Table of contents
Annual Review 2009 The John Curtin School of Medical Research
Introduction Staff & students 83 From the Director ...... 2 Emerging Pathogens ...... 84 and Vaccines Selected highlights...... 5 Genome Biology...... 85 JCSMR official opening...... 8 Immunology...... 86 JCSMR organisation ...... 9 Neuroscience...... 88 Committees ...... 10 Structural Biology...... 89 Research programs 11 Translational Medicine...... 90 Emerging Pathogens ...... 12 Australian Phenomics Facility. 90 and Vaccines High Blood Pressure ...... 90 Genome Biology...... 16 Research Unit Immunology...... 24 Students...... 91 Neuroscience...... 34 School Administration ...... 93 and Services Structural Biology...... 43 Translational Medicine...... 52 Publications, patents 95 Australian Phenomics...... 55 & presentations Facility Publications...... 96 Australian Cancer Research. . . 57 Patents...... 103 Foundation Biomolecular Resource Facility Presentations...... 104 Student presentations...... 109 Staff & student 59 achievements Contact with our community 111 Degrees...... 60 Commitment to serving . . . . . 115 Prizes and awards...... 61 our community
Visitors & 65 Support 123 research collaborations Grants...... 124 Visitors to JCSMR...... 66 Statistics...... 130 Research collaborations ...... 70 Donors...... 131
The John Curtin School of Medical Research Annual Review 2009 1 The John Curtin School of Medical Research
From the Director
“It is difficult to say what is impossible, for the dream of yesterday is the hope of today and the reality of tomorrow.” Robert H . Goddard, 1904
There has never been a time such as this for a “fair go” – it is eminently feasible to fulfill one’s potential today, at least in countries like Australia. For those with the motivation and determination, the possibilities are limitless. However, a major obstacle remains between each one of us and a bright future: illness.
My sister Fabiola and I in 1964, a few weeks before she died of cancer .
When cancer, lupus, blindness, depression, diabetes, SARS, AIDS, alcoholism, or a heart attack hit, lives are devastated, tremendous human and economic potential is wasted, and bright futures never materialise. How can we begin to address the immense personal, social, and fiscal burden of disease in Australia? Only by understanding the causes and mechanisms of illness can effective prevention and new cures be developed. The process of medical discovery is absolutely essential and it is at places like The John Curtin School of Medical Research that the frontiers of existing medical knowledge are pushed. We are exceptionally well poised to prosper in this exciting new decade.
When I started my medical research career at the United States National Institutes of Health in the late 1980’s, the approach of the day was to look at smaller and smaller areas with increasing depth and brute force technology in the hope of unraveling the most fundamental mechanisms that would pave the way for purposefully designed cures. That approach was the foundation for many disease-specific medical research institutes that are so abundant in the Australia of today. I shall never forget a Nobel Prize winner smirking as he replied to a question I asked in the early 1990’s about integrative work and proudly defended his “reductionistic” approach to medical research. Time sadly proved me right: reductionism failed us big time. New discoveries done in a reductionstic context have only marginally improved the plight of the seriously ill; moreover, the astronomical costs of healthcare go up faster than the country’s ability to cover them. It is currently thought that major breakthroughs require work that integrates various levels of knowledge and
2 The John Curtin School of Medical Research Annual Review 2009 is built across academic disciplines. Having in one, state-of the art, School several critical areas of medical research such as immunology, neuroscience, genomics, virology, structural biology, and translational medicine prospering side by side puts us in a very competitive position to develop cross-disciplinary work that can lead to groundbreaking new discoveries.
Discovery is the start of an exciting pathway towards health. But in this trajectory, as is often the case in our lives, the promise of a bright start is tempered by the realities of a perilous journey. Very few new drugs are currently reaching the market. In the last four years a major international drug company launched only one new drug, with modest success. We live in an era that has witnessed the paucity of effective translation from discovery into cures or new treatments. It is recognised that the cottage-industry process of translation, done in a fragmented manner by various areas of medicine is a qualified failure. From the ashes of the unfulfilled dreams of new cures, the discipline of translational medicine has recently emerged as a new area of academic medicine aimed at developing a systematic body of knowledge and a cadre of dedicated experts that can make the pathway from discovery to health more effective.
My strategic goals as Director of The John Curtin School of Medical Research are twofold: to advocate for and foster the process of medical discovery, while simultaneously nurturing the development of translational medicine as a bona fide medical specialty. In that regard, we have set up specialised programs in translational medicine as a new academic discipline. In the week of 16-20 August 2010 we had thirty-three lectures that covered the entire pathway from bench discovery to bedside, clinical trials, commercialisation, development of evidence-based healthcare guidelines, policy, and global health. Those began with the program around the award of the Curtin Medal to Professor Samuel Gershon (University of Pittsburgh, USA) on 16 August 2010. That was immediately followed by the highly successful Bootes Course on Translational Medicine: The Pathway from Discovery to Healthcare (17-20 August 2010), which was a precursor to our forthcoming Master’s Program in Translational Medicine, the first graduate degree program in translational medicine in the Asia-Pacific region (starting in the second semester of 2011). Additionally, on 30 August 2010 we hosted “Translation Research on the Brain: Accelerating the Pathway from Discovery to Healthcare,” as a First Annual National Conference at JCSMR. We were privileged to have presentations by academic leaders from across Australia; Baroness Susan Greenfield, University of Oxford, was the keynote speaker.
To further advance this field worldwide, we have conceptualised and organised at JCSMR the First International Conference on Translational Medicine that brings together on 1-4 November 2010 different types of domestic initiatives on translational science. We have in the program experts from the USA to present the American/CTSA perspective (Clay Johnston, UCSF; Carlos Pato, USC; Anantha Shekhar, Indiana), from the United Kingdom and Ireland to discuss the evolution of the Academic Health Science Centre (AHSC) concept in those countries (Dame Sally Davies, NHS; Alastair Buchan, Oxford; Stephen Smith,
The John Curtin School of Medical Research Annual Review 2009 3 Imperial College; William Powderly, Dublin), from China to highlight their rapidly evolving translational landscape (Jun Wang, BGI-China and Lin He, Chinese Academy of Sciences, Shanghai Jiao Tong University and Fudan University), from Singapore (Alain van Gool, Merck and Ranga Krishnan, Duke-NUS), from NIH (Alan Schechter and Anthony Hayward), from the USA Food and Drug Administration (FDA) (Leming Shi), and from Australia (Bruce Singh, University of Melbourne; Steve Wesselingh, Monash University; Bruce Robinson, University of Sydney; Colleen Nelson, Queensland University of Technology). Sir Gustav Nossal will present the John Curtin Lecture in Medical Research, “Translational Research as a Key to Global Health.” With this stellar group of speakers, who have never been brought together in one setting, we can contrast and compare different approaches to foster translational medicine across the globe. This JCSMR initiative will be of great benefit to Australia: it is critical to understand and learn what others across the world are doing in this area as we hopefully set the course for future large initiatives in translational medicine in this country.
