the most important The academy said Professor Hilton was function and role of the portions of cell antimalarial drugs. This has had elected because he “combines excellence signalling receptors that are embedded implications for the development of new in medical research with personal within cell membranes. His research antimalarial treatments and opened the commitment to clinical translation of has the potential to drive development way for surveillance of the geographic his discoveries”. of a new class of drugs for treating spread of drug-resistant strains of malaria. Institute biochemist Dr Colin Ward autoimmune diseases. Cancer researcher Professor Jane was one of 17 new fellows appointed to Dr Chris Tonkin was named 2011 Visvader received a $4 million Australia the Australian Academy of Science. Dr Victorian Young Tall Poppy of the Year Fellowship from the Australian Ward, from the institute’s Structural by the Australian Institute of Policy and Government to continue her work into Biology division, has spent many Science for his work on parasite biology. the origin of breast, ovarian and lung years studying cell surface receptors The Tall Poppy Campaign celebrates cancers. Professor Visvader was one of including the insulin-like growth factor Australian scientific and intellectual only six scientists awarded the fellowship, receptor, the insulin receptor, and two excellence and encourages younger which supports medical research with members of the epidermal growth factor Australians to follow in the footsteps of the potential to significantly benefit receptor family. outstanding achievers. Dr Justin Boddey Australians. and Dr Erinna Lee were also finalists.

Solving the mystery of platelets and blood cancers

Solving a 50-year-old mystery about “This immediately tells you something The discovery raised the prospect of platelet biology saw Dr Benjamin Kile about why mutations in Erg cause developing new drugs to prolong the awarded a Science Minister’s Prize for cancer,” he said. “Cancers acquire a lot of shelf-life of platelets stored in blood Life Scientist of the Year in 2010. characteristics of stem cells, so the fact banks, increasing the availability of this Dr Kile, from the Cancer and that it is switched on in tumours suddenly life-saving product for cancer patients Haematology division, was presented made sense.” and others in danger of serious blood loss with the award by the Hon. Kim Carr, In 2007, Dr Kile and his institute or clotting disorders. Minister for Innovation, Industry, Science colleagues received international and Research. The prize recognises attention for identifying the molecular outstanding achievement in science that program that controls platelet lifespan, advances, or has the potential to advance, transforming the field and solving a human welfare. 50-year-old mystery about the genes that Dr Kile and his colleagues investigate control whether platelets live or die. cancer, stem cells and blood cell “We discovered that the process is production. His major discoveries include controlled by a pro-survival protein called research into platelets and platelet Bcl-xL and a pro-death protein called lifespan and identification of the normal Bak. The two are in balance in a healthy function of the Erg gene, which is linked platelet, but as it circulates, Bcl-xL slowly to many cancers. runs out, like sand in an hourglass. When Dr Kile said his team showed that the sands runs out, Bak kills the platelet, Erg is a regulator of blood stem cells. triggering its removal from the blood.” Dr Benjamin Kile

36 Walter and Eliza Hall Institute Annual Report 2010-2011 Translation

Associate Professor Clare Scott is searching for new, more effective treatments for ovarian cancer.

Annual Report 2010-2011 Walter and Eliza Hall Institute 37 Translating our research

Translational research continues to move forward at the institute with our strong foundations in basic research being used to transform data and knowledge into meaningful health outcomes through better medical practice. Our expanding disease research areas include: ϐ anti-cancer treatments for breast cancer, ovarian cancer, lung cancer and blood cancers such as leukaemia, lymphoma and multiple myeloma; ϐ treatments for inflammatory diseases such as rheumatoid arthritis and septic shock, and immune disorders including coeliac disease and type 1 diabetes; ϐ new vaccines and drugs to target infectious diseases such as malaria, hepatitis B and C, and HIV; and ϐ personalised medicine, where a patient’s treatment is based on their unique clinical, genetic, genomic and environmental circumstances. The institute encourages, supports and continues to develop clinical collaborations. Fourteen highly skilled clinician-scientists study major diseases and directly link their research findings at the institute to their clinical practice. Through its clinical collaborations, the institute maintains strong links with The Royal Melbourne Hospital, the Royal Women’s Hospital and the Peter MacCallum Cancer Centre, as well as other health facilities throughout Australia and internationally. Our clinician-scientists are also currently involved in more than 80 national and international clinical trials. Many of these trials have achieved significant breakthroughs including a nasal insulin vaccine to treat type 1 diabetes, continued trials and research to support the development of a vaccine for malaria, a new class of anti-cancer drug, and an international phase II trial that has identified a promising Clinical Translation Centre staff new treatment for ovarian cancer. are, from left: Ms Jenni Harris, Ms The institute’s highly anticipated new Clinical Translation Centre was completed Naomi Sprigg, Professor Andrew Roberts and Dr Lina Laskos. at the end of June 2011. It is a central facility that will form the cornerstone Dr Jason Tye-Din (below right) is of translational and clinical research at the institute, providing the essential a clinical researcher, with a joint infrastructure and personnel to expedite the translation of laboratory discoveries appointment at The Royal Melbourne into clinical applications. Hospital, who studies coeliac disease.

38 Walter and Eliza Hall Institute Annual Report 2010-2011 Translation

A Clinical Translation Standing Committee has recently been established with the key goal being identification and removal of barriers to translational research. The committee also provides advice about translational and clinical research to the director and senior management, and assists the head of clinical translation, Professor Andrew Roberts, with the operation of the Clinical Translation Centre. The group also has an essential role in attracting, supporting and retaining medically-qualified researchers at the institute. This year we held our inaugural translational forum. Focusing on leukaemia and lymphoma, this full-day event brought together more than 60 institute researchers and selected expert external clinicians for presentations and discussions about current laboratory research, clinical updates and strategies for future opportunities and development.

Coeliac disease vaccine shows promise in phase I trial

Coeliac disease is a chronic disease the body’s rejection of dietary gluten so Dr Anderson said. “The results of caused by an immune reaction to the patients can resume a normal diet and a population study suggest that a gluten protein found in wheat, rye and return to good health.” combination of blood and genetic testing barley. Up to one per cent of the world’s Nexvax2® is being developed by US could effectively diagnose coeliac disease population is affected by coeliac disease, biotechnology company ImmusanT, of without these painful and invasive tests, which is currently only treatable by which Dr Anderson is chief scientific and and reducing costs by up to 50 per cent, eliminating gluten from the diet. In medical officer. Dr Anderson said the which creates a win-win situation.” people with coeliac disease, immune peptides used as part of the vaccine could cells react to gluten and trigger an also be used to improve diagnostic testing immune response that damages the of coeliac disease. lining of the small intestine and inhibits “Diagnosing coeliac disease can be its ability to absorb nutrients from food. quite costly, requiring invasive tests Dr Bob Anderson heads coeliac Research by Dr Bob Anderson from and biopsies to confirm the disease,” disease research at the institute. the institute’s Immunology division has led to the world’s first potential vaccine for coeliac disease. A worldwide phase I clinical trial has shown promising results and the vaccine is expected to move to phase II trials within the next year. If successful, the vaccine will be suitable for treating approximately 90 per cent of coeliac disease cases. The three peptides in gluten on which the vaccine is based were previously discovered by Dr Anderson as being ‘toxic’ to people with coeliac disease, and form the basis of the coeliac disease vaccine Nexvax2®. “Our phase I study showed that Nexvax2® was safe to use and well tolerated, and importantly, that it had the desired biological response in patients with coeliac disease,” Dr Anderson said. “We expect the vaccine to enter phase II trials by next year, and hope to demonstrate a dramatic reduction in

Annual Report 2010-2011 Walter and Eliza Hall Institute 39 Developing our research

Building strongly on prior activities, the institute’s Business Development Office experienced some major milestones in translating the institute’s research in 2010-11. The number of material transfer agreements rose by more than 20 per cent, to 300 for the year, and 85 commercial and collaboration agreements were entered into, a four per cent increase over the previous year. Major translation outcomes for the institute this year included: ϐ advancing the tripartite collaboration with Genentech, a member of the Roche Group, and Abbott to phase I trials; ϐ teaming up with BD Biosciences for commercialisation of research reagents; ϐ collaborating with Cancer Research Technology Ltd to progress dendritic cell targeting; ϐ progression of the target discovery collaboration with CSL; ϐ completing phase I trials of Nexvax2® for treatment of coeliac disease; ϐ outcomes from Catalyst Fund investments; and ϐ completion of the move to in-house patent prosecution.

Research reagent collaboration that could dramatically enhance the Coeliac disease vaccine completes The institute entered into a immune response in both cancer and phase I trials collaboration with US-based global infectious diseases. Combining the The start-up company Nexpep Pty Ltd medical technology company BD previously competitive approaches to successfully completed a phase I clinical Biosciences, a business segment of BD translation of Clec9A meant that we trial of Nexvax2®, a peptide-based vaccine (NYSE:BDX), to evaluate and develop were able to move quickly to ‘proof- designed to induce tolerance to gluten, the institute’s antibodies for research of-concept’ using an HIV model, thus the protein that causes coeliac disease. and diagnostic use. Antibodies are enhancing the possibility of finding a Nexpep transferred its assets to US-based important research and diagnostic tools development partner. ImmusanT which was specifically created and this collaboration will ensure a CSL collaborations to commercialise the technology through strong focus on making the institute’s access to US capital markets. Basic research tools commercially available. Our strategic translation relationship research headed by Dr Bob Anderson Several antibodies have already been with CSL progressed strongly during the will continue at the institute and a selected for commercialisation. The year with late pre clinical progression new collaborative agreement has been partnership builds on our programs of the G-CSF (granulocyte colony executed with ImmusanT. focused on identifying novel targets stimulating factor) antagonism program for treating inflammatory diseases based for therapeutic monoclonal antibody Dr Julian Clark and drug development, many involving on discoveries in the institute’s Reid development of new antibodies through Laboratory, headed by Professor Ian the institute’s in-house monoclonal Wicks. The collaborative target discovery antibody facility. program based on a systems biology approach to identifying novel drug targets Dendritic cell targeting and Clec9A resulted in the discovery of several new Our agreement with Cancer Research potential drug targets. This program Technology Ltd, the technology transfer was expanded during the year through company of Cancer Research UK, for the successful securing of funds from the cross licensing and commercialisation of CSIRO Science Industry and Endowment Clec9A-related dendritic cell-targeting Fund (SIEF) to carry out a parallel target intellectual property has significantly discovery program in blood stem cells. enhanced our ability to develop a The program aims to develop agents novel vaccine platform for cancers and for stem cell mobilisation and develop infectious diseases. Clec9A is a molecule methods for in vitro platelet production. on the surface of CD8+ dendritic cells

40 Walter and Eliza Hall Institute Annual Report 2010-2011 Translation

Catalyst Fund delivers drugs, a new platform for the production The direct use of foreign attorneys has In its second year of operation, the of antibodies that are extremely difficult provided better access to information Business Development Office Catalyst to produce, particularly for autoimmune on changes to examination procedures, Fund for ‘proof–of-concept’ trials of conditions, and demonstrating that more time to consider office actions and new translation opportunities achieved a soluble cell surface molecule has less requests for an extension of time to returns well in excess of the investment immune regulating properties and is a respond. With a strategy driven by the and has enabled progression of several potential biological agent for therapy of expertise and experience represented promising projects. inflammatory diseases. by the Business Development Office’s Investments included a new class intellectual property group, we develop Patent prosecution of kinase inhibitors for treating solid direct relationships with our attorney tumours, dendritic cell-targeting The first full year’s results from counterparts in key territories. technology for infectious disease and in-house patent prosecution confirm cancer therapy, potential antagonists of the benefits of increased service level, IGF-1R as tool compounds and cancer improved accuracy and reduced expenses.