I would like to end this introduction to our Annual Report by announcing the forthcoming launch of our new fund raising and awareness campaign: Project Australia for Medical Discovery and Translational Science. This new JCSMR initiative will dispel the misguided concept that we can invest minimally and just be opportunistic, capitalising on what comes up without substantial planning or expenditure. The entire scientific community disagrees with such a simple-minded perspective: a very organised, consistent, systematic and carefully planned effort is necessary to bring about medical discovery that is effectively translated into new cures. Based at ANU, we are well positioned to launch a national, Australia-wide project to foster discovery and to develop – as the new medical science discipline of translational medicine – the roadmap from scientific breakthrough to new cures and improved health in Australia and the world. Please continue to visit our website to stay updated on this and other JCSMR activities.
Professor Julio Licinio Director The John Curtin School of Medical Research (JCSMR)
Project Australia for Medical Discovery and Translational Science A fund raising and awareness campaign The John Curtin School of Medical Research The Australian National University Canberra, ACT 0200, Australia Launch 29 October 2010
4 The John Curtin School of Medical Research Annual Review 2009 Selected highlights 2009 JCSMR
Health through discovery . © The Royal Society Royal The © Dr Carola Vinuesa Professor Julio Licinio Professor Chris Goodnow
New Director announced for JCSMR
Professor Julio Licinio, a Psychiatrist, previously Miller Professor at the University of Miami Miller School of Medicine took up the position of Director of JCSMR in early September 2009. Announcing the appointment, Vice-Chancellor of The Australian National University (ANU), Professor Ian Chubb said “Professor Licinio has an outstanding track record in research in an area that is of national importance to Australia - the genetics at the interface of obesity and depression. He is in the top one percent of his field worldwide and has proven himself to be an energetic and innovative leader. I look forward seeing him continuing the work of previous directors of JCSMR.”
Professor Chubb also paid tribute to Professor Frances Shannon for stepping up to lead the School following the retirement of Professor Judith Whitworth. Professor Shannon continues to play a key leadership role in the School.
ANU immunology pioneer elected to The Royal Society
Professor Chris Goodnow was elected Fellow of the prestigious UK and Commonwealth Academy of Science, The Royal Society.
Gottschalk Medal
Dr Carola Vinuesa from JCSMR was awarded the 2009 Gottschalk Medal for research in the medical sciences by an early-career researcher. The Gottshalk Medal is presented by peak scientific body The Australian Academy of Science.
The John Curtin School of Medical Research Annual Review 2009 5 The Hon Kevin Rudd MP and ANU Vice-Chancellor Professor Ian Chubb Selected highlights 2009
PM opens the new John Curtin School of Medical Research Building
JCSMR Building was officially opened by The Hon Kevin Rudd MP Prime Minister of Australia on 27 May 2009.
ANU acknowledges the financial contributions made by the ACT Government and the Australian Commonwealth Government towards the construction of the new John Curtin School of Medical Research building.
Funding for Stage Three of JCSMR
ANU Vice-Chancellor Professor Ian Chubb welcomed the support provided to ANU in the Commonwealth Budget, which included $60M to complete Stage 3 of the JCSMR redevelopment project. Stage Three will house the ANU Eccles Institute of Neuroscience, an initiative that Professor Chubb said “would honour Sir John Eccles at the site where he did his Nobel prize-winning work”.
New DNA sequencers to speed up research
The time it takes to map a single human genome could be radically reduced thanks to two new next generation DNA sequencers that were unveiled at JCSMR in July.
Funding for the equipment was from an ARC-LIEF grant jointly submitted by ANU, The University of Canberra, CSIRO Plant Industry and CSIRO Entomology as well as financial contributions from each organisation. The sequencers will be housed at the Australian Cancer Research Foundation Biomolecular Resource Facility in JCSMR at ANU and be available for use by researchers from all institutions.
2008 Curtin Medal
One of Australia’s most distinguished cancer biologists, Professor Suzanne Cory, was awarded the Curtin Medal at a ceremony at JCSMR in August. The award recognises Professor Cory’s research on the molecular genetics of cancer and her lifelong contribution to research in the fields of molecular biology and biotechnology.
6 The John Curtin School of Medical Research Annual Review 2009 The goals of JCSMR are to
• conduct research of the highest international standard into fundamental life processes and the pathologies of these processes which cause human disease • play a leadership role in medical research in Australia • provide outstanding training in medical research for young scientists and health professionals • apply new knowledge for better health outcomes .
Selected highlights 2009
Memory lapses in our immune system revealed
In a breakthrough discovery, a research team at JCSMR, ANU, found a critical circuit in the immune system which, when faulty, causes loss of immunisation memory and would explain why some people suffer frequent and repeated infections.
“Vaccines that provoke long-lasting immunity are among the greatest advances delivered by health research, but the circuits that determine whether they work or not have been among the most difficult to decipher,” said Professor Goodnow co-leader of the research team.
This research was published in Nature Immunology in November 2009: Katrina L. Randall, Teresa Lambe, Andy L. Johnson , Bebhinn Treanor, Edyta Kucharska, Heather Domaschenz, Belinda Whittle, Lina E. Tze, Anselm Enders, Tanya L. Crockford, Tiphaine Bouriez-Jones, Duncan Alston, Jason G. Cyster, Michael J. Lenardo, Fabienne Mackay, Elissa K. Deenick, Stuart G. Tangye, Tyani D. Chan, Tahra Camidge, Robert Brink, Carola G. Vinuesa, Facundo D. Batista, Richard J. Cornall and Christopher C. Goodnow(2009) Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production. Nature Immunology 10: 1283 - 1291
Two high impact journals edited at ANU
The two highest impact journals in Australia are now edited at JCSMR. Molecular Psychiatry (MP) and The Pharmacogenomics Journal (TPJ) are both published by the Nature Publishing Group and edited by Professor Julio Licinio, Director, JCSMR, who founded MP in 1996 and TPJ in 2001, when he was at the National Institutes of Health and at UCLA, respectively. As the quantity and quality of science in Australia increases, it is critical that venues for the publication of high impact research be further fostered at the national level.
Finkel Prize for 2008
Dr Isaac Sakala was awarded the Alan and Elizabeth Finkel Prize for 2008.
The Alan and Elizabeth Finkel Prize is awarded every two years to recognise outstanding achievement in research carried out in JCSMR which has the potential to lead to improvements in health in developing countries.
Dr Isaac Sakala
The John Curtin School of Medical Research Annual Review 2009 7 JCSMR official opening 2009 The JCSMR Building was officially opened by The Hon Kevin Rudd MP Prime Minister of Australia on 27 May 2009 .
ANU acknowledges the financial contributions made by the ACT Government and the Australian Commonwealth Government towards the construction of the new JCSMR building .
The Hon Mr Kevin Rudd MP and ANU Vice-Chancellor Professor Ian Chubb unveil the commemoration stone .
Prime Minister Kevin Rudd with Emeritus Professor Frank Fenner at the opening .
8 The John Curtin School of Medical Research Annual Review 2009 JCSMR organisation 2009
ANU College of Medicine, Biology and Environment
The John Curtin School of Medical Research
Director, Professor Julio Licinio Deputy Director, Professor Simon Easteal
Research Programs & Program Leaders Emerging Genome Immunology Neuroscience Structural Translational Pathogens & Biology Program Program Biology MedicineScience Vaccines Program Program Program Program Dr Mario Professor David Professor Chris Professor Greg Professor Philip Professor Julio Dr Mario Professor David Professor Chris Professor Greg Professor Philip Professor Julio Lobigs Tremethick Goodnow Stuart Board Licinio Lobigs Tremethick Goodnow Stuart Board Licinio
Administration Administration Public Affairs & Director’s Office School Manager Education Director’s Office School ManagerCommunicationsPublic Affairs & Communications Ms Laura Vitler Mr Barry Webb Dr Madeleine Nicol Dr Anna Cowan Ms Laura Vitler Mr Barry Webb Dr Madeleine Nicol
Services and Support ACRF Microscopy & Technical Safety & Biomolecular Operations Cytometry Services Training Resource Facility ResourceResourse Facility Ms Stephanie Palmer MsMs CathiCathi MetcalfeMetcalf Ms Cathy Gillespie Mr Denis Coombes Ms Katja McKenzie
The John Curtin School of Medical Research Annual Review 2009 9 Committees 2009
From 2009, Faculty Board was Research Committee External Relations (until September) dissolved, and five new advisory Committee Professor P. Board Professor P. Board (Chair) (from September) Professor S. Easteal committees convened . Dr A. Cowan Professor C. Goodnow Mr H. French Dr M. Lobigs Group Leaders’ Forum (GLF) Dr B. Quah Professor T. Lamb (Chair) (until September) Professor M.F. Shannon (Chair) Dr M. Nicol continued to meet monthly to Professor G. Stuart Professor C. Parish Mr R. Sun discuss matters of importance Professor I. Ramshaw Professor D. Tremethick Dr C. Raymond to the running of JCSMR . Mr B. Webb Mr B. Webb Chair of Group Leaders’ Forum Operations Committee Professor A. Dulhunty Executive Committee • Professor I A. Ramshaw Ms C. Gillespie Professor S. Easteal (until December) Professor C. Hill Professor T. Lamb • Professor K I. . Matthaei Dr G. Huttley Professor I. Ramshaw (from December) Associate Professor G. Karupiah Professor M.F. Shannon (Chair) Ms K. McKenzie Ms C. Metcalfe Mr B. Webb Ms S. Palmer Dr C. Ranasinghe Education Committee Mr A. Reid Professor P. Board Mr B. Stewart Dr A. Cowan Ms M. Townsend Professor S. Easteal (Chair) Mr B. Webb (Chair) Ms H. French Mrs E. Weil Professor C. Goodnow JCSMR Safety Committee Dr M. Kole Dr G. Chaudhri (Chair) Dr M. Lobigs Ms S. Palmer Mr O. Luo Ms H. Domaschenz Professor G. Stuart Dr B. Quah Dr P. Milburn Dr R. Williams Dr J. Chen Dr M. Morris Dr M. Regner Ms D. Gooding Ms K. McKenzie
10 The John Curtin School of Medical Research Annual Review 2009 Research Programs
• Emerging Pathogens and Vaccines • Genome Biology • Immunology • Neuroscience • Structural Biology • Translational Medicine • Australian Phenomics Facility • Australian Cancer Research Foundation Biomolecular Resource Facility
The John Curtin School of Medical Research Annual Review 2009 Research program Emerging Pathogens & Vaccines
Program Head Dr Mario Lobigs
Group Leader
Cellular Microbiology Group Professor Tim Hirst
Molecular Virology Group Dr Mario Lobigs
Vaccine Immunology Group Professor Ian Ramshaw Molecular Mucosal Immunology Laboratory Dr Charani Ranasinghe Vaccine Immunology Laboratory Professor Ian Ramshaw
Viral Immunology Group Professor Arno Müllbacher
12 The John Curtin School of Medical Research Annual Review 2009 Molecular Virology Group http://jcsmr.anu.edu.au/org/epv/molvirology
Vaccinating against viruses which cause encephalitis
Dr Mario Lobigs Emerging Pathogens & Vaccines
Flaviviruses are an increasing Our research is focused on the molecular of traditional, non-adjuvanted, vaccine in burden on human health, and immunobiology of flaviviruses. This is a the absence of increased reactogenicity. are often transferred by the family of enveloped RNA viruses, which Equine immunisations with adjuvanted are mostly transmitted by the bite of a bite of a mosquito or tick . JE vaccine similarly showed enhanced mosquito or tick to the vertebrate host. vaccine immunogenicity, confirming that The flaviviruses include some of the most the adjuvant effect is not restricted to important emerging viral pathogens for rodent models. The vaccine trial also showed humans (dengue, Japanese encephalitis, cross-protective levels of immunity against yellow fever, West Nile viruses) and are an a related Australian flavivirus, Murray increasing burden on human health as a Valley encephalitis virus, against which result of climate change and population vaccines are not available. This is the first growth. There is an urgent need for new demonstration in small and large animal and improved prophylactic and therapeutic models of protection against multiple agents against members of this virus family. related flaviviruses using a single inactivated Our research addresses three aspects in vaccine, when formulated with the inulin- flavivirus biology and host/pathogen based adjuvant. The result has important interactions: implications in terms of vaccination against • the elucidation, at the molecular level, encephalitic flaviviral disease in Australia, of fundamental aspects of flavivirus given that the geographic expansion of replication, virulence and pathogenesis Japanese encephalitis virus in the Asia- • the characterisation of immune responses Pacific region, possibly associated with critical in recovery from infection in climate change, may give rise to a scenario mouse models of flaviviral disease where both viruses co-exist in northern regions of Australia. • the development of platform technologies for flaviviral vaccines. In other research in the area of structure- function analysis of flaviviral proteins we Last year we completed a Japanese encephalitis (JE) vaccine trial in collaboration describe a, so far, unique function of a with researchers in Adelaide, Brisbane and flaviviral signal peptide in balancing the Japan. This investigation examined the catalytic activity of two proteases, thereby immune-potentiating value of inulin, a facilitating virus morphogenesis and novel polysaccharide-based adjuvant, in demonstrate a duelling role of the glycans formulation with an inactivated JE vaccine. on the envelope protein of dengue virus, The adjuvanted vaccine elicited protective where an adverse effect on virus infectivity immunity in mice that was superior to is offset by enhanced release of virus that produced with 10-fold higher doses particles from the infected cell.