Institute discovery leads to clinical trials of new cancer drug

Chronic lymphocytic leukaemia (CLL) have begun to receive the agent ABT-199 The head of business development at is the most common type of leukaemia as part of a worldwide phase Ia clinical the institute, Dr Julian Clark, described in Australia. It is a disease of the white trial coordinated locally by Cancer the collaboration with Abbott and blood cells that develops over months Trials Australia. Genentech as unique. “The combination or years, and is most common in Institute director Professor of large biotech and pharmaceutical adults. One in 176 Australians will be Doug Hilton said this collaborative companies with an academic research diagnosed with CLL by the age of 85. arrangement enhanced the institute’s institute is regarded as the industry A scientific discovery made 20 years ability to rapidly translate its laboratory benchmark,” he said. “We anticipate ago at the Walter and Eliza Hall Institute discoveries into benefits for patients. “The that other compounds discovered at the has led to the development of a potential institute has supported research teams institute will be able to enter clinical trials new anti-cancer agent, ABT-199 (GDC- that are dedicated to improving outcomes through similar collaborative efforts.” 0199/RG7601), that is now entering for patients,” he said. “In this case we are Professor David Huang, who heads clinical trials to treat CLL. ABT-199 is seeing more than two decades of research the Chemical Biology division, in a so-called ‘BH3-mimetic’ drug, which culminating in what we hope will be a the institute’s high-throughput is designed to block the function of the promising new drug.” chemical screening facility. protein Bcl-2, making leukaemia cells vulnerable to programmed cell death. The cancer-causing role of Bcl-2 was first discovered at the institute by then- PhD student and current deputy director Professor David Vaux, with Professors Suzanne Cory and Jerry Adams. Bcl-2 is a pro-survival protein, preventing cells from undergoing programmed cell death (apoptosis) after injury. Bcl-2 is over-expressed in a number of cancers, including CLL, and research at the institute over the past two decades has explained much about how Bcl-2 and related molecules function to determine if a cell lives or dies. ABT-199 was co-developed for clinical use by two companies, Abbott and Genentech, and was discovered in a joint research collaboration that also involved scientists at the Walter and Eliza Hall Institute. Patients with CLL

Annual Report 2010-2011 Walter and Eliza Hall Institute 41 Patents granted in 2010-2011

A method of treatment and prophylaxis Inventors: K Lawlor, I Wicks, I Campbell, A Roberts, D Metcalf Australia and Japan A method of diagnosis and treatment and agents useful for same Inventors: J Visvader, G Lindeman, E Sum, L O’Reilly Japan and New Zealand Modified cells that co-express Blimp1 and a reporter molecule and methods of using the same Inventors: A Kallies, J Hasbold, D Tarlinton, L Corcoran, P Hodgkin, S Nutt Australia Alpha-helical mimetics Inventors: G Lessene, J Baell United States Therapeutic agents and uses thereof Inventors: M O’Keefe, K Shortman, B Francke, L Harrison, R Steptoe, D Vremec Europe and New Zealand A method of cell isolation Inventors: G Lindeman, J Visvader, M Shackleton, F Vaillant Australia

Protecting our assets

The second major annual laboratory notebook audit was conducted by the Business Development Office during the year. Compliance with international laboratory notebook standards is essential if the institute is to capture and exploit its intellectual property, and be compliant with the expectations of our translation partners who expect our standards of documentation to be commensurate with our reputation for research. The audit spanned 47 laboratories, included 228 scientists and revealed a significant improvement in compliance, with 41 per cent of scientists’ notebooks being rated as ‘excellent’. During the year 56 per cent of the institute’s laboratories were engaged in collaborative research with industry. Importantly, all laboratories having commercial collaborations had compliant notebooks. Dr Tricia Diggle (far left) and Ms Carmela Laboratory and division heads were given Monger from the Business Development feedback and we look forward to this Office discuss laboratory notebook being an annual event. compliance with Dr Grant Dewson (centre).

42 Walter and Eliza Hall Institute Annual Report 2010-2011 Education

Dr Guillaume Lessene (above left) and Honours student Mr Michael Roy, from the Chemical Biology division.

Annual Report 2010-2011 Walter and Eliza Hall Institute 43 Education

The Education Committee is reflecting on a productive and rewarding year, which derives from the pleasure of working with bright young people and seeing them grow as individuals and as scientists.

The institute currently has 80 PhD the role of proteins that remodel red in The University of Melbourne’s students and 15 Honours students and blood cells after malaria invasion. Department of Biochemistry. has hosted 20 Undergraduate Research This year’s Harold Mitchell In return, Department of Biochemistry Opportunities Program (UROP) Foundation travel awards went Honours students participated in the students, 18 overseas research trainees to PhD student Sarah Oracki and institute’s Experimental Design and and nine vacation students over the postdoctoral scientist Luke Pase. Statistics course. The mutual teaching past 12 months. Ten PhD students Ms Oracki used her fellowship arrangements have broadened and completed their degree in the past year. to attend the 5th International enriched the experiences of students in Our congratulations go to Drs Ryan Conference on Gene Regulation in both departments, with early feedback Brady, Duncan Carradice, Carolyn de Lymphocyte Development as well as suggesting the new coursework was a Graaf, Shirley Elkassaby, Sarah Kinkel, visit laboratories in London, Boston success and a challenge to the students. Hiu Kiu, Catherine Nie, Sarah Oracki, and New York. Dr Pase used his One of our explicit aims is to Jonathan Richards and Hua Yu on fellowship to attend the European encourage medical professionals this achievement. Molecular Biology Organization to participate in laboratory-based We were fortunate to have an (EMBO) Conference on Molecular research, as clinician-scientists form exceptional group of Honours students and Cellular Basis of Regeneration and an important link for knowledge in 2010. All 21 students of the 2010 Tissue Repair as well as visit several translation between basic science and Honours cohort achieved first-class leading European institutes to explore clinical care. Our recent initiatives in honours. Congratulations go to our postdoctoral opportunities. this area include the establishment of a top 2010 Honours student, Ms Hannah A major task in the past year small scholarship for medical students Vanyai, for being named on the Dean’s has been planning new Honours who interrupt their studies briefly to Honour List for the Faculty of Science. coursework. As a consequence, our 2011 engage in laboratory-based research Congratulations also to Alan Yap, Honours students enjoyed the benefit at the institute. A second development who was the successful recipient of the of a new Experimental Design and is an internal PhD scholarship to Cyril and Paddy Pearl Scholarship. This Statistics course taught by Professor accommodate exceptional candidates PhD scholarship was established in 2010 Terry Speed and colleagues from the who are medical graduates and by the late Mrs Paddy Pearl in memory Bioinformatics division, as well as passionate about laboratory research. of her late husband, Cyril. Alan is Professor David Vaux and Dr Anne undertaking his PhD in the Infection Voss. The students also undertook PhD students Maya Olshina and Immunity division, investigating a quarter of advanced coursework (left) and Alex Delbridge

44 Walter and Eliza Hall Institute Annual Report 2010-2011 Education

Malaria parasite caught red-handed invading blood cells

Each year the malaria-causing never been seen before,” said Mr Riglar. More information: Riglar DT, Richard Plasmodium parasite infects more than “There are many proteins that we know D, Wilson DW, Boyle MJ, Dekiwadia C, 400 million people worldwide, and are involved in the invasion process, but Turnbull L, Angrisano F, Marapana DS, as many as a million people, mostly we don’t know precisely where they are Rogers KL, Whitchurch CB, Beeson JG, children, die from malaria. positioned, or how they act. Now we can Cowman AF, Ralph SA, Baum J. Super- Mr David Riglar, a PhD student working start to answer some of these questions, resolution dissection of coordinated with Dr Jake Baum in the Infection and which will be really exciting for malaria events during malaria parasite invasion Immunity division, has for the first time researchers worldwide. of the human erythrocyte. Cell Host captured images of malaria parasites in the “Being able to clearly see each Microbe. 2011 Jan 20; 9(1):9-20. act of invading red blood cells. separate stage of invasion with this level The malaria parasite is only one micron of detail will also help us to precisely (one millionth of a metre) in diameter, determine how antimalarial drugs and in the past it has been difficult both or vaccines stop the parasite from to infect red blood cells with the parasite entering the red blood cell. In the future, in the laboratory, and to capture images new treatments for malaria may be of this process. designed to stop particular stages of the Mr Riglar and colleagues developed invasion process,” he said. new ways to study parasites during the invasion process. They collaborated with Collaborating institution: researchers from the ithree institute at ithree institute, the University of the University of Technology, Sydney, to Technology, Sydney. reliably capture high-resolution images of the parasite at each and every stage Funding partners: National Health and of invasion. This was achieved using a Medical Research Council, The University combination of electron, light and super resolution microscopy – a technology of Melbourne (Pratt Foundation platform new to Australia. Scholarship), Canadian Institutes of “These innovative imaging techniques Health, University of Technology, Sydney, have allowed us to observe the invasion Australian Research Council and the PhD student Mr David Riglar process at a molecular level that has Victorian Government.

Uncovering the molecular control of airway development

The development of a mammal requires structures in the head, neck and chest. every organ and structure to be “We found that the size of the upper formed in the correct location within airways, especially the nasal passage, the embryo. This process is precisely requires the correct expression of Moz in controlled by the actions of thousands a particular region of the early embryo of genes. called the neural crest,” she said. Genetic defects that hinder proper “This is the first time that a single gene embryonic development are seen in has been linked to the control of airway human conditions such as DiGeorge size. We can now begin to understand the Syndrome, in which blood vessels and molecular machinery that drives airway organs in the head, neck and upper chest development.” cavity are not correctly formed. Ms Vanyai was the top Honours The control of embryonic development student in The University of Melbourne by the Moz gene was the focus of Ms Department of Medical Biology in 2010, Hannah Vanyai’s Honours research in the and was named on the Dean’s Honour Molecular Medicine division, supervised List for the Faculty of Science. As a PhD by Drs Anne Voss and Tim Thomas. student at the institute, Ms Vanyai is Ms Vanyai’s project examined whether continuing to define how Moz regulates MOZ controls the development of airway development. Honours student Ms Hannah Vanyai

Annual Report 2010-2011 Walter and Eliza Hall Institute 45 2010-2011 graduates

The following students successfully completed their studies in the past year:

Doctor of Philosophy, Bachelor of Science (Honours), The University of Melbourne The University of Melbourne

Dr Ryan Brady Natasha Anstee Lewis Murray Benzoylureas as BH3-only peptide The impact of Bcl-2 versus Mcl-1 Role of natural killer receptors in the mimetics: design, synthesis and overexpression in haemopoietic cells. control of malaria pathogenesis. conformational constraints. Supervisors: Dr K Campbell, Supervisors: Dr D Hansen and Dr L Schofield Supervisors: Dr J Baell, Dr G Lessene and Dr C Vandenberg and Professor S Cory Blazhe Nedanovski Professor R Norton Fiona Bell Reversing the drug resistance observed Dr Duncan Carradice Monitoring Bak and Bax activation and oligomerisation in live cells. in mouse lymphomas which overexpress Genetic basis of congenital myeloid failure Polycomb genes. syndromes in mutant zebrafish. Supervisors: Dr R Kluck and Dr G Dewson Supervisors: Dr C Scott and Dr M Wakefield Supervisors: Dr G Lieschke and Dr J Layton Bianca Capaldo Victoria Ryg-Cornejo Dr Carolyn de Graaf Definition of transcriptional regulators of commitment and differentiation of Role of T cell homing in the control of Genomic analyses of haemopoiesis. mammary progenitor cells. pathogenesis and immunity to malaria. Supervisors: Professor D Hilton, Dr G Smyth Supervisors: Professor J Visvader and Supervisors: Dr D Hansen and Dr L Schofield and Dr L Wu Professor G Lindeman Lisa Sampurno Dr Shirley Elkassaby Shih Chieh Chang Programmed cell death and angiogenesis. Effects of vitamin D on immune and Novel potassium channel blockers for the metabolic function in humans. treatment of autoimmune diseases. Supervisors: Dr L Coultas and Supervisors: Professor L Harrison, Supervisors: Professor R Norton and Professor A Strasser Dr S Fourlanos and Dr J Dromey Dr C Galea Joanne Slater Dr Sarah Kinkel Kelan Chen Function of BCL2 family proteins in Regulation of promiscuous expression in Structure-function analysis of the epigenetic zebrafish. medullary thymic epithelial cells. regulator protein, SmcHD1. Supervisors: Dr G Lieschke and Dr L Pase Supervisors: Dr M Blewitt, Dr W Heath, Supervisors: Dr J Murphy and Dr M Blewitt Hannah Vanyai Dr H Scott and Professor D Hilton Monica Diviak The role of the monocytic leukaemia Dr Hiu Kiu How does apoptosis regulate autoimmune zinc finger protein (Moz) in embryonic mediated tissue inflammation? The role of SOCS3 and related proteins in development. inflammatory processes. Supervisors: Professor I Wicks and Dr K Lawlor Supervisors: Dr A Voss and Dr T Thomas Supervisors: Professor A Roberts and Professor W Alexander Freya Kahn Hong Juan Wu Calcium regulation in Toxoplasma gondii Dr Catherine Nie Targeting apoptosis for treating cancer. Supervisors: Professor D Huang and host cell invasion. Leukocyte trafficking in the control of Professor A Roberts Supervisors: Dr C Tonkin and disease and immunity to malaria. Professor A Cowman Supervisors: Dr D Hansen and Dr L Schofield Anastasia Kurniawan Inflammatory mediators of insulin Alan Yap Dr Sarah Oracki resistance in human obesity. Role of T cells and the spleen in the Resolving causes and consequences in a Supervisors: Dr J Wentworth and aetiology of severe malarial anaemia. model of autoimmune disease. Professor L Harrison Supervisors: Dr D Tarlinton and Dr S Nutt Supervisors: Dr L Schofield and Dr D Hansen Stephen Ma Janet Yeo Dr Jonathan Richards Elucidating the Bak apoptotic pore complex. The role of antibodies to merozoite Supervisors: Dr R Kluck and Dr G Dewson Transcriptional regulation of immune cells antigens in protection from symptomatic of the gut. Plasmodium falciparum infection. Julia Marchingo Supervisors: Dr G Belz and Dr S Nutt Supervisors: Dr J Beeson and The effect of co-stimulation on T-cell Elizabeth Zuccala Professor G Brown dynamics. Supervisors: Professor P Hodgkin and Cell-cell interactions during malaria Dr Hua Yu Dr S Heinzel parasite invasion of the human erythrocyte. Investigation of autoreactive T cells in type James McCoy Supervisors: Dr J Baum and 1 diabetes. Functional characterisation of calcium- Professor A Cowman Supervisors: Professor L Harrison, dependent protein kinases in Toxoplasma Dr S Mannering and Dr A Lew host cell invasion. Supervisors: Dr C Tonkin and Dr J Baum

46 Walter and Eliza Hall Institute Annual Report 2010-2011 Education

Seminars

The Wednesday seminar series provides a forum for the best research at the institute to be showcased before the entire scientific staff while also providing a platform for visiting researchers to present their work. This year we hosted 40 seminars in the Wednesday series, which included five guest speakers in addition to representatives from all of the institute’s divisions, at all career levels. We also had eight PhD students present at the Wednesday forum. A slight change to the format this year was the inclusion of a number of laboratory heads giving overviews of their recent achievements and plans for the near future. One of the institute’s newest laboratory heads, Dr Marie-Liesse Asselin-Labat from the Stem Cells and Cancer division, presented her work on the breast cancer stem cell, an area of great current interest. From our more senior ranks Professor Jerry Adams, who is joint head of the Molecular Genetics of Cancer division, gave an overview of the molecular causes of cancer, highlighting how the work into apoptosis from his division over many years has facilitated the development and testing of potent novel anti-cancer therapies. Among our guests, we were fortunate to host Professor Meinrad Busslinger from the Research Institute of Molecular Pathology, Vienna, Austria. Professor Busslinger is a member of the institute’s Scientific Advisory Board and presented an outstanding talk describing his long, successful and technically sophisticated analysis of lymphocyte development. We also had former institute students return to present talks about their current research. This included Dr Shalin Naik, now at the Netherlands Cancer Institute, who presented a most exciting insight from his work on a sophisticated approach, Institute board member Dr Graham called bar-coding, that tracks cell differentiation in complex systems. Dr Naik is Mitchell addressing attendees at the function held to celebrate the using this approach to track the development of white blood cells. 50th anniversary of the discovery A full list of institute seminars held in 2010-11 are on the accompanying CD. of the function of the thymus.