The John Curtin School of Medical Research Annual Review 2009 13 Vaccine Immunology Group
Emerging Pathogens & Vaccines
Molecular Mucosal Dr Charani Ranasinghe Immunology Laboratory Delivery of a novel vaccine against HIV http://jcsmr.anu.edu.au/org/epv/ Since all HIV-1 “systemic vaccine trials” the mucosal vaccination can induce better vacimmunology in humans have elicited poor outcomes, quality CD8+ T cells (T cells of higher avidity) Previous human trials of HIV there is now an increased awareness of compared to systemic vaccination. Therefore, AIDS vaccines have not been the potential importance of inducing in our laboratory we have performed studies local antiviral immune responses at successful, so we are looking to understand “how and why” the vaccine “mucosal surfaces”, particularly in the delivery route could influence the quality of at better ways of delivering genital and rectal tissues, the cervico- protective CTL immunity to HIV-1. During the vaccine to ensure a more vaginal tissues in females where the virus these studies we have made the remarkable positive outcome . is usually first encountered, and in the discovery that some Th2 cytokines (example gastro-intestinal tract, which appears to IL-13) play a crucial role in modulating be a major site of virus replication. It is CD8+ T cell avidity and protection against now widely accepted that purely systemic infection. Therefore, we are evaluating the immunisation strategies (for example: efficacy of a new-generation of recombinant intramuscular or intravenous), although inducing good systemic T cell responses, HIV-poxvirus vaccines that could enhance rarely induce optimal sustained mucosal T the magnitude and cytokine profile as well or B cell immunity. It has been shown that as the avidity of both mucosal and systemic a direct mucosal application of a vaccine HIV-specific CD8+ T cells and we are also is necessary to induce sustained mucosal studying the mucosal CD8+ T cell migration immunity. We have clearly shown that patterns following prime boost vaccination.
Vaccine Immunology Professor Ian Ramshaw Laboratory New approaches to HIV Immunity http://jcsmr.anu.edu.au/org/epv/ After two decades of intense research in approaches have reached clinical trial. vacimmunology HIV vaccine development there is still no Although these vaccine approaches are robust viable vaccine candidate. However, the effective in animal models these results development of an HIV vaccine must remain have not translated to the clinic. Further at the forefront of our research agenda with approaches that elicit even more effective the belief that the scientific obstacles can protective immune responses are required. be overcome. Our Group has made several Our Group is studying novel approaches to advances in the development of an AIDS elicit high levels of robust cell-mediated vaccine, including prime-boost immunisation immunity at the mucosae in the hope that and cytokine co-expression. Some of these this will protect against HIV infection.
14 The John Curtin School of Medical Research Annual Review 2009 Viral Immunology Group http://jcsmr.anu.edu.au/org/epv/viralimmun
Fighting viral disease
Professor Arno Müllbacher Emerging Pathogens & Vaccines
By studying host-virus The general aims of the group are A large number of virus models including flaviviruses, poxviruses, influenza and interaction we hope to 1. To generate new knowledge about parainfluenza viruses, alphaviruses and develop strategies to prevent the fundamental properties of the adenoviruses are employed in these studies. viral diseases such as immune system at the molecular, The availability and generation by our influenza . cellular and whole system level, with laboratories of gene-targeted mice defective particular emphasis on immune in immune effector molecules such as responses against viruses. perforin, the granzymes, and Fas receptor/ ligand allows us to elucidate important host/ 2. To study virus/host interactions at parasite relationships in the context of the the cellular and molecular level and host immune response. devise strategies for the prevention of viral disease. We are also exploring the interface between innate and adaptive immune responses, 3. Explore the use of gamma-ray particularly the role of type-I interferon inactivated virus preparations in sequential viral and bacterial infections. as inducers of cytotoxic T-cell Furthermore, we are employing our expertise memory, and their efficacy as vaccines in cytotoxic T-cell responses and in virus for control of influenza and inactivation to formulate a broadly virus Flavivirus encephalitis. strain-crossprotective anti-influenza vaccine.
Highlights of our research published in 2009 include:
• the discovery that the cytotoxic T cell enzyme granzyme B, when secreted by cytotoxic T cells, inhibits replication of the mousepox virus, ectromelia, in infected target cells in vitro • the successful testing of a gamma-ray inactivated universal influenza vaccine in mice. Mice vaccinated with a single dose of our candidate vaccine survived infections with diverse influenza strains, including infection with highly pathogenic avian influenza virus • the discovery that the cytotoxic T cell enzymes, granzymes A and B, which have been demonstrated to be required for optimal apoptosis induction of target cells in vitro, are not required for efficient and rapid target cell killing during in vivo antiviral cytotoxic T cell responses.
The John Curtin School of Medical Research Annual Review 2009 15 Research program Genome Biology
Program Head Professor David Tremethick
Group Leader
Cancer and Molecular Immunology Group Dr Mark Hulett
Chromatin and Transcriptional Regulation Group Professor David Tremethick
Computational Genomics Group Dr Gavin Huttley
Computational Proteomics and Therapy Design Group Professor Jill Gready
Epigenetics and Genome Stability Group Dr Danny Rangasamy
Gene Expression and Epigenomics Group Professor Frances Shannon
Molecular Systems Biology Group Dr Rohan Williams
Predictive Medicine Group Professor Simon Easteal
16 The John Curtin School of Medical Research Annual Review 2009 Chromatin & Transcriptional Regulation Group http://jcsmr.anu.edu.au/org/dmb/chromatin
The epigenetic code: The link between chromatin structure & function during development
Professor David Tremethick Genome Biology Program
Regulation of gene It is now clearly established that the central upon the composition of the underlying transcription relies on the regulator of eukaryotic gene transcription nucleosome. The key way the biochemical organisation of the genome is the organisation of the genome into composition of a nucleosome is altered chromatin. Chromatin performs this is by the substitution of one or more of into chromatin . crucial function by partitioning the the core histones with the corresponding genome into domains that are either histone variant. Our studies have focused open and transcriptionally active or closed on a major essential variant of H2A, H2A.Z, and repressed. Chromatin is built from and have demonstrated that one of its nucleosomes (histones plus DNA), the fundamental functions is to maintain the universal repeating protein-DNA complex stability of chromosomes. Specifically, to in all eukaryotic cells. Significantly, the maintain the integrity of the centromere tail of each histone protrudes on the and surrounding heterochromatin where outside of the nucleosome and is subject it is assembles, surprisingly, compacted domains using both active and inactive histone modifications. In an attempt to provide a dynamic link between chromatin structure and function, our in vitro structural studies have discovered a specific
Pachytene macromolecular determinant (an acidic spermatocytes, 4n patch) located on the surface nucleosome Round spermatids, 1n responsible for the ability of H2A.Z to Condensing spermatids, 1n promote the compaction of chromatin
Mature sperms, 1n and the formation of heterochromatin. Most interestingly, we have recently discovered a novel H2A histone variant in the mouse that lacks this acidic patch and Figure . The expression of a novel consistent with our model, incorporation to an extensive range of enzyme-catalysed H2A histone variant during mouse of this variant into nucleosomes inhibits modifications of site-specific amino acid spermatogenesis . In humans and mice, chromatin condensation, in contrast to residues in response to intrinsic and external spermatogenesis occurs in seminiferous H2A.Z. We have discovered that this new tubules (shown) . Mature spermatozoa signals. Functionally, it has been argued that histone variant is specifically expressed escape into the lumen (the centre of the combination of such modifications is a seminiferous tubule) . The DNA of during spermatogenesis (in the round recognised or read by specific chromatin mouse seminiferous tubules was stained spermatid stage, see Figure). We believe binding proteins involved in regulating with DAPI, and the chromatin was that uncovering the specific function of transcription and/or chromatin structure. immunostained with antibodies raised this novel histone variant will lead to new against our novel H2A variant . Clearly However, our recent work has shown that insights into the cause of male sterility. shown is the specific expression of the functional readout of specific histone this new histone variant in the round modifications is not sufficient to control spermatid stage . This interesting stage arises upon the completion of meiosis . chromatin function but is also dependent
The John Curtin School of Medical Research Annual Review 2009 17 Computational Genomics Group
http://jcsmr.anu.edu.au/org/genbio/compgen
Epigenetic processes & mutation
Dr Gavin Huttley Genome Biology Program
The ability of cells to switch Biological functions and processes the implications of this interplay between genes on and off are encoded by the specific ordering epigenetic state and human disease. of DNA nucleotides that make up an contributes significantly to Analyses of how the human genome individuals genome. In complex multi- human disease . differs from that of other species provides cellular organisms such as humans, every powerful insights into to the influence cell contains the same DNA sequence. of metabolic factors on mutation. The Producing cells that perform very different development of statistical methods and functions in individuals (e.g. immune cells algorithms for measurement of mutation and nerve cells) is achieved by regulating processes is a major objective of the the activity of genes. This capability is Computational Genomics Group. The provided by epigenetic processes such as results of this work are released as open DNA methylation and changes in DNA source software. Our software is in use by compaction. Alternating DNA between thousands of researchers across the world, methylated / unmethylated states or including numerous high profile studies such between compact / relaxed states is critical as the Human Microbiome project and the to switching genes on and off. Disruptions sequencing of the Opossum and to this capacity are known to contribute to Platypus genomes. disease in humans.
Evidence from this lab strongly links both these epigenetic processes with elevated rates of mutation. While a role between DNA methylation and mutation rates has been known for some time, the association between DNA compaction and mutation was less clear. We recently demonstrated that the rate of mutation varies along a DNA sequence in a periodic manner consistent with the known periodic placement of nucleosomes — the fundamental unit underpinning DNA compaction. This result unifies the two forms of epigenetic control as significant contributors to risk of mutation; the very act of encoding epigenetic information by DNA increases the risk that information will be destroyed by mutation. A major objective in the lab is to now understand
18 The John Curtin School of Medical Research Annual Review 2009 Computational Proteomics & Therapy Design Group http://jcsmr.anu.edu.au/org/genbio/cptd
A conceptual biology approach to understanding protein function in animals & plants
Professor Jill Gready Genome Biology Program
Our work will help crop and create novel links (“maps”) between data certain conditions to induce apoptosis and scientists develop plants with of different types. We then interrogate the cell death in Alzheimers’ disease. combined data matrix to find new insights greater productivity, and In the plant world, we have invented new into protein structure and function that we technology for the design of mutants features such as develop into predictions for further test by of the photosynthetic enzyme Rubisco drought tolerance . experiment and computation. Some of our with improved catalytic efficiency and recent findings illustrate the value and cost- substrate specificity; these have been effectiveness of this approach. validated experimentally in a model plant. Our research aims to understand how Using the conceptual biology and Rubisco is almost solely responsible for proteins carry out their functions in the comparative genomics approach, we are fixing carbon dioxide into the energy-rich cell and how they have been sculpted by systematically mapping the functional compounds of life. Our approach combined evolution to do so. Our findings provide evolution of the three prion protein (PrP) our computational insights on the enzyme’s the basic knowledge to understand family genes (PrP; Doppel, Dpl; and Shadoo, mechanism with phylogenetic analyses proteins’ normal functions in plants and Sho). For Sho – which we discovered by in developed from readily available structural animals, and their dysfunctions in disease. silico methods in 2003 – we have identified and sequence data. This allowed us to make The free availability of huge amounts of an RGG-box motif in the disordered precise predictions of multiple residues to biological information in international N-terminal region as having a potential RNA- mutate. In essence, we have invented a databanks – especially nucleotide and binding function; we have now validated procedure for reduction of sequence space, protein sequences and structures and this prediction both by experiment and that is to identify the subset of the protein’s gene expression data from all kingdoms computational simulations. We expect that residues that it is useful to mutate, what of life – provide new means for asking these protein-RNA interactions underlie they should be mutated to, and how multiple and answering our scientific questions. Sho’s now established functions in neuronal mutations should be grouped. With plant and The major approach we employ, development. We have also predicted and crop scientists, we are developing our method christened conceptual biology, aims experimentally validated a mechanism for for re-engineering more efficient Rubiscos to create hypotheses and initially test regulating co-ordinated transcription of into crop plants for greater productivity and them using existing data and literature the PrP and Dpl genes. This can explain specific features such as drought tolerance. information. In essence we re-purpose how the relative levels of the two proteins Other potential applications are biomass and data generated by other researchers, are controlled, and can be perturbed under biofuel production, and carbon sequestration.