Annual Report 2010-2011 Walter and Eliza Hall Institute 47 Institute awards

The Burnet Prize

Dr Marie-Liesse Asselin-Labat from Dr Asselin-Labat received the award In 2011, Dr Asselin-Labat was selected the Stem Cells and Cancer division was for her studies of breast stem cells and to establish her own laboratory within awarded the Burnet Prize in 2010, the their role in some types of breast cancer. the Stem Cells and Cancer division. Her institute’s top award. She discovered that breast stem cells laboratory will focus on lung cancer and The prize has been awarded annually are exquisitely sensitive to the female the cells that lead to the development of since 1987 and was established hormones oestrogen and progesterone. lung cancer. through a bequest from Sir Macfarlane The finding explains decades of evidence “I’m interested in looking at how lung Burnet (institute director 1944-65). It linking breast cancer risk to exposure to stem cells are regulated and what drives acknowledges exceptional achievement by female hormones, and opens the way for tumour initiation in the lungs,” she said. early-career researchers. the development of new preventions and “There is a real need for research into treatments for breast cancer. lung cancer.” The de Burgh Fellowship

This year the institute established the Metcalf, Professor Jacques Miller and focus is cancer research and Dr Lessene de Burgh Fellowship to honour the Sir Gustav Nossal obtained their first is currently working on developing role Professor Patrick de Burgh played taste of research. inhibitors to the pro-survival Bcl-2 in shaping the institute. Professor Dr Guillaume Lessene from the proteins that are involved in programmed de Burgh was an infectious disease institute’s Chemical Biology division cell death, for treatment of several types researcher. He died at the age of 94 was the inaugural recipient of the de of cancer. He is also involved in projects on 1 August 2010. Burgh Fellowship. looking at other cancer targets, such It was in Professor de Burgh’s Dr Lessene translates research findings as tyrosine kinases, and non-cancer laboratory at the University of Sydney from the institute into the discovery and targets involved in conditions such as that institute legends Professor Donald development of new drugs. His main Alzheimer’s disease.

Dr Marie-Liesse Asselin-Labat Dr Guillaume Lessene Dr Brian Smith’s ‘Molecular Plaid’

The institute’s other award winners were: Best seminar: The 2010 Seminar Wentworth from the Autoimmunity Three awards were given for 25 years Prize was a three-way tie between Dr and Transplantation division for his service to the institute: Ms Heather Justin Boddey from the Infection and presentation ‘Inflammation in diabetes: Orange and Ms Josie Pink from Immunity division for his presentation cause or consequence?’. Preparation Services, and Mr David ‘Export of malarial virulence proteins Art in Science Prize: Dr Brian Smith Vremec from the Immunology division. that remodel parasitised human from the Structural Biology division was erythrocytes’, Dr Stefan Glaser awarded the Art in Science Prize for his from the Cancer and Haematology image ‘Molecular Plaid’, a striking image division for his presentation ‘Role of that shows the dynamics of molecules pro-survival Bcl-2 family members in of water. acute myeloid leukaemia’, and Dr John

48 Walter and Eliza Hall Institute Annual Report 2010-2011 Engagement

Students from Ivanhoe Girls’ Grammar School on a discovery tour at the institute’s Bundoora campus.

Annual Report 2010-2011 Walter and Eliza Hall Institute 49 Engagement

One of the key goals of the institute is to drive community conversations about science and the benefits of medical research for public health and wellbeing. We strongly believe that fostering an cancers and the latest developments people nationally and internationally, open dialogue about Australian research in treatment, while in March 2011 and keep up-to-date on the latest news and innovation will help advance Dr Marc Pellegrini spoke on the in the sector as well as engage with debates into the 21st century on the topical issue of infectious disease and our supporters. future of science and medical research. antibiotic-resistant bacteria. More than A major highlight of the first half of Institute staff and students have 300 people attended these lectures. 2011 was the institute-led Discoveries embraced the opportunity to share The institute was also represented at Need Dollars campaign. The campaign their interest in science. This has The University of Melbourne Festival was instigated by the institute following ranged from participating in the of Ideas, a biennial public lecture reports that the federal government activities of science and biotechnology program intended to stimulate and planned to significantly cut medical organisations, to joining grant review inform community discussions. The research funding in the federal panels, and serving on the boards and theme for the 2011 Festival of Ideas was budget. We were overwhelmed by the committees of organisations across the ‘The Pursuit of Identity: Landscape, community support for the campaign, medical research sector. Our public History and Genetics’. Institute director which attracted an enormous amount engagement has stretched beyond this, Professor Doug Hilton spoke as part of interest and action from not only with institute staff and students sharing of the session ‘The Genetic Revolution: scientists but also community members their knowledge and time with schools, Health and Human Identity’, chaired who were concerned about the potential community groups, donors, bequestors by former institute director Professor outcomes of funding cuts for finding and the wider community to keep them Suzanne Cory. cures and treatments for disease. informed of the latest institute research In the past 12 months the institute The campaign was successful, with and achievements. has joined the social media revolution, the budget being maintained and a This year, we had a large increase establishing a presence on Facebook, review of the medical research sector in discovery tours on offer to the LinkedIn and Twitter. Institute director being announced. public, with 700 people across 30 Professor Doug Hilton also joined groups attending. the conversation on Twitter – follow Researchers and the community Two public lectures were also held: @WEHI_Director for his updates. rally for research in Melbourne as in December 2010 Professor Andrew These social media sites have given us part of the institute-led Discoveries Roberts shared his knowledge on blood a unique opportunity to connect with Need Dollars campaign.

50 Walter and Eliza Hall Institute Annual Report 2010-2011 Engagement

Strategic partners

Collaborative research partnerships are at the heart of much of the research carried out at the institute. We place a high priority on research collaborations that support the institute’s mission of ‘Mastery of Disease Through Discovery’. Many of our collaborations help to The Victorian Cancer Biobank forms of hearing loss. This work aims ensure that fundamental discoveries has also been a major contributor to to develop better diagnostic tools and made in the laboratory are translated the Stem Cells and Cancer division’s to identify molecules that may be to the clinic. The Walter and Eliza Hall research, providing human breast targeted by drugs for the prevention Institute has been involved in a number tumour tissue that enables our and treatment of hearing loss. A of initiatives to drive collaboration in researchers to make new discoveries genome-wide screen for mutations medical research in Australia. about the biology of breast cancers. causing progressive hearing loss in The Victorian Breast Cancer In 2011, the collaboration led to mice has yielded 18 new genetic models Research Consortium, established the discovery by Professors Geoff of this condition. The hearing group in 1997, is a consortium of eight Lindeman and Jane Visvader that a new is also investigating the regulation of Melbourne medical research institutes class of anti-cancer agents called BH3- cell death in the auditory system as a and the Cancer Council Victoria. It is a mimetics show promise for treating potential avenue for intervening in the major funding source for the activities breast cancers that over-express the disease. Understanding the complex of the institute’s Stem Cells and pro-survival Bcl-2 protein, including molecular events that contribute to Cancer division, and was responsible cancers with poor prognosis. onset and progression of cochlear for the long-term funding that aided As a supporting member of the degeneration will help us to design in the discovery of breast stem cells, Hearing Cooperative Research Centre, targeted therapeutic and preventive which are believed to play a role in the the institute is working to better strategies for hearing impairment. development of breast cancer. understand age-related and acquired

Medical Research Commercialisation Fund

The Medical Research development of candidate compounds for to develop first-hand experience with Commercialisation Fund (MRCF), the treatment of Alzheimer’s disease. investment management and venture founded in 2007, provides funding to Alzheimer’s disease is the most capital processes. Dr James Dromey from its member institutes for the early-stage common form of dementia in the elderly, the Business Development Office was development of medical technologies affecting more than 18 million people the first institute staff member to take with commercialisation potential. These globally. Although some therapies exist part in this program, completing it in include the discovery of drug compounds to ease the symptoms, there is no current August 2010. and proof-of-principle projects. treatment to treat the disease or stop The Walter and Eliza Hall Institute has disease progression. been a member of the MRCF since 2007. Dr Brian Smith from the institute’s The MRCF was established through Structural Biology division identified collaboration between medical research two compounds that bind the enzyme institutes and allied research hospitals beta secretase (also called BACE-1), across Australia. The collaborative fund which is elevated in parts of the brain of is supported by the state governments of Alzheimer’s patients. The observation Victoria, New South Wales, Queensland of elevated beta secretase in Alzheimer’s and Western Australia. It currently has was initially made by Dr Genevieve Evin 27 members. from The University of Melbourne and, In 2010 BACE Therapeutics, a company working collaboratively, Drs Smith and formed by the Walter and Eliza Hall Evin have shown the two compounds Institute, The University of Melbourne, are effective in blocking the activity of Mental Health Research Institute and beta secretase potentially slowing or even SYNthesis Med Chem, successfully blocking the progression of Alzheimer’s. Dr James Dromey from the secured $650,000 in funding from the As part of its capacity-building goal, institute’s Business Development MRCF with the support of the Victorian MRCF runs a trainee/secondment Office participated in the MRCF Government to implement the preclinical program for staff of member institutes trainee/secondment program.

Annual Report 2010-2011 Walter and Eliza Hall Institute 51 Scientific and medical community

In addition to their research workloads, our scientists contribute to the scientific and medical community in a variety of ways, both nationally and internationally. This includes serving on review panels, boards and committees, undertaking editorial work for scientific and medical journals, conference organisation and attendance, and involvement with biotechnology and clinical advisory groups and public health programs. This year, our scientists undertook engagement with the medical and scientific communities in the following ways: Institute scientists served on the boards and committees of organisations including the European Molecular Biology Organization, Pasteur Institute (France), Wellcome Trust Sanger Institute (UK), Wellcome Trust Centre for Human Genetics (UK), Cambridge Research Institute (UK), and National Institutes of Health TrialNet (US). Faculty members assisted in evaluating research grants and participated in grant review panels for the National Health and Medical Research Council, Australian Research Council, Cancer Council Australia, National Institutes of Health (US), Cancer Research UK, Juvenile Diabetes Research Foundation (Australia), Wellcome Trust (UK), Pfizer Australia, European Research Council, Canadian Foundation for Innovation, Swiss National Research Council and Medical Research Council (UK). Our researchers have also sat on editorial boards for international science journals such as Proceedings of the National Academy of Sciences of the USA, Journal of Immunology, Cancer Research, International Journal of Haematology, Cell Stem Cell, Cell Death & Differentiation and Oncogene. Our staff have engaged with the biotechnology industry as advisers, consultants and committee members for organisations including the Bio21 Cluster, Cancer Council Victoria, CSL Ltd, GlaxoSmithKline Biologicals, ImmusanT Inc, Malaria Vaccine Initiative of PATH/ MVI, National Breast Cancer Foundation, Victorian Breast Cancer Research Consortium and the Victorian Cancer Agency. More details on our engagement with the scientific community is on the accompanying CD.

Institute hosts government grants announcement

The institute hosted some of Australia’s Federal Minister for Mental Health and University, Children’s Cancer Institute leading scientists in March when the Ageing the Hon. Mark Butler MP, and Australia, National Stroke Research National Health and Medical Research NHMRC chief executive officer Professor Institute, Queensland Institute of Medical Council (NHMRC) chose the institute as Warwick Anderson attended the event, Research and The University of Sydney. the site for its annual announcement of to announce $107 million in funding for The NHMRC program grants scheme program grant funding. nine high-calibre, collaborative projects provides support for teams of high- designed to improve health and wellbeing calibre, internationally-competitive in Australia. researchers who pursue broad, The institute received $38.4 million in collaborative research. funding as part of the announcement. Institute director Professor Doug The funding will support collaborative Hilton said the NHMRC’s program studies that will extend current institute grants scheme provided vital support for research into blood cells and cancer. Australian researchers to tackle complex Division heads Professor Nick Nicola but important research questions that from the Cancer and Haematology might take many years to unravel. division and Professor Jerry Adams from “The program grants scheme is the Molecular Genetics of Cancer division recognition that if Australian scientists are leading the two funded programs. are to continue to make discoveries Several other representatives from the that benefit human health they require Department of Health and Ageing and sustained and significant support that The Hon. Mark Butler MP visiting NHMRC committee attended the event, as brings together large research teams the institute to announce $107 well as grant recipients from The University from diverse areas of medical research,” million in NHMRC funding. of Melbourne, Australian National Professor Hilton said.