Species Start End 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 Human 25 42 K GGRGG A RG SA RGG V RGG Mouse 25 41 K GGRGG A RG SA RG V RGG Dog 25 42 K GGRGG A RG SA RGG L RGG Bovine 25 42 K GGRGG A RG SA RGGRG AA Possum (Mdl) 25 42 K GGRGG A RG AA RGR S R SS Platypus 25 42 K GGRGG A RG AA RG AA RG A Chicken 25 42 K GGRGG S RG AA RG MA RG A Frog (Xl) 25 42 K GGRGG A RGG A RG SS RG T Frog (Xt) 25 42 K GGRGG A RGG A RG AS RG A Fish (Danio) 25 42 K GGRGG A RG SA RG TA RGG Fish (Fugu) 25 42 K GGRGG S RG SS RG SPS R S Fish (Tetraodon) 26 43 K GGRGG S RG SS RG SPS R S
The John Curtin School of Medical Research Annual Review 2009 19 Epigenetics & Genome Stability Group
http://jcsmr.anu.edu.au/org/genbio/epigenstab
Use of L1 retrotransposon as a novel breast cancer biomarker
Dr Danny Rangasamy Genome Biology Program
Our work may lead to new Breast cancer is the most common of breast cancer or in the prediction of strategies for future malignant disease in women. The worldwide cancer onset. Specifically, L1 biomarker is cancer treatments . incidence of breast cancer continues to useful in the prediction of genetic changes rise, and has become a leading cause of associated with the transition from normal cancer deaths. There is an urgent need to to hyperplasia to in situ breast carcinoma to discover new biomarkers for early detection invasive breast cancer. With collaboration as well as to identify new pathways or of ACT Pathology, Canberra Hospital, we are targets for drug therapy. More than 90 currently testing this L1 biomarker using a per cent of breast cancers are sporadic or panel of archived breast cancer tissues and acquired somatic mutations. It is believed confirming the association of L1 expression that genomic instability might promote with clinical and morphological features of the accumulation of genetic changes in breast cancer samples. apparently normal breast tissue, even before histological abnormalities are Given the deleterious nature of detectable. Although genomic instability is retrotransposon activity and genomic commonly found in invasive carcinomas, instability in breast cancer development, little is known about the timing of critical we are interested in the mechanisms by changes in early tumorigenesis or changes which the L1 retrotransposon is regulated associated with the transition from in normal healthy cells, but not in cancer normal cells to invasive breast carcinoma. cells. Using deep-sequencing technology We have recently identified mobile DNA combined with microarray analysis, we have elements ‘L1 retrotransposons’ that are recently identified a class of small non- differentially expressed in normal and coding endo-siRNAs as a key regulator of breast cancer tissue. In normal healthy L1 retrotransposons in the human genome. tissues, L1 proteins are completely absent Currently, we are testing the epigenetic role throughout the cell cycle. In contrast, L1 of endo-siRNAs including DNA methylation, Normal breast tissue . retrotransposon is overexpressed in several packaging retrotransposons into inactive clinically relevant breast cancer tissues. heterochromatin structures, and RNAi- The unchecked L1 activity would create mediated silencing pathways. This research havoc in the human genome, initially project will shed new light into how and through insertional mutations and later why disease states arise in breast tissues by genomic instability through high levels and how the altered expressions of L1 of double-strand DNA breaks, deletions, retrotransposons activate the process of and genomic rearrangements. Although breast cancer development. Unravelling the mechanistic pathways that activate L1 the relationship between small regulatory expression are not known, its expression endo-siRNAs and DNA methylation in Invasive breast cancer tissue . and its effect on genomic instability have the development of cancers may provide given rise to suggestion that it may serve new strategies for future therapeutic and as useful biomarkers in the early diagnosis diagnostic approaches.
20 The John Curtin School of Medical Research Annual Review 2009 Gene Expression & Epigenomics Group http://jcsmr.anu.edu.au/org/genbio/cytogene
Gene expression & the immune system
Professor M Frances Shannon Genome Biology Program
We examine the speed with The white blood cells of the immune different chemical modifications which which the immune system system need to be able to respond quickly influence how tightly they package the can turn genes on or off as but accurately when they encounter signs DNA . We have discovered that genes of infection . In response to activation a response to infection . that are quickly induced in response they immediately induce the expression of to activation have histones that are hundreds of genes . In the Gene Expression flagged differently to those that do not and Epigenomics Group we investigate respond . We have also investigated the the way in which immune cells control which genes are turned on and the speed changes that occur to the genes and at which these genes are induced . Many their packaging when activation occurs, of the induced genes code for proteins using high-throughput DNA sequencing known as cytokines that are secreted out technology . By sequencing the millions of the cell to send signals to other cells, of DNA fragments that are flagged in a while other genes code for proteins that particular way we can discover how every act within the cell to regulate further gene in the genome is marked . transcription and control the size or the proliferation of the cell . An important regulator of lymphocyte gene induction is the protein c- Rel . The activation and proliferation of lymphocytes is important to fight It controls the induction of many infections and cancerous cells but when cytokine genes, and the proliferation of it is excessive or uncontrolled the body’s lymphocytes . Recently we have own tissues can be damaged . discovered that it also controls the induction of a specific lymphocyte Genes are wound around histone proteins to keep them organised . To be turned on, subset called T regulatory cells, which are the start of the gene has to be opened up involved in controlling the activation of so that the transcriptional machinery can other lymphocytes and preventing access the DNA . Histones are flagged by auto-immune responses .