52 Walter and Eliza Hall Institute Annual Report 2010-2011 Engagement

Continuing links with the World Health Organization

The World Health Organization (WHO) two months at the institute to learn critical aspect of ensuring that research has renewed the institute’s status as flow cytometric techniques, and in 2011 conducted at the institute is maximally a WHO Collaborating Centre for Ms Elisheba Malau, also from PNGIMR, relevant to improving the treatment and Research and Training in Immunology undertook Honours research at the prevention of this disease,” he said. and Molecular Parasitology until 2014. institute, supervised by Drs Ivo Mueller Professor Alan Cowman, who heads the and Alyssa Barry in the Infection and centre, said it is an important extension of Immunity division. the institute’s malaria research program. The WHO collaboration also “Our collaboration with WHO will supported the attendance of several enhance the development of new vaccines PNGIMR researchers at the International to prevent malaria, a disease that kills Congress of Parasitology in 2010, and more than one million people every year, enabled institute researchers to conduct most of whom live in developing countries. a biostatistics course at the PNGIMR One important aspect is that it assists our in 2011. scientists in accessing valuable malaria Professor Mueller, who taught at the patient samples from malaria-endemic biostatistics course, said the institute’s countries,” Professor Cowman said. WHO Collaborating Centre status The collaboration also enables the was especially important for training Course instructors Professor Ivo institute to train researchers and researchers and building capacity in our Mueller (Infection and Immunity division, front left) and Katie Benton (Stanford field workers from malaria-endemic malaria-endemic partner countries - University, back left) with participants countries. In 2010 Mr Jack Taraika Papua New Guinea, the Solomon Islands in the biostatistics course held at the from the Papua New Guinea Institute and South-East Asia. “Building links with Papua New Guinea Institute of Medical of Medical Research (PNGIMR) spent scientists in malaria-endemic areas is a Research. (Photo credit: Katie Benton)

Quintuple anniversary celebrates science legends

On Thursday 2 June 2011, the Walter discoveries in the field of immunology at first; little did I realise that he had and Eliza Hall Institute hosted more during their time at the institute. In 1958, climbed onto a huge wave that was just than 200 alumni and invited guests Sir Gustav identified that one immune about to break, propelling us younger from around the world to celebrate a cell was only able to produce one type workers into a glorious future,” he said. quintuple anniversary of science legends. of antibody. In the 1950s and 1960s The quintuple anniversary celebration Professor Mackay led the field of research recognised the 50th anniversary of the into autoimmune diseases, coining the discovery of the function of the thymus term ‘autoimmunity’. by institute researcher Professor Jacques The event commemorated more than The four legends, (from left) Dr Margaret Miller. It also honoured four alumni 140 years of service to the institute by Holmes, Sir Gustav Nossal, Professor from the institute who were celebrating Professors Miller and Mackay, Sir Gustav Jacques Miller and Professor Ian Mackay. significant birthdays: Sir Gustav and Dr Holmes. Nossal and Professor Jacques Miller, Their achievements were celebrated who celebrated their 80th birthdays; by former colleagues including Professor and Professor Ian Mackay and Dr Michael Good, Professor Sir Marc Margaret Holmes, who celebrated their Feldmann, Dr Graham Mitchell and 90th birthdays. Professor Mathew Vadas. The thymus was the last organ to have Sir Gustav, director of the institute its function explained. Professor Miller from 1965 until his retirement in 1996, made the discovery whilst working at the reflected that his more than 30 years at Chester Beatty Research Institute and the institute got off to a ‘bad start’. “I had published his landmark study on “the come to work under the world’s greatest immunological function of the thymus” virologist, Sir Macfarlane Burnet, and in The Lancet in 1961. to my dismay he was phasing out virus Sir Gustav, Professor Miller and work, turning the institute almost entirely Professor Mackay all made seminal towards immunology. I was disappointed

Annual Report 2010-2011 Walter and Eliza Hall Institute 53 Public engagement

The institute’s public engagement program has seen many hundreds of people visit the institute this year. Hundreds more have been visited by institute scientists as they take part in external programs such as CSIRO’s Scientists in Schools (see page 57). Public lectures are one way the community can find out about work that is happening at the institute. Two public lectures were held at the institute this year, with more than 300 attendees. In December 2010, Professor Andrew Roberts shared his knowledge on blood cancers and the latest developments in treatments, while the topical issue of infectious disease and antibiotic-resistant bacteria was discussed at a panel on ‘microbial wars’ in March 2011. The information shared during our discovery tours (see page 56) and public lectures is complemented by the work of the institute’s biomedical animation studio, WEHI.TV. WEHI.TV continues to be a valued resource internationally for people seeking accurate scientific visualisations of biological systems and processes (see highlight, below). This year, in addition to the work of WEHI.TV, we produced a short movie to illustrate the research and mission of the institute. The movie gained a wider audience when Qantas Airways made it part of its in-flight entertainment. The movie can be viewed on our website or YouTube channel. The past 12 months have seen a continuation of the marked increase in media coverage on research and other activities at the institute. Several research highlights from the institute received a large amount of newspaper, TV and radio coverage including research on breast cancer, HIV, malaria, coeliac disease, type 1 diabetes and ovarian cancer. Institute scientists are increasingly being sought to provide commentary on important issues in scientific research, policy and communication.

WEHI.TV

The institute’s biomedical animation This year, Mr Berry was recognised States citizens of any age, working in any studio, WEHI.TV, continues to be a for his remarkable achievements and field, who “show exceptional merit and valued resource internationally for vivid, fascinating animations by being promise for continued and enhanced people seeking accurate scientific named one of 23 recipients of the 2010 creativework”. visualisations of biological systems MacArthur Fellowship. Nicknamed and processes. the ‘Genius Award’, the Fellowship is A still from WEHI.TV’s animation We continue to receive a large number a prominent prize awarded to United Breast Stem Cells. of requests for the animations from media, science institutions, schools and students who use the videos as educational and entertainment resources. Visits to the WEHI.TV YouTube channel, WEHImovies, have risen 53 per cent in the past year. This year, biomedical animators Mr Drew Berry and Ms Etsuko Uno created three new animations. The animations, Breast Stem Cells, Control of Breast Stem Cells and Origins of Breast Cancer depict the latest research from the institute’s Stem Cells and Cancer division, and give an overview of the mammary gland, how breast stem cells are influenced by and respond to female hormones, and the role breast stem cells play in the development of some breast cancers.

54 Walter and Eliza Hall Institute Annual Report 2010-2011 Engagement

Discoveries Need Dollars: protecting medical research

In 2011 medical researchers from Health and Ageing and myriad local budget, announced a review of the around the country, along with members of parliament and senators; medical research sector following the colleagues in the health care sector t
more than 12,000 signatures on a campaign. Institute staff have coordinated and many members of the Australian petition tabled in parliament by the the submission of comments from the community, united under the Federal Member for Melbourne Mr Discoveries Need Dollars community on Discoveries Need Dollars campaign Adam Bandt; the terms of reference. banner and fought successfully to t
more than 235,000 visits to the The institute’s management is preserve National Health and Medical Discoveries Need Dollars website, plus optimistic that this review will deliver a Research Council (NHMRC) funding strong support for the campaign’s social more efficient, better resourced medical from cuts in the 2011–12 federal budget. media presence on Twitter, Facebook research enterprise that reflects the The prospect of funding cuts and LinkedIn; passion and verve of our researchers. was undeniable. The message from t
letters from Nobel Prize winners, We are continuing to work with the government was that to bring the budget Australians of the Year, former organisations and individuals that back into surplus every dollar of spending Premiers and other eminent members supported the Discoveries Need Dollars was being examined and no area was to of the community; campaign to ensure that support for be quarantined. Many feared government t
support from medical research bodies, medical research remains a priority area sentiment was that the community did not individual medical research institutes, for state and federal governments, and for care about medical research. universities and hospitals, patient thethe broaderbroader communcommunity.ity. The institute initiated the Discoveries groups; and, most importantly, Need Dollars campaign as a voice for t
myriad heartbreaking and inspiring supporters of medical research. The stories about ordinary Australians community responded with: battling devastating disease who have t
more than 12,000 people attending benefited from medical research, eitherr Rallies for Research in five states in because of improved care or because it April, including 4500 in Melbourne provides hope. (see below); Minister for Mental Health and Ageing t
more than 15,000 letters and postcards the Hon. Mark Butler MP, who has to the Prime Minister, Treasurer, responsibility for the NHMRC and The postcards distributed during the Health Minister, Minister for Mental stewardship of the medical research Discoveries Need Dollars campaign.

Melbourne rallies for research

Supporters of medical research came Evans, a researcher from the institute’s out in force on the lawns of the State Infection and Immunity division, in her Library of Victoria on 12th April 2011 to pleas for the government to save medical protest the government’s proposed cuts research from cuts to the federal budget. to NHMRC funding. Federal Member for Melbourne Mr Adam More than 4500 people attended the Bandt addressed the rally, as did three rally, including staff from all major members of the public who were deeply medical research centres in Melbourne concerned about the planned cuts: Ms and members of the wider community, Nerissa Mapes, who is an ambassador for, many of whom were concerned about the and is affected by, Parkinson’s disease; Mr impact of research cuts on their families’ Sean Lusk, who has cystic fibrosis; and future health. Ms Linda Rodger, who has lost family Hundreds of institute staff, many members to motor neurone disease. wearing white lab coats, carried signs with The Melbourne Rally for Research was slogans such as ‘SOS: Save our Science’ and an astounding success, and together with Federal Member for Melbourne Mr ‘Survivors not Surplus’. rallies in seven other Australian cities, sent Adam Bandt (above right) with institute Protestors chanted ‘Cures Not Cuts’ a strong message to the government about researchers Professor Len Harrison and ‘Research Saves Lives’ as they waved the high level of community support for (above left) and Dr Margo Honeyman banners and cheered MC Dr Krystal medical research. at the Melbourne Rally for Research.

Annual Report 2010-2011 Walter and Eliza Hall Institute 55 Governor-General visits

In December 2010, the Walter and Eliza overview of her studies into epigenetics, to be answered if we are to truly bring Hall Institute was proud to host a visit a relatively new field of research that health benefits to patients.” by Her Excellency, the Governor-General seeks to reveal how gene expression is Ms Quentin Bryce AC. controlled. Her presentation was followed The Governor-General has a by Dr Erinna Lee discussing how studies longstanding interest in medical research, of programmed cell death could lead to which was enhanced when, in June 2010, new cancer treatments and Dr Samantha she led an official delegation to Shanghai, Oakes outlining her research into breast China, that included institute scientist Dr development and how it improves Erika Cretney. understanding of breast cancer and Dr Cretney and Her Excellency both its treatment. appear in the documentary Sisters which Institute director Professor Doug screened at the Australian Pavilion Hilton said it was an honour to host the at the World Expo in Shanghai. The Governor-General at the institute. documentary showcases the achievements “The Governor-General has made of 21 women from Australia and China. clear her interest in medical research and During her visit to the institute the its potential to improve human health,” Governor-General was briefed on recent Professor Hilton said. “We were thrilled discoveries at the institute into breast that she chose to visit our institute to gain cancer, programmed cell death and a better understanding of how we are Institute director Professor Doug Hilton (above epigenetics. Dr Marnie Blewitt gave an tackling the research questions that need left) and Her Excellency Ms Quentin Bryce AC.

Creating conversations about science

Researchers from the Walter and discovered to be the environmental cause Eliza Hall Institute are committed coeliac disease. to discussing and reporting on their “In the years since, the holy grail in scientific discoveries to encourage coeliac disease research has been to greater understanding of science and the identify the toxic peptide components of scientific process. gluten; and that’s what we’ve done,” Dr In July 2010, coeliac disease researcher Anderson said. Dr Bob Anderson revealed that he and The discovery attracted significant his colleagues had identified the three media attention. In this photo, Dr key proteins in gluten that were toxic for Anderson is talking to TV news crews people with coeliac disease. Dr Anderson about the finding, in a press conference said it had been 60 years since gluten was held at the institute.

Discovery tours

The institute’s discovery tour program information may be useful in developing Ivanhoe Grammar School, McKinnon has received a phenomenal public blood products with a longer shelf-life, Secondary College, Redcliffs Secondary response this year. new research into ‘pro-survival’ proteins College Mildura, Nanyang Polytechnic Almost 700 people from 30 groups that are important in the development of University, Singapore, Rotary Club of attended our discovery tours where they blood cancers, and boosting the immune Eltham, Royal Women’s Hospital senior found out about the research underway at system as a means of treating chronic management group, and University High the institute. Our researchers volunteer virus infections. School teachers. their time to take attendees on a tour Privately organised tours throughout Brigitte, a student from McKinnon of their laboratories and share their the year included visits from school Secondary College, said she’d had a latest research findings and insights into groups, Probus groups, golf clubs, private great experience at the institute. “It’s disease and human health. organisations, other research institutes, so interesting, I think it’s such a great During the year, scientists presented hospitals and universities. Some of the experience just to see the amazing job their research findings on breast stem groups that attended tours this year [the researchers] are trying to do to,” she cells and their role in breast cancer, included the Australian Cancer Research said. “All the research into immunology the lifecycle of platelets and how this Foundation, Berwick Ladies Probus, and disease, it’s just mind-blowing.”

56 Walter and Eliza Hall Institute Annual Report 2010-2011 Engagement

Engagement with schools

The institute is a strong advocate for science education and engages with school students to promote a vibrant science curriculum that will inspire the next generation of potential scientists. Public speaking commitments by institute staff and students in schools and in the community increased by 22 per cent in 2010-11.

Many of our staff and students to school students about careers for term partnerships between teachers and volunteer their time to participate women in science. This year some of scientists to provide inspiration and in engagement activities in schools. the schools our scientists visited were ideas for science learning in schools. Our students volunteer at the Gene Brunswick Early Learning Centre, They are also recruited to participate Technology Access Centre, where Carey Baptist Grammar School, in organised programs such as ‘Speed they develop and run experiments for Castlemaine North Primary School, Science’, the National Youth Science secondary school students. Researchers Malvern Primary School, Northcote Forum and I’m a Scientist, Get me out also visit schools to speak about their High School, Preston Girls Secondary of here! research. Our scientists are active in College and Scotch College. advocating for gender equity in health A number of our scientists are and medical research. They have visited involved in the CSIRO’s Scientists in a number of schools this year to talk Schools program, which fosters long-

GTAC: the Gene Technology Access Centre

GTAC is a collaboration between the chemistry in biological research, and the Walter and Eliza Hall Institute, the participation of the Victorian Minister Department of Microbiology and for Education, Mr Martin Dixon, in the Immunology at The University of ‘Genetech’ laboratory program during Melbourne and University High School. Education Week. The past year has seen more than Mr Brian Stevenson, outgoing director 6000 school students accessing GTAC’s of GTAC, said the centre provided an programs, including off-site visits to exemplar model for the establishment of primary schools. In 2011 GTAC hosted other specialist science centres. “It has two immunology-themed programs been a privilege to allow so many students combining laboratory activities with and teachers from all educational sectors seminars from scientists including Sir across Victoria to access some of the Gustav Nossal and Nobel Laureate country’s brightest young scientists and Professor Peter Doherty. Other eminent researchers through programs highlights have been the annual that reflect the contemporary nature of A junior participant in DNA Fun Sunday held teacher symposium on the role of bioscience,” he said. at GTAC during National Science Week.

I’m a Scientist, Get me out of Here!

In June 2011 Dr Krystal Evans from students voted for their favourite is perceived and understood by school the Infection and Immunity division participant in each of three ‘zones’ based students and what scientific issues competed in the Australian pilot of I’m on the scientists’ interest areas of health, concern them about the future,” she said. a Scientist, Get me out of here!, a federal food or general science. It is anticipated that I’m a Scientist, government-funded science enrichment Dr Evans was one of five scientists who Get me out of here! will be an annual and engagement program. competed in the Health Zone, answering program. I’m a Scientist, Get me out of here! questions on topics such as ‘are viruses involved 15 young Australian scientists alive?’, ‘what’s your biggest career goal?’ who spent up to two weeks online fielding and ‘how important do you think your questions from 1500 students at 34 research is?’ Australian schools, and participating in Dr Evans said the event sharpened online discussions with science classes. her communication skills. “It was great In the second week of the competition to get some insight into how research

Annual Report 2010-2011 Walter and Eliza Hall Institute 57 Donor and bequestor engagement

The support of donors and bequestors means a great deal to our scientists and directly advances the institute’s research program. This year marked the establishment of a new program to acknowledge and thank our donors and bequestors for their loyal support of the institute. In 2011, institute director Professor and on developments in the medical We were pleased to hear that guests Doug Hilton initiated a series of research research sector. enjoyed the research briefings, in briefings for long-standing donors, some During these presentations, Professor particular learning more about what of whom had supported the institute for Hilton acknowledged the significant the institute is doing and meeting other more than 35 years and were visiting the contribution of donors and bequestors to donors and bequestors. This feedback has institute for the first time. the establishment and development of the seen the institute commit to continuing Professor Hilton also invited individuals Walter and Eliza Hall Institute over the this program in 2012. who had notified the institute that they past 96 years, and the importance of this had made a gift in their will to join him support for the institute’s research. for updates on recent research initiatives

In May, bequestors joined deputy director Professor David Vaux (centre) for a laboratory tour followed by lunch hosted by director Professor Doug Hilton, who gave an update on institute research initiatives and on developments in the medical research sector.

Supporting research into childhood diseases

In December 2009, the late Mrs Paddy general manager Ms Maureen O’Keefe life and health outcomes for her fellow Pearl auctioned her home, Campania and head of fundraising Ms Deb Cutts. Australians and people around the world House, in Tasmania. Mrs Pearl kindly The group met with 70 residents of Saint is an inspiration,” he said. donated some of the proceeds to the Canice and Dr Oakes gave a presentation “Our scientists are working to find institute, which were used to establish on the latest developments in the institute’s causes, methods of prevention and a PhD scholarship to support research breast cancer research program. treatments for several diseases that have into diseases that affect children. Professor Hilton said he treasured the a huge impact on children, including To show appreciation for Mrs Pearl’s opportunity to meet with Mrs Pearl and leukaemia, rheumatic fever, malaria and support, institute director Professor Doug thank her personally for making it possible type 1 diabetes.” Hilton visited her at Saint Canice Lifestyle to establish the Cyril and Paddy Pearl The Cyril and Paddy Pearl Scholarship Village in Sandy Bay, Tasmania, to PhD Scholarship. was awarded to PhD student Mr Alan thank her for her generous donation and “Paddy Pearl’s philanthropy and Yap from the institute’s Infection and formally announce the $100,000 Cyril and belief in what we are trying to achieve Immunity division. Mr Yap is studying Paddy Pearl Scholarship. as an institute has given our researchers malaria, primarily a disease of children Professor Hilton was accompanied by tremendous encouragement. Her personal under five years of age and one of the breast cancer researcher Dr Sam Oakes, commitment to improving the quality of biggest paediatric killers worldwide.

58 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

The exterior of the renovated Walter and Eliza Hall Institute building in Parkville, Melbourne.

Annual Report 2010-2011 Walter and Eliza Hall Institute 59 The Board The directors of the Walter and Eliza Hall Institute of Medical Research board

Mr Leon A Davis AO Dip Prim Metallurgy SAIT Hon DSc Curtin Hon DSc Qld Hon DUniv UniSA FRACI FAIMM President Appointed: February 2001 Term expires: May 2013 Mr Davis became chief executive of Rio in 1991 as mining director, his Tinto Ltd and Rio Tinto plc on 1 January appointments included chairman of 1997 and retired from the position in Argyle Diamond Mines, Dampier Salt, 2000. Previously he had been deputy chief Wimmera Industrial Minerals and executive and chief operating officer of Kalimantan Gold. RTZ-CRA. In December 2000 Mr Davis Mr Davis joined the CRA Group in became chairman of Westpac Banking 1956 as a metallurgical cadet. In 1989 Corporation, stepping down from the he was appointed a group executive position in 2007. of CRA Limited. Until joining RTZ

Mr Steven M Skala AO BA LLB (Hons) Qld BCL Oxon Vice-President Appointed: June 1999 Term Expires: June 2014 Mr Skala is vice chairman Australia & member of the International Council of New Zealand of Deutsche Bank AG and New York’s Museum of Modern Art. a former senior partner of Arnold Bloch Mr Skala is a member of the advisory Leibler lawyers. council of the Australian Innovation He is chairman of Wilson HTM Research Centre, the Global Foundation Investment Group Ltd and a director of and the Grievance Tribunal of Cricket the Australian Broadcasting Corporation Australia. He is the immediate and Hexima Limited. He is deputy past Chairman of Film Australia chairman of The General Sir John Limited and the Australian Centre Monash Foundation, a director of the for Contemporary Art. Centre for Independent Studies and a

Mr Roger E Male LLB Adelaide Dip Acctg Swinburne Honorary Treasurer Appointed: June 1998 Term Expires: May 2013 Mr Male was a partner of Coopers & Mr Male is also a member of the Almond Lybrand for more than 20 years and Orchards Limited compliance committee retired from the firm as a member of its and the Nillumbik Shire Council audit national committee and Melbourne office advisory committee. managing partner in 1998. He is a director of Goldman Sachs Management and Partners Ltd, and the Uniting Church Funds Management Ltd.

60 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

Professor James Angus AO BSc Syd PhD Syd FAA Appointed: November 2003 Term expires: at discretion of The University of Melbourne Professor Angus is dean of the and the Victorian Comprehensive Faculty of Medicine, Dentistry and Cancer Centre. He is past president Health Sciences at The University of of Medical Deans Australia and New Melbourne. He was president of the Zealand, and is honorary secretary university’s academic board and has to the Victorian Rhodes Scholarship served on the university’s council as Committee. Professor Angus was well as the council of the Australian awarded the Gottschalk Medal in Academy of Science. 1984, the Centenary Medal in 2003 He currently serves on the boards of and the Australian Citation Laureate Melbourne Health, the Mental Health Award for Pharmacology in 2004. He Research Institute, the Victorian was appointed Officer of the Order of Institute of Forensic Medicine, Australia in June 2010.

Mr Mike C Fitzpatrick BA (Hons) Oxon BEng (Hons) UWA Appointed: February 2001 Term Expires: February 2013 Mr Fitzpatrick is chairman of the Airstralia Development Group Pty Ltd Australian Football League, Treasury (Perth Airport). Group Limited, Infrastructure Capital Mr Fitzpatrick was a premiership Group, and a non-executive director of captain (1981, 1982) with the Carlton Rio Tinto plc. Football Club in the Australian Football He is the founder and former managing League and a first-grade cricketer. He director of Hastings Funds Management was formerly a member of the Melbourne Limited. In that role, Mr Fitzpatrick Park Tennis Centre Trust, a director of was a director of a number of Hastings- the Carlton Football Club, chairman of managed investments including Pacific the Australian Sports Commission and, Hydro Limited, Global Renewables in the early 1980s, vice-president of the Limited, Utilities of Australia, AFL Players’ Association. Australian Infrastructure Fund and

Professor Jim McCluskey BMedSc MB BS MD UWA FRACP FRCPA Appointed: April 2011 Term expires: at discretion of The University of Melbourne Professor Jim McCluskey became the for more than 20 years and is editor-in- deputy vice-chancellor (research) at chief of the international immunogenetics The University of Melbourne in March journal Tissue Antigens. 2011. Prior to this he was the pro vice- He is a member of the board of chancellor (research partnerships), chair directors of the Florey Neurosciences of Microbiology and Immunology and Institute, Bionics Institute and a member deputy head of that department. of the Nossal Institute for Global Health. Professor McCluskey has an Professor McCluskey replaced international reputation for his research Professor Peter Rathjen as The University in basic and clinical immunology. He has of Melbourne’s representative on the consulted for the Australian Red Cross institute board in March 2011.

Annual Report 2010-2011 Walter and Eliza Hall Institute 61 Dr Graham F Mitchell AO RDA BVSc Syd FACVSc PhD Melb FTSE FAA Appointed: July 2007 Term Expires: June 2013 Dr Mitchell has detailed knowledge of of research in the R&D division of CSL the academia-industry interface and Limited. Dr Mitchell is an adviser on completed his PhD at the Walter and innovation to the Victorian, Tasmanian, Eliza Hall Institute in the late 1960s. In Northern Territory and Federal 1973, after postdoctoral experience in Governments and jointly acts as chief the US, UK and Switzerland, Dr Mitchell scientist for the Victorian Government returned to the institute and established departments of Primary Industries and a program on the immunology of Sustainability and Environment. He is parasitism. a non-executive director of Antisense In 1990, Dr Mitchell was appointed Therapeutics Limited, Compumedics director of the Royal Melbourne Limited, AgVic Services Pty Ltd, Adelaide Zoological Gardens but returned to Research and Innovation Pty Ltd and biomedical research in 1993 as director Avipep Pty Ltd.

Mrs Linda B Nicholls AO BA(Econ) Cornell MBA Harvard Hon FAICD Appointed: February 2001 Term Expires: February 2013 Mrs Nicholls is a corporate adviser is also vice-president and a member of and a director of a number of leading the Harvard Business School Alumni Australian companies and organisations. board. She runs her own corporate She is chairman of KDR (Yarra Trams), advisory practice specialising in business and a director of Sigma Pharmaceutical strategy in financial services and health Group, Fairfax Media, and the Australian care. Mrs Nicholls has more than 30 Institute of Company Directors. years experience as a senior executive Previously she was chairman of and company director in Australia, New Healthscope and Australia Post, and a Zealand and the United States. director of St George Bank. Mrs Nicholls

Ms Kate J Redwood BA BSW (Hons) Monash Appointed: August 2009 Term Expires: August 2012 Ms Redwood has held a number of senior Advisory Committee and for many management positions including CEO of years was president of the Carlton Senior the Australian Physiotherapy Association, Citizens’ Centre. executive director of Australian Red Ms Redwood is a member of the Cross Victoria, and executive director of Melbourne Health board and chairs the the Victorian Council of Social Service. Melbourne Health community advisory A former councillor for the City of committee. In 2010, she became a director Melbourne, Ms Redwood has chaired of Hepburn Wind. Ms Redwood was a number of standing committees as awarded the Centenary Medal in 2001 well as the Yarra/Melbourne Regional for services to local government and Library Board, the Melbourne Disability the community.