The John Curtin School of Medical Research Annual Review 2009 21 Molecular Systems Biology Group
http://jcsmr.anu.edu.au/org/genbio/systemsbio
Inter-individual variation in health & disease
Dr Rohan Williams Genome Biology Program
We use a highly multidisciplinary level at which to study the interplay approach to understanding the between genetic, epigenetic and environmental influences on individual differences between individuals, variability. The Human Genome Project and use these insights to seek has provided us with powerful new assays new approaches to improving that permit the genome-wide sampling of human health . molecular phenotypes, namely messenger RNA, protein or metabolite levels, and these have allowed a new level of insight into the Any two individuals will differ from one nature of genotype-phenotype relationships another in myriad ways, including in their that underlie complex trait architecture. appearances (morphology), behaviour Within this new experimental framework, and function (physiology), as well as we can examine the genetic, epigenetic susceptibility to pathogen infection, or environmental determinants on global response to a drug or the likelihood of gene expression in both model organisms developing a given disease. Understanding and humans. Our current and future work the biological basis for inter-individual is focused on two major problems: (1) how variation in these complex traits do genetic and epigenetic differences (phenotypes), and how to incorporate this between individuals result in demonstrable knowledge into effective personalised health differences at the level of gene expression? care, represents an outstanding challenge (2) how can we utilise these approaches to to contemporary biomedical research. While develop new “individualised” biomarkers for inter-individual variation is often equated diagnostic applications? A new problem we with genetic variation (differences in DNA are examining is how we can develop “post- sequence), substantial inter-individual genomic” biomarkers for use in the assessing variability, even in identical twins, can result preventative health interventions (dietary
● ● ●● ● ● ● ● ● ●●● ● ● ● ●● ● ●●●●● ● ● from exposure to different environmental and exercise modifications) in the context of ● ● ● ●●● ● ● ● ● ● ●●●●●●● ● ●● ●●● ● ● ● ● ● ● ●●● ● ● ● ● ● ●● ● ●●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● factors or differences in developmental metabolic syndrome. ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●●●● ● ●● ● ●●●● ● ● ● (epigenetic) processes. Accordingly, ●● ●●● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ●● Due to large and complex amounts of data ● ● ● ● ●● ● ● ● ●● ● understanding the interplay between ● ● ●● ● ● ●● ● ● ● ● ● ●● ● ●●● ● ● ● ● ● ● ●●● ● ●●●●● ● ● ● ● ● ●● ●●●● ●● ● ● ● ● ● ● ● ●●● ●●● ● ● generated by the new genetic technologies, ● ● ● ●● ● ●● ● ● ● ●● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● these factors that pattern phenotypic ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●●● ● ●●● ● ●●● ● ● ● ●● ●●● ●●●● ● ●●●● ● ●●● ● ●●●●●● ● ●●●●●● ● ●●●●●● ● ● ●●●● and the complexity of their application ●●●●●● ● ●●● ● ● ●●●● ● ●●●●● ● ● ●● ●●●●●●● ●●●● ● ●● ●●● ● ● ●●●●● ● ● ● ● ●● variation between individuals, and ● ● ●●●●● ● ●●●●●●●● ●● ● ● ● ● ●●●●●●● ● ●● ●● ● ● ● ● ● ●●●●●●● ● ● ● ●●● ●● ●● ●●● ●● ● ● ● ● ● ● ● ● to specific biological or health questions, ● ● ● ● ●● ●● ●● ● ● ● ● ● ● ● ● ●●● ●● ● ● ● ● ● ●● ● ●●●●● ● ● ●●●●●● translating these insights into new ● ● ● ●● ● ● ●●●●●●● ● ● ● ● ●●●● ● ●●●●● ● ● ●●●●● ● ● ● ●●●● ●●●●● ●● ●●● ● ● ● ●● ●● ●● ● ● ●● ● ● ●● ● ● ●● ● ●● ● ● ●● ● ● ● ● ● ●● ● ● ● tackling these problems requires skills and ● ●● ●●●● ●●● ● ● ● ● ● ●● ● ● ●●● ●●● ●●●●●●●●●● ● ●●●●● ●● ●●●●●●●●● ● ● ● ● ● ● ● ●● ●● ● ● approaches to improving human ● ● ● ● ● ● ● ● ● ●●●●●● ● ● ● ● ●● ● ●● ● ●●● ● ●●●●●●●● ● ● ● ● ● ●●● ● ● ● ●● ●● ●● ● ● ● ●●●● ● ● ● ●● ●●●● ●●● ●● ●● ● ● ● ● ● ●● ●●● knowledge that extends beyond the scope ●● ●●●● ● ●● ● ●● ●●● ● ● ● ● ●● ● ●● ● ●● ● ● ● ● ●●● ●●●●●● ● ● ● ● ●●● ● ● health, is the focus of our group. ● ●● ●●●●●●● ● ●●● ● ●●●●● ● ● ●●●●●●●●● ● ● ● ●●●● ● ●●●●●●●●●●● ●● ● ● ● ●●●●● ● ● ●●● ● ● ●●●●●●●●●●● ● ● ● ●●● ●● ● ●● ●● ●●● ● ●●●●●●● ● ● ● ●● ● ● ● ●●● ● ●●● ● ● ● ● ●● ●●● ● ● of any single scientific discipline. Hence, ● ● ●●● ● ● ● ● ● ● ● ●●● ● ● ●●●● ● ●●● ● ● ● ●●●● ●●● ● ● ● ● ● ●● ● ● ● ● ● ●●● ● ● ● ● ● ●●● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ●●● ● ●● ● ●●●● ●● ● ● ●● ● ● ● ●●●●● Most biological processes are ● ● ● ●●●●● by nature our work is inherently and ● ●●● ● ● ●●●●● ● ● ● ●● ●●● ● ●●● ● ●●●● ● ● ● ●●●●● ● ● ● ● ● ● ● ● ● ● ● ●●●● ● ●● ● ● ● ● ●● ● ultimately mediated by extensive highly interdisciplinary, drawing on ideas ● ● ●●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ●● ● ●● ● ●● ● ● ●● ●● ●●● ●● ●●●● ● ● ●● ● ●●●● ●● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● changes in gene expression, and and methods from the fields of molecular ● ●● ●● ● ● ● ● ● ● ● ● ●● ● ● ●●● ● ● ● ● ● ● ●● ● ● ●●●●● ● ● ● ●●●●●●●● ● ● ● ● ●● ● ● ● ● ● ● ●● ●● therefore this level of regulation biology, genetics, applied statistics, ● ● ●● ●●● ● ● ●● ● ● ● ● ● ●●●● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ●●●● ●● ● ● ● ● ● represents the logical phenomenological integrative biology and clinical research. ● ●● ● ● ● ● ●● ● ● ● ●
22 The John Curtin School of Medical Research Annual Review 2009 Predictive Medicine Group http://jcsmr.anu.edu.au/org/genbio/predictivemed
The evolution of human diversity & its impact on health & disease
Professor Simon Easteal Genome Biology Program
We are looking at ways in As humans, we have experienced substantial differences affect health and susceptibility which evolution has shaped evolutionary change over the past few to disease?’ Our overall aim is to develop hundred thousand years. Our social and better approaches to managing health the differences between cultural environments have played a and to intervening to prevent disease that human beings, including predominant role and psychological and incorporate knowledge of our peculiar mental and physical health neurological change has been particularly evolutionary past and the biological and important. One of the surprising features psychological differences between people of individuals . of this process is that it has led, not to an that it has produced. optimal ‘type’ of human, but to extensive By studying variation in DNA sequences physical, psychological and cognitive diversity. in human genomes we characterise how Some of this diversity has evolved by natural evolutionary forces, such as natural selection, but some of it is an unintended selection, have shaped human diversity. side effect of the evolutionary process. We are particularly interested in variation The extensive changes to our biology in repetitive sequences, which evolves very and psychology brought about by the rapidly and is know to have important complex evolutionary dynamic between effects on genome function, but which has our ancestors and their environments have been less well studied than other forms of resulted in vulnerabilities, trade-offs and human genome variation. imbalances, which now affect our health We use this information to design studies and make us susceptible to disease. of how the evolutionary history of genetic In our research we ask ‘Why are people so variation contributes to physiological and different from each other?’ ‘How have these psychological diversity and affects mental differences between people arisen during and physical health, across the entire human evolution?’ and ‘How do these lifespan. In this work we study, over many years, large cohorts of people of different ages, who are representative of the general population, collecting and analyzing information about their health, their lifestyles and their genomes.