62 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

Mr Christopher W Thomas BCom (Hons) MBA Melb FAICD Appointed: February 2001 Term Expires: February 2013 Mr Thomas joined executive search Australian Institute of Management. He firm Egon Zehnder International in has served on the board of the Corps 1979 and was managing partner of the of Commissionaires (Victoria) and the Melbourne office from 1986 to 2003. He council of the Australian Film, Television was also leader of the firm’s global Board and Radio School. He was a board Consulting Practice Group (1998–2006) member of the Heide Museum of Modern and chaired the firm’s twice-yearly Art for nine years (and its chairman for international partners’ meetings from three years), chairman of the Victorian 1997 to 2007. Community Foundation and president of Mr Thomas is a fellow of the Australian the Melbourne Business School Alumni. Institute of Company Directors and the

Ms Catherine M Walter AM LLB (Hons) LLM MBA Melb FAICD Appointed: February 2001 Term Expires: February 2013 Ms Walter is a non-executive director In 2003, Ms Walter was appointed a of Australian Foundation Investment Member of the Order of Australia for Company, the Reserve Bank’s Payment her service to business, particularly Systems Board, Victorian Funds as a director of a number of public Management and Victorian Opera and companies, to the arts, to the law, and chairman of the Australian Synchrotron. to the community through the City of She practised law for 20 years as a Melbourne. She was awarded a Centenary commercial lawyer, which included a Medal in the same year. term as managing partner of Clayton Utz in Melbourne. Ms Walter is a former commissioner of the City of Melbourne.

Professor Ingrid Winship MB ChB MD Cape Town FRACP FACD Appointed: June 2007 Term Expires: June 2013 Professor Ingrid Winship is the inaugural Clinical Genetics and associate dean for chair of adult clinical genetics at The research in the Faculty of Medicine and University of Melbourne and executive Health Sciences. director of research for Melbourne Professor Winship is a member Health. of the Victorian Cancer Action Plan A medical graduate of the University of implementation committee, NHMRC Cape Town, she completed postgraduate Human Genetic Advisory Committee, training in genetics and dermatology. Victorian Life Sciences Computation In 1994, Professor Winship took up an Initiative steering committee and academic position at the University of the Australian Synchrotron clinical Auckland and later became Professor of advisory panel.

Annual Report 2010-2011 Walter and Eliza Hall Institute 63 General manager’s report

Building redevelopment Grand Challenges Explorations grants, 60 cents from government for indirect administered by the Bill & Melinda Gates costs. This is in place of the current Over the past financial year a Foundation, successfully progressed to complex multi-tiered system which only significant milestone was reached with stage 2 funding; and we were awarded provides 28 cents in each research dollar the handover of the institute’s new west two Human Frontier Science Program for indirect costs. wing, which was completed in December collaborative grants. During the year the institute has reduced 2010. The project was achieved on time Three institute laboratory heads costs and improved efficiencies by: and on budget, producing a first-class attracted new fellowships, with two t
renegotiating contracts for insurance, building of which the institute and NHMRC senior research fellowships and cleaning, gas and electricity; its wider community are very proud. a senior medical research fellowship from t
entering into a collaborative agreement Refurbishment of the east wing is now the Sylvia and Charles Viertel Charitable with The University of Melbourne for underway and will continue into 2012, Foundation being awarded. access to library services; resulting in a fully-integrated $185 While fighting budget cuts, applying t
consolidating waste management under million research facility. The success of for grants and raising funds for research a broader shared operating agreement the project to date has been made possible throughout the year, the institute with Melbourne Health; by the strong partnerships that were has been furthering its continuous t
outsourcing courier services; developed early between the institute and improvement strategy of keeping costs t
redesigning service delivery models for the architects (Denton Corker Marshall low and improving operational efficiency information technology, bioservices, and S2F), the builders (Baulderstone’s to ensure that every dollar raised, whether imaging and media production; BPL) and the consultant team (Aurecon, from competitive peer-reviewed grants, or t
carrying out a store tender process; Donald Cant Watts Corke and others). philanthropic, corporate or government t
reviewing costing and charging models donations and grants, goes as far as for scientific services; Financial sustainability possible, thereby ensuring the institute’s t
making progress towards reducing Relationship building also underpins long-term financial sustainability. leave liabilities; the institute’s approach to raising funds This includes funds received from t
introducing online compliance for research. We are focused on getting the Victorian Government (under the training; Operational Infrastructure Scheme) to know our supporters and their needs, t
enhancing human resources and and the Australian Government (under whether they are individual donors, finance information systems; and the Independent Research Institutes trusts and foundations, corporations or t
implementing an electronic document Infrastructure Support Scheme) for the government. Over the past year many management system. of these supporters played a pivotal role indirect costs of research. Contributions in supporting the institute-initiated received through these schemes are Discoveries Need Dollars campaign. desperately needed by the institute to The general manager’s advisory group: back As a result of this national campaign fund the infrastructure and operations row (from left), Mr Steve Droste, Dr John and everyone’s combined efforts, the that support the research. The institute Wastell, Ms Deb Cutts, Ms Maureen O’Keefe, Mr Paul Fraser, Mr Murray Jeffs, Mr Stanley campaign was successful and government is advocating for a simple transparent system where every dollar received for Balbata; front row, Ms Penny Fannin, Dr Julie cuts to medical research funding did not Mercer, Dr Helene Martin, Dr Catheryn O’Brien, direct research costs is supplemented by eventuate. However, there was also no Mr Michael Rubira, Ms Josephine Marshall. significant increase in medical research funding, at a time when there are four applications for every one project grant awarded by the National Health and Medical Research Council (NHMRC). Despite the ongoing intense competition for research grants, institute scientists have continued to be successful in obtaining competitive grant funding. Our success rate for project grants awarded through the NHMRC was again amongst the highest in Australia, with slightly more than 50 per cent of our applications funded. In addition, two of our largest NHMRC program grants were renewed. On the international stage, we were awarded a National Institutes of Health (US) Creative and Novel Ideas in HIV Research grant; one of our

64 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

Research technology and services The institute’s newly-established Institute, the Peter MacCallum Cancer for proteomics and the operations Scientific Services Committee and Senior Centre and the Victorian Comprehensive and personnel relating to proteomic Technology Planning Group have already Cancer Centre, among others. experiments. A mixed collaborative played an important role in assessing During the year a major restructure research and service model has been our current and future scientific services of the proteomics facility, led by the developed and the facility will operate as and technology needs. We have formed new head of the Systems Biology and a reference site for advanced proteomics technology partnerships with equipment Personalised Medicine division, Professor instrumentation. This will give our suppliers by becoming a reference or pilot Liam O’Connor, was completed. This researchers and our external clients access site in the areas of imaging, proteomics involved ending our joint agreement to the latest mass spectrometric and and flow cytometry. Further, equipment with the Ludwig Institute for Cancer bioinformatic analysis techniques. sharing has been made possible through Research (LICR) and the Walter and Eliza academic collaborations with the Bio21 Hall Institute taking full responsibility

Planning, legal, compliance and risk The institute’s new planning peppercorn rent, and is awaiting signature audits were conducted during the year: documents, including the 2010-2015 by the Victorian health minister. fundraising, travel, salary expenditure, Strategic and Operational Plans and During the year the institute’s key scientific services cost recovery, budget have come to the end of their compliance committees: Human procurement and health and safety. first year and a report of progress against Research Ethics, Animal Ethics, Safety, key strategic performance indicators has and Biosafety, all met regularly. Reports been prepared for the board. Each year were provided to the board and/or senior the plans will be reviewed as part of the management as required. annual planning and budget cycle to The institute risk management strategy ensure they are current and relevant. and crisis management plans continue The institute and LICR team behind During the year lease negotiations to be reviewed. The risk plan for the the move of the proteomics facility to successfully resulted in new leases with institute’s building expansion project the institute (from left): Mr Michael favourable terms for the institute’s has been reviewed and revised as the Rubira, Mr Simon Michnowicz, Professor Liam O’Connor, Dr Thomas proteomics facility and Systems Biology project moves from the main works to the Nebl, Mr Giuseppe Infusini, Ms and Personalised Medicine division in remaining works construction phase. Maureen O’Keefe, Mr Grant Thomas, buildings adjacent to the institute. The As part of an ongoing program of Dr John Wastell, Dr Andrew Webb. lease for our new, expanded institute has rolling audits approved by the Audit The new signage on the eastern been agreed for 99 years less one day for and Risk Committee, the following wing of the institute.

Annual Report 2010-2011 Walter and Eliza Hall Institute 65 Building our future

Towards gender equity in medical research

For decades the medical research These included: The institute and the GEC also sector has observed that women, who t
installing a family-friendly lecture participated in and sponsored several make up more than 50 per cent of its viewing room at all conferences held forums on equal opportunity and women undergraduate and PhD students, at the Mantra Erskine Beach Resort in research, including: are seriously under-represented at at Lorne, Victoria, allowing parents t
WiSE (Women in Science and senior levels. to participate in the conference while Engineering) Summit, 11 April 2011, This has been attributed to the caring for their children; Canberra; difficulties faced by women in making the t
making institute-sponsored access t
Gender Equity Workshop, 17 June 2011, transition from postdoctoral scientist to to childcare and associated services Melbourne. laboratory head and, from there, to more available for staff; and senior roles. t
continuing the childcare subsidy, which Institute director Professor Doug Hilton To address these issues at the institute provides senior female researchers with welcomes attendees to the Gender a Gender Equity Committee (GEC) was up to $15,000 a year towards the cost Equity Workshop, held in June 2011. formed in February 2010 to plan, facilitate of care for pre-school-age children. and administer gender equity initiatives. Currently, six laboratory heads and The GEC is co-chaired by Associate senior postdoctoral researchers are Professor Lynn Corcoran and Professor receiving this subsidy. Terry Speed and its members represent a A staff survey was undertaken this year cross-section of the institute staff. to help us understand the issues faced by This year, the institute appointed researchers in their career development four new female laboratory heads, at the institute. Feedback highlighted increasing the percentage of senior a number of issues, particularly for female researchers to 24 per cent from postdoctoral level scientists as they face 21 per cent in 2009-10. The institute is a the transition to laboratory head, often signatory to the United Nation’s women’s during their childbearing years. Further, empowerment principles. more focused, surveys are planned for This year, the GEC undertook a 2011 and beyond to continue to explore number of initiatives to improve facilities these issues. available at, and through, the institute.

Financial Sustainability Committee

Sustainability is one of the five pillars venture capital, law, marketing and of the institute’s Strategic Plan. One advertising and banking and finance. of the goals of this pillar is for the The committee is supporting and institute to gain independence from enhancing institute activities aimed at government funding cycles. This is securing our financial future and is a crucial if we are to recruit the scientists, welcome addition to our structure. purchase the technologies and undertake the bold experiments that will allow the institute to thrive into the future. To help meet this objective a board sub- committee, the Financial Sustainability Committee, was established in March 2011. The committee is chaired by board member Mr Chris Thomas. Some of the Financial Sustainability Joining Mr Thomas on the committee Committee members, from left to right: Ms Deb Cutts, Mr Rowan Kennedy, Mr are people with complementary skills and Michael Daddo, Mr Chris Thomas (chair), experience in industry superannuation, Professor Doug Hilton, Ms Caroline Johnston, Ms Maureen O’Keefe.

66 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

Building redevelopment

Since 2009, the institute has been levels of laboratories and scientific undergoing a significant building support services as well as an insectary redevelopment to almost double the to enable malaria researchers to target the size and research capacity of the critical liver stage of the malaria life cycle, institute. The redevelopment has and advanced cell and tissue imaging and largely been made possible through flow cytometry centres. the generosity of the Australian and The building redevelopment moved Victorian governments and The into the next stage in early 2011, with the Atlantic Philanthropies. refurbishment of the existing building On 16 December 2010, the keys to now in full swing. the new west wing of the building were handed over and we started the task The new laboratories in the west wing of moving the equipment and people of the institute. The new wing has been of dozens of laboratories into the new designed such that there are separate building. The west wing houses seven areas for offices and laboratories.

Institute donor for 46 years, Mr Eddie Brownstein

As an undergraduate medical student practice at the Wimmera Base Hospital in “David suggested that my studies in in Johannesburg in the 1950s, Mr Horsham, Victoria. bioethics and background experience Eddie Brownstein was confronted “For the first seven years I was on call made me a good candidate,” he said. “I daily by the impact of apartheid on the 24 hours a day for surgical problems,” Mr was honoured that David recommended community. “The black community had Brownstein said. “These were the days before me as a committee member.” very poor living conditions, very poor seat belts and with lots of speeding cars.” When asked what drives his wish to salaries and vast amounts of crime,” In 1965, following the death of his donate, Mr Brownstein contemplated the he said. “You saw that people couldn’t father, a stockbroker, Mr Brownstein question for some time. “Compassion,” sustain life, they couldn’t sustain suddenly found he had the funds to be he said. “It’s not religion, not justice and their children.” able to do more. “I took leave from work rules, or even individuals that drive me, Mr Brownstein says that when women because I had to do some thinking, and but compassion.” came into the clinic with their children, you can’t think enough when you are covered in rashes, septic and dying, the working,” he said. Mr Eddie Brownstein, pictured doctors would ask what had happened. After seeking advice from lawyers, below right with deputy director “‘Daar is niks geld baas’ [there is no Mr Brownstein decided to establish a Professor David Vaux, has supported the institute for 46 years. money boss]. We heard that so often.” philanthropic trust to improve the lives of Mr Brownstein and his medical student people needing care. He then heard about colleagues decided to do something. “We a new director appointed at the Walter decided to donate funds to support a and Eliza Hall Institute, Gus Nossal, and new program initiated by the Anglican asked if he could have a meeting. church to feed black children in primary “It was Gus who put me in the right schools. That was the beginning for me; direction,” Mr Brownstein said. “He when I saw poverty and decided I must do discussed the institute’s research with me, something,” he said. he introduced me to talented researchers A graduate in medicine from and I decided then to donate to the Witwatersrand University, Johannesburg, institute’s cancer research.” Mr Brownstein trained in general surgery Mr Brownstein’s support of the institute in Scotland and England. In 1961, after now spans 46 years and includes recent the Sharpeville massacre in South Africa, significant support for building works and he and his wife, with their two young construction. He also served for 11 years sons, decided to migrate to Australia. For as a member of the institute’s Human the next 25 years, Mr Brownstein worked Research Ethics Committee after being as a general surgeon in public and private approached by Professor David Vaux.

Annual Report 2010-2011 Walter and Eliza Hall Institute 67 Institute organisation

Board Board Sub-Committees Audit and Risk Committee Commercialisation Committee Financial Sustainability Committee Future Strategies Committee Advisory Groups Director Appointment and Promotion Professor Doug Hilton Human Research Ethics Committee Review Committee Investment Committee International Scientific Deputy Director New Building Steering Committee Advisory Council Professor David Vaux Senior Scientific Advisory Committee WEHI/RMH Clinical Advisory Group

Research Divisions Clinical Translation General Manager Business Development Bioinformatics Professor Andrew Roberts Ms Maureen O’Keefe Dr Julian Clark Professor Terry Speed Cancer and Haematology Professor Warren Alexander Professor Nick Nicola

Cell Signalling and Cell Death Biosafety Committee Professor David Vaux Advanced Research Scientific Support Occupational Health and Chemical Biology Technologies Services Safety Committee Professor David Huang Bioservices Building and Engineering Animal Ethics Committee Immunology Dr Catheryn O’Brien Mr Steve Droste Professor Phil Hodgkin Flow Cytometry Communications Infection and Immunity Dr Frank Battye Ms Penny Fannin Professor Alan Cowman Partnerships: Gene Targeting Services Finance Inflammation Dr Warren Alexander Mr Murray Jeffs ¯ACRF Centre for Therapeutic Professor Ian Wicks Target Discovery High-Throughput Fundraising Ms Deb Cutts Molecular Genetics of Cancer Chemical Screening ¯Australian Genome Research Professor Jerry Adams Dr Ian Street Human Resources Facility Professor Andreas Strasser Mr Paul Fraser Imaging ¯ARC Centre of Excellence for Molecular Immunology Dr Kelly Rogers Internal Audit Kangaroo Genomics Dr Stephen Nutt Mr Stanley Balbata Information Technology ¯Bio21 Cluster Molecular Medicine Dr John Wastell Laboratory Services and Biogrid Australia Professor Doug Hilton Operations ¯ Monoclonal Antibody Services Mr Michael Rubira Cancer Therapeutics CRC Stem Cells and Cancer Ms Kaye Wycherley ¯ Professor Geoff Lindeman Library and Information (CTx CRC) Professor Jane Visvader Management ¯Cancer Trials Australia Ms Josephine Marshall Structural Biology ¯Gene Technology Access Centre Professor Peter Colman Redevelopment Building Project ¯The HEARing Cooperative Systems Biology and Ms Wendy Carter Research Centre Personalised Medicine Mr Steve Droste Professor Liam O’Connor ¯Medical Research Dr Helene Martin Commercialisation Fund Research Grants Dr Julie Mercer ¯The Royal Melbourne Hospital Safety Systems ¯Type 1 Diabetes TrialNet Mr Tony Hendy ¯The University of Melbourne ¯Victorian Breast Cancer Research Consortium ¯Victorian Cancer Biobank ¯Victorian Comprehensive Cancer Centre ¯Victorian Government

68 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

Members of the institute 30 June 2011

The University of Melbourne Mr John L Greig Mrs Paddy Pearl The Royal Melbourne Hospital Sir Andrew Grimwade cbe (dec. 8 September 2011) Dr Susan Alberti ao Mrs Anne Grindrod Professor Roger Pepperell Professor James A Angus ao Mrs Jean T Hadges Mr David Percival Mr Donald Argus ac Dr Emanuela Handman Professor Emeritus Jim Pittard am Sir James Balderstone ac Mr Harry M Hearn am Lady Primrose Potter ac Mrs Ann D Bates Dr Margaret C Holmes Mr John B Prescott ac Mr Robert Bates Dr Thomas H Hurley ao obe Professor Peter D Rathjen Mr Lance H J Bauer Mr Darvell Hutchinson am Ms Kate J Redwood Mr Marc Besen ao Ms Helen Kennan Mr John B Reid ao Dr Peter Brennan Mr Warwick G Kent ao Mr Michael Robinson ao Mrs Beverley A Brownstein (Trustee of the Walter and Eliza Hall Trust) Mrs Margaret S Ross am Mr Edward G Brownstein Professor Emeritus Priscilla S Mr Fergus D Ryan Kincaid-Smith ac obe Dr Margaret N Brumby am Professor Graeme Ryan ac Professor Frank Larkins am Professor Tony Burgess ac Professor C B Schedvin Professor Richard Larkins ao Professor Christopher J Burrell ao Ms Carol Schwartz am Mr Gary W Liddell Professor Robert Burton Mr Andrew Scott Professor Emeritus Athol W J Lykke Dr David Campbell Professor John F Scott ao Professor Emeritus Ian R Mackay am Mr Terrence A Campbell ao Mrs Lousje J Skala Mrs Avis L Macphee am Professor David E Caro ao obe Mr Steven Skala ao (dec. 15 August 2011) Ms Eve Mahlab ao Mr Jack Smorgon ao Mr Alan J Chatterton am Mrs Robyn G Male Ms Linda M Sorrell (Trustee of the Walter and Eliza Hall Trust) Mr Roger Male Miss Ann A Sprague Lady Susannah Clarke Professor Ray Martin ao Dr John Stocker ao Professor Gordon Clunie Professor Emeritus Thomas J Martin ao Mr John W Stratton The Rt Hon Sir Zelman Cowen Mr Erich A Mayer am Ms Helen Sykes Mr John F Cowper Dr Neville J McCarthy ao Mr Bruce B Teele (Trustee of the Walter and Eliza Hall Trust) Mrs Jean M McCaughey ao Mrs Cheryl F Thomas Mr John Dahlsen Professor Jim McCluskey Mr Christopher Thomas Mr Stephen Daley Professor John A McKenzie am Mr John Walker qc Mr Leon Davis ao Professor Frederick Mendelsohn ao Mr Stanley Wallis ac Mrs Annette Davis Professor Emeritus Jacques Miller ac Ms Catherine Walter am Professor David de Kretser ac Mr Robert C Minter Mr John M Walter Mrs Helen M Diamond (Trustee of the Walter and Eliza Hall Trust) Mr John C Warburton Mr Ronald F Diamond Professor Christina Mitchell Mr Robert Warren Ms Melda K Donnelly Dr Graham F Mitchell ao Ms Marion J Webster oam Professor Ashley R Dunn Dr Judith A Mitchell Mr Kevin J Weight Mr John W Dyson Mr Hugh Morgan ac Professor Richard Wettenhall Dr Peter P-H Eng Dr George Morstyn Dr Senga Whittingham Mr Robert Evans Dame Elisabeth Murdoch ac dbe Mr David A Williamson Mr Mike C Fitzpatrick Mr Anthony Murphy Professor Robert Williamson ao Professor Richard Fox am Ms Linda Nicholls ao Professor Ingrid Winship Professor Alan D Gilbert AO Lady Lyn Nossal (dec. 27 July 2010) Mr Peter Worcester Mr Tom O’Brien am Professor James Goding Mr Robert Wylie Mrs Marion Page Mr John B Gough ao obe Sir Arvi Parbo ac Associate Professor Nicholas M Gough

Annual Report 2010-2011 Walter and Eliza Hall Institute 69 Supporters and donors

The support the institute receives from government, private donors, trusts, foundations and industry is vital to achieving our strategic goals and making the discoveries necessary to advance the understanding, prevention and treatment of disease. We are grateful for the trust our supporters have awarded us and are committed to honouring that trust.

Government support Trusts and Foundations Ramaciotti Foundations, The William The institute is thankful for the Trusts and foundations provide crucial Angliss (Victoria) Charitable Fund, support of the Victorian and financial support to the institute in its The Jack Brockhoff Foundation, The Australian Governments. pursuit of new and bold research. William Buckland Foundation, The This year we received $31.6 million It is with this support that we are able CASS Foundation Limited, The Rebecca in grants and $8 million in fellowships to strengthen collaborative arrangements L Cooper Medical Research Foundation, through the National Health and and programs with other research centres, The Dyson Bequest, The Leukemia & Medical Research Council. A further address capital requirements, and produce Lymphoma Society of America, The $293,000 in grants and $1.58 million in internationally-competitive research. J.H.A. Munro Foundation Limited, The fellowships was received. Further support We thank the following trusts and Lady Tata Memorial Trust, The Sylvia and was received from the Australian Stem foundations that have supported our Charles Viertel Charitable Foundation, Cell Centre, the Australian Phenomics applications for funding over the past and Joe White Bequest. Facility, the Australian Department 12 months: Arthritis Foundation of of Innovation, Industry, Science and Australia, Harold and Cora Brennen Research, the Cancer Therapeutics Charitable Fund, Cancer Council Cooperative Research Centre (CTx Victoria, Cure Cancer Australia CRC) and the HEARing Cooperative Foundation, Diabetes Australia Research Research Centre. Trust, Thomas William Francis & Violet The Victorian Government provided Coles Trust, The Bill & Melinda Gates $6.8 million of support through the Foundation, Juvenile Diabetes Research Dr Matthew Call (below left) was Victorian Breast Cancer Research Foundation, Leukaemia Foundation of awarded a Victorian Endowment Consortium, Victorian Cancer Australia, Leukaemia Foundation of for Science, Knowledge and Agency, Victorian Endowment for Queensland, Harold Mitchell Foundation, Innovation (VESKI) fellowship to continue his work at the institute. Science, Knowledge and Innovation, Multiple Myeloma Research Foundation, Dr Kelly Rogers (below right) received Victorian Neurotrauma Initiative National Breast Cancer Foundation, funding from the Harold and Cora and the Operational Infrastructure National Heart Foundation of Australia, Brennen Charitable Fund for the Support scheme. Prostate Cancer Foundation of Australia, institute’s Imaging Facility.

70 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

The Isabel and John Gilbertson Charitable Trust

During their lives, Isabel and John Mr Peter Gilbertson said. “Our family Gilbertson tried wherever possible to has experienced first-hand the impact assist those in need, as well as support of illness. We understand that medical and encourage community projects research can lead to new treatments for that strive to relieve distress for those the prevention and treatment of diseases in difficult circumstances. Theirs was a and can improve the health of millions fine example to their family and friends. of people.” Before they died they established The Mr Gilbertson said each year the Isabel and John Gilbertson Charitable trustees of The Isabel and John Gilbertson Trust, with each of their children as Charitable Trust take considerable time trustees, to encourage their extended to evaluate what they see as the priority family to continue to care for and help needs and community projects that others wherever possible. should be supported. “In this way, the Established in 2001, The Isabel and trust ensures that the current and future John Gilbertson Charitable Trust’s generations of the Gilbertson family will commitment is to support the community be actively involved in supporting people through short-term emergency relief and and projects in the community,” he said. long-term projects. The Isabel and John Gilbertson Isabel and John Gilbertson in 2001, the “We also have a strong interest in Charitable Trust has supported the year they established The Isabel and medical research,” one of the trustees, institute’s research program since 2007. John Gilbertson Charitable Trust.

The institute acknowledges the support of the following organisations

Annual Report 2010-2011 Walter and Eliza Hall Institute 71 Mrs Margaret Johnson, supporting malaria research

In January 1963 Mrs Margaret Johnson, “I realised that people with malaria do then a 23-year-old high school teacher, not have the energy to sow their crops travelled to Vanuatu to work on a for the next season and that people die church project to build a dormitory for a of malaria. That shaped my thinking of high school. donating to malaria research to support “I was there for a month, and had taken developing countries. You can relieve chloroquine as prescribed by my GP, and poverty if people can feed themselves.” returned to teaching in Australia. But Mrs Johnson’s interest in the challenges three months later came the headaches facing developing countries spans nearly and fever,” Mrs Johnson said. 50 years and she has donated to the Initial blood tests found no evidence institute’s malaria research for more than of malaria. It was her parents’ doctor, a 25 years. returned soldier from World War II who “Although I experienced malaria first- had seen malaria during service, who hand, I have been well ever since,” she successfully diagnosed Margaret’s illness. said. “I have benefited from living in an Two to three years later, Mrs Johnson affluent society and I feel strongly about was reading a UNESCO magazine and supporting malaria research to benefit learned how widespread malaria was in people in developing countries.” Mrs Margaret Johnson supports malaria developing countries and how it affects research for the benefits it can bring people’s lives. to people in developing countries.

Robert Evans, supporting governance and research

The institute is fortunate to enjoy the discoveries that they were making,” the support of community members he said. “Becoming a committee member who volunteer their knowledge, to do what I could to ensure this research experience and time to advance research continued wasn’t a difficult decision and discovery, volunteers such as to make.” Mr Robert Evans. It was while Mr Evans was on the For more than 20 years, Mr Evans was committee that he decided to donate to a member of the institute’s investment the institute’s research initiatives. committee, which protects and grows the “In the finance area, clearly you institute’s endowment to sustain research work with money. People in the finance and discovery into the future. Mr Evans, industry can earn a reasonably high who is now retired, worked in investment income. I felt humbled that the scientists’ and stock broking and volunteered his salaries were not as large as mine and expertise in financial management to they were doing a lot more for humanity.” the institute. Mr Evans retired from the investment Mr Evans said he returned to Australia committee in 2007. He said he would have in 1987, after a number of years working liked to stay on but, as he was taking a overseas, looking to help not-for-profit step back from the finance industry, he organisations that made tangible thought the time was right to let others contributions to improve people’s lives. It closer to the industry take the lead. was Mr Bruce Teele, then treasurer of the “I became a donor because I could institute and chairman of the investment see and hear about the scientists doing Mr Robert Evans, pictured right, and committee, who invited Mr Evans to join staggering things for medical research. It his wife Meredith with company the committee. made a big impact on me, and I continue secretary Mr Murray Jeffs. Mr “Bruce talked with me about the to be a donor today,” he said. Evans has contributed to the institute for more than 20 years. institute’s research and its scientists and

72 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

Donations $1000 and over

Estate of Eleanor Margrethe Albiston Ms Cecily Gilson RobMeree Foundation (The Stang Bequest) Estate of Keith Goldsbury Mrs Margaret S Ross am Anonymous - NSW Estate of Winifred Florence Grassick Rotary Club of Eltham Anonymous - Tas Mrs Jean T Hadges Mrs Pam Sargood Anonymous - Vic Mr Robert Hain Estate of the late Mary Annie Shearer Anonymous - Vic Estate of Maxwell Gardiner Helpman Jean Skea Memorial Trust Anonymous - Vic Estate of Sheila Mary Helpman Nell & Hermon Slade Trust Anonymous - Vic Mrs Jane Hemstritch Ms Pauline Speedy Anonymous - Vic Mr Graham B Jackson State Trustees Limited Hazel & Pip Appel Fund Ms Caroline Johnston Ms Jenny Tatchell Estate of Lindsay James Baldy Mrs Chlorine Kluck Mr Kim Teoh Ms Shirley Bartlett Estate of Laura Sampson Lamb The William Angliss (Victoria) Ms Katherine I Behrend Estate of Margaret Liggins Charitable Fund Bell Charitable Fund Mr John B Little The Jack Brockhoff Foundation Ltd Berwick Opportunity Shop Dr Darren Lockie The Decor Corporation Pty Ltd BHP Billiton Matched Giving Program Dr Neville J McCarthy ao The Dyson Bequest Mr Angelo Bladeni Mrs Christine McConnell The Isabel & John Gilbertson Charitable Trust Estate of C H Boden Irene & Ronald MacDonald Foundation The Goldschlager Family Charitable Estate of John Frederick Bransden Alan Gordon McMillen Arts Trust Foundation Harold and Cora Brennen Gift Fund The Walter and Eliza Hall Trust Charitable Fund Mrs Nina M Mace The J.H.A. Munro Foundation Ltd Estate of Thomas, Annie, and Albert H Maggs Charitable Trust Doris Burgess The Nossal Family Trust Mr Damien Miller Cardinia Beaconhills Golf Links The Lady Tata Memorial Trust Miriam Vale Golf Club Lady Members L R Cazaly Trust The Victoria Golf Club Ltd Bettye Victoria Mitchell Fund Estate of George Collie Mr Christopher Thomas Estate of Florence Helen Winiberg Moden Commercial Albury Ladies Golf Thomas Family Fund Dame Elisabeth Murdoch ac dbe Coolah Lady Golfers Mrs Olive Thurlby Mrs Anne E Naylor Craven Investment Pty Ltd Estate of Lila Joyce Underwood Ocean Shores Golf Club Estate of the late Jean Ellen Craven Vincentia Golf Club Lady Members Miss Lois E Oliver Mr Gordon Darling ac cmg Joe White Bequest Estate of Eva Orloff Mr Patrick Devlin Ms Marjorie E Wilks Pambula-Merimbula Golf Club Mr Ronald F Diamond Estate of Lorraine Florence Williams Mrs Paddy Pearl Estate of Mavis Rae King Dick Mr David A Williamson GT & L Potter Charitable Trust Drakensberg Trust Estate of Emily Vera Winder Agnes Maude Reilly Charitable Trust Estate of Ethel Mary Drummond Estate of Rosemary Anne Woodfull Estate of Margaret Lewis Reilly Dr Janice Dudley Yarra Yarra Golf Club Mr Dieter O Rinke Thomas William Francis & Violet Estate of Florence Mary Young Ms Judy Rix Coles Trust Mr Michael B Robinson ao Mr James R Gill

New donations of capital received in the 2010–11 financial year

Anonymous – Seminar Award Estate of the late Bettye Victoria Mitchell The full list of the institute’s permanent Tim Bates Memorial Diabetes Estate of the late RHW Moden named capital funds is on the Research Fund Sir Gustav Nossal Fund accompanying CD. Joy & Desmond Cory Cancer Barbara Parker Memorial Fund Research Fund Paddy Pearl Fund DA Craven Memorial Fund Lyndal & Jean Skea Leukaemia Fund Estates of the late JE Craven & late Estate of the late RM Tink MA Shearer Estate of the late MRK (Rae) Dick Estate of the late Nina May Mace

Annual Report 2010-2011 Walter and Eliza Hall Institute 73 The year at a glance

Income* Other income 6% Donation and bequest investment income 14%

Philanthropic grants, Australian fellowships, donations and Government bequests – Australian 58% 9%

Philanthropic grants and fellowships – overseas 4%

Victorian Government 9%

Expenditure Business development Administration 2% 6%

Building operation 7%

Support laboratories Scientific 22% laboratories 63%

The year in brief 2011 2010 Income for research ($000) (excluding investment income)* 70,748 64,233 Donation and bequest investment income ($000) 11,486 9,278 Expenditure on research ($000) 79,124 74,182 Net surplus (deficit) from research ($000) 3,110 (671) Number of staff and visiting scientists 585 558 Number of postgraduate students 135 103 Total staff and students (EFTs) 720 661 *Excluding income for institute redevelopment project of $136,000 (2010: $2,063,000)

74 Walter and Eliza Hall Institute Annual Report 2010-2011 Sustainability

Statistical summary for the year ended 30 June

2011 2010 2009 2008 2007 $,000s $,000s $,000s $,000s $,000s Research revenue Australian Government 45,973 39,291 37,409 33,446 29,230 Victorian Government 6,842 7,638 7,355 8,229 9,205 Foreign governments 557 953 543 443 776 Government revenue 53,372 47,882 45,307 42,118 39,211 Industrial grants and contracts 1,846 3,518 3,722 3,847 2,580 Philanthropic grants and fellowships - Australia 3,830 3,644 3,440 2,370 2,049 Philanthropic grants and fellowships - international 3,235 4,399 6,551 6,208 6,193 Investment income 1,2 11,486 9,278 10,007 8,561 7,543 Royalty income 2,513 1,071 1,356 1,943 3,198 General revenue 2,647 2,761 3,140 2,238 2,425 Donations and bequests 3,305 958 1,178 977 1,254 Non-government revenue 28,862 25,629 29,394 26,144 25,242 Total revenue for research 82,234 73,511 74,701 68,262 64,453

Research expenditure and financial results Staff costs 54,799 48,938 45,419 42,903 39,099 Laboratory operating costs 15,424 16,310 15,817 15,068 12,934 Laboratory equipment 2,862 2,474 2,591 2,271 2,192 Building operations 4,353 4,356 4,551 4,152 4,171 Administration 1,002 1,225 1,485 1,375 1,406 Business development 684 879 1,410 1,109 1,325 Total research expenditure 79,124 74,182 71,273 66,878 61,127 Results from research activities 3,110 (671) 3,428 1,384 3,326

Other income Profit on sale of long-term investments 3 7,712 1,151 1,372 5,260 9,072 Donations and bequests 1,566 2,120 9,879 34,738 1,524 Grants and donations for capital works 1 117 428 492 2,547 1,340 Total other income 9,395 3,699 11,743 42,545 11,936

Other expenses Loss on impairment write down of long-term investments (2,945) (203) (8,417) (9,336) – Depreciation and amortisation (6,375) (3,877) (3,025) (2,834) (3,270) Total other expenses (9,320) (4,080) (11,442) (12,170) (3,270) Net operating surplus 3,185 (1,052) 3,729 31,759 11,992 1. Excluding funds for WEHI redevelopment project 2. Income excludes share buy back dividends in 2011 ($4.75M) and 2007 ($7.93M) 3. Income includes share buy back dividends in 2011 ($4.75M) and 2007 ($7.93M)

Capital funds Permanent invested capital funds 134,457 129,802 126,475 115,072 75,561 General funds 138,752 90,534 35,998 25,814 31,404 Royalty fund 16,788 14,823 14,294 14,142 13,243 Leadership fund 16,182 15,873 15,672 15,226 13,881 Asset revaluation reserve 38,812 37,961 25,952 42,297 58,003 Total funds 344,991 288,993 218,391 212,551 192,092

Capital expenditure Property, plant and equipment 53,579 64,516 17,286 10,712 3,396

Staff numbers: (equivalent full-time) at 30 June 2011 2010 2009 2008 2007 Scientific research staff: – Senior faculty 64 52 52 50 54 – Other 147 143 156 130 112 – Visiting scientists 16 14 28 24 22 Supporting staff: – Laboratories and all services 358 349 323 315 326 Total staff and visiting scientists 585 558 559 519 514 Students 135 103 68 67 73

Papers published 250 249 246 224 241

Annual Report 2010-2011 Walter and Eliza Hall Institute 75 A story of two generations

Mrs Elizabeth Jenkins was in her early Mrs Holliday died in 2007, aged 82. of the institute, the way it is opening its teens when her mother, Mrs Pamela Now, her daughter Elizabeth finds her doors to the community and saying, ‘If Holliday, placed a copy of the Walter life mirroring some of her mother’s you’re interested, come in and have a look, and Eliza Hall Institute annual report interests. With a science degree from The which I did recently on a discovery tour’.” on the family table and said to her, University of Melbourne, Mrs Jenkins’ Mrs Jenkins attended an update meeting “Here, have a look”. career has included supervising teams in and lunch for bequestors, hosted by institute “That’s how it began,” said Mrs Jenkins. data centres for two global corporations. director Professor Doug Hilton. Her guest “Each year after that the Walter and Eliza “Then, three years ago, I thought about was her daughter, Emily, a medical student. Hall Institute annual report was left on what I wanted to do next,” she said. “I Emily has spent her gap year travelling to the table for me to peruse.” decided I wanted to be a primary school developing countries, including in Africa, A pre-school teacher, Mrs Holliday teacher, which I now am, and I love it.” and observed the impact of malaria in the started teaching in Melbourne at the end Like her mother, Mrs Jenkins became community, a disease that is one of the of World War II. Mrs Holliday taught a bequestor to the institute. “I think it’s institute’s research priorities. generations of children over the next 40 important to support organisations that Mrs Elizabeth Jenkins (left) and her mother, years, at times teaching two generations are doing amazing research to benefit our the late Mrs Pamela Holliday (right), have in the one family. health,” she said. “I like the transparency both left bequests to the institute. “Early in mum’s career, some of the children came from families that were really struggling and mum was involved in washing and providing clothes for these children,” Mrs Jenkins said. “At mum’s funeral, a lot of fellow teachers and supervisors said how inspirational she was, and how much she gave back to life.” A donor to the Walter and Eliza Hall Institute for more than 30 years, Mrs Holliday also made a gift in her will to the institute. “Mum made a bequest to support the institute’s medical research because she wanted to help people who were suffering,” Mrs Jenkins said. “She really believed in giving back to the community.“

A gift in your will to medical research Medical research is vital to improving healthcare and quality of life. Researchers at the Walter and Eliza Hall Institute of Medical Research have made several discoveries that have improved health outcomes for millions of people. A gift in your will to the Walter and Eliza Hall Institute is a lasting gift that will support our research efforts to improve human health with better prevention, detection and treatment of disease. For a confidential discussion, please contact Deborah Cutts, Head of Fundraising, email [email protected] or phone (03) 9345 2912.

Walter and Eliza Hall Institute of Medical Research 1G Royal Parade Parkville VIC 3052 Tel: (03) 9345 2555 Fax: (03) 9347 0852 www.wehi.edu.au

76 Walter and Eliza Hall Institute Annual Report 2010-2011 CD-ROM

The Walter and Eliza Hall Institute Annual Report 2010-11 CD-ROM contains a searchable PDF of the full annual report as well as the following: Discovery Engagement Staff photographs for each of the research divisions and the lists Staff service to the scientific and wider community of national and international exchanges undertaken by staff WEHI.TV animations Breast Stem Cells, Control of Breast Stem within those divisions Cells and Origin of Breast Cancer Full publications list Sustainability Education Full financial statements Full list of PhD and Honours projects in progress Membership lists of institute and board committees List of vacation scholars, UROP students and overseas Full staff list research trainees List of presentations that were given as part of our Wednesday seminar program and Postgraduate Lecture Series

Printed in Australia with soy based inks on 100% recycled fibre, FSC certified, carbon neutral paper.