Also, by studying patterns of gene expression we examine how the genomes of individuals respond differently to environmental and lifestyle changes and to interventions aimed at improving their health. We aim to use knowledge of these differences in genome function to develop a greater understanding of how biological processes in our bodies interact with our environment to maintain good health. This work forms a basis for a more preventative approach to managing health.
The John Curtin School of Medical Research Annual Review 2009 23 Research program Immunology
Program Head Professor Chris Goodnow
Group Leader
Asthma and Allergy Group Dr Dianne Webb
Cancer and Vascular Biology Group Professor Chris Parish Cellular Laboratory Professor Chris Parish Diabetes/Transplantation Immunobiology Laboratory Dr Charmaine Simeonovic Epigenomics Laboratory Dr Sudha Rao Matrix Biology Laboratory Dr Craig Freeman
Humoral and Auto Immunity Group Dr Carola Vineusa
Immunogenomics Group Professor Christopher Goodnow Cell Mediated Immunogenomics Laboratory Dr Ed Bertram Immune Tolerance and Signalling Laboratory Professor Christopher Goodnow Ramaciotti Immunization Genomics Laboratory Dr Anselm Enders
Infection and Immunity Group Associate Professor Guna Karupiah Infection and Immunity Laboratory Associate Professor Guna Karupiah Inflammation and Viral Immunopathology Laboratory Dr Geeta Chaudhri
Translational Research Unit Dr Matthew Cook (joint with Canberra Hospital)
24 The John Curtin School of Medical Research Annual Review 2009 Asthma & Allergy Group
http://jcsmr.anu.edu.au/org/imm/asthma
Asthma & the immune response
Dr Dianne Webb Immunology Program
Over two million Australians The prevalence of asthma is widespread that stimulate allergic inflammation and suffer from asthma . We and nationally affects over 2 million secondly, why 12-HETE is unable to block these signals in females. Because high are studying factors which Australians. Asthma is caused by a chronic allergic response to inhaled allergens levels of circulating oestrogen worsen the predispose to the disease, such as pollens, dust mite particles and incidence and severity of asthma in some and looking at a number of animal dander, and can be exacerbated women, this hormone may exacerbate questions including why by irritants such as cigarette smoke and allergic disease by inhibiting the 12-HETE- more women suffer from traffic pollutants. Persistent inflammation inducible protective pathway. These studies will provide a new avenue for therapeutic asthma, and why asthma in uncontrolled asthma ultimately triggers structural changes to the airways (Figure 1) intervention in asthmatics and will also runs in families . increase our understanding of why that cause chronic breathlessness and wheezing. Reasons underlying reproductively mature women are more susceptible to asthma. A. Normal B. Asthmatic the development of asthma are complex, but factors currently Why does asthma run in families? under investigation in the Asthma One factor that determines why some and Allergy Group are why the individuals develop asthma is an inherited incidence and severity of asthma predisposition to the disease. While many appears linked to enhanced potential asthma-related target genes have oestrogen production in women and been identified, studies of diverse population the genetic basis of why asthma groups have recently shown a link between commonly runs in families. Our Figure 1 . Diagrammatic representation of normal (A) and certain nucleotide changes in the gene research is focused on two main asthmatic airways (B) . The asthmatic airway lumen is encoding Glutathione transferase Pi (GSTP1) occluded with mucus and inflammatory cells, the airway themes: wall is thickened (remodelled) and the smooth muscle and the development of asthma. GSTP1 is band surrounding the airways constricts more easily . Why are women more an enzyme found in bronchial epithelial susceptible to asthma? cells and potentially plays an important Using a mouse model of asthma, role in detoxifying irritating, asthma- A. GSTP+/+ B. GSTP-/- we have recently identified a novel exacerbating chemicals such as those found pathway by which the lipid mediator, in air pollutants and cigarette smoke. Our 12-hydroxyeicosatetraenoic acid NHMRC funded studies have used Gstp- (12-HETE), attenuates the severity null mice to demonstrate GSTP1 plays an of asthma-like symptoms. However, important physiological role in suppressing a curious finding linked to these asthma-like symptoms (Figure 2). We are Zhou et al, 2008 studies was the observation that currently investigating the interaction Figure 2 . Lung sections comparing the allergic airways the ability of 12-HETE to alleviate between allergens and air pollutants and of mice that either express GSTP1 (A) or are deficient allergic disease is blocked in female how GSTP1 can reduce their potential in GSTP1 (B) . Mice deficient in GSTP1 have enhanced structural changes with increased collagen deposition mice. With the support of an to trigger allergic disease. This study will (blue) around the airways . The arrows indicate the Innovation Grant from the Asthma provide a fundamental understanding of airway lumen . Foundation we are investigating how our genetic makeup can dictate our firstly, how 12-HETE turns off signals susceptibility to allergic disease.
The John Curtin School of Medical Research Annual Review 2009 25 Cancer & Vascular Biology Group Cellular Laboratory
http://jcsmr.anu.edu.au/org/imm/canc-vascbiol
New approaches to controlling cancer & autoimmunity
Professor Chris Parish Immunology Program
We have developed drugs The Cancer and Vascular Biology Group insulin-producing cells is associated with which inhibit blood vessel is particularly interested in identifying both Type 1 and Type 2 diabetes. These growth in tumours, and novel approaches to controlling cancer studies have raised the interesting possibility and autoimmune diseases, such as Type I block an enzyme which that heparan sulfate replacement therapy diabetes. When primary cancers arise they could be used as a treatment for both Type 1 aids metastasis . We are also cannot grow beyond one to two millimetres and Type 2 diabetes. The Group has also studying the potential for in diameter unless they induce the growth shown that platelets play a crucial role in developing a cancer vaccine . of new blood vessels that supply them with cancer spread (metastasis) and represent oxygen and nutrients and remove toxic a target for the development of new anti- byproducts of metabolism. Similarly, blood metastatic drugs. vessels play an important role in the spread of cancer cells to other organs, the cancer In parallel studies the Group is investigating cells having to use a range of degradative a number of clever vaccination strategies enzymes to digest their way through blood that stimulate the immune system to vessel walls, particularly when they lodge in recognise cancer cells as foreign and distant organs. eliminate them. One of these cancer vaccines entered Phase I clinical trials in melanoma The Cancer and Vascular Biology Group patients in December 2009. Finally, basic has been able to develop relatively simple immunological research by the Cancer and sugar-based drugs that inhibit blood Vascular Biology Group has resulted in vessel growth in tumours and block a important advances. First, a blood borne key enzyme, called heparanase, that aids protein, called histidine-rich glycoprotein, cancer spread (metastasis). Such drugs are also being investigated as potential has been identified which may play an new anti- inflammatory agents and have important role in controlling autoimmune been shown to control the development of diseases, such as systemic lupus, by aiding Type 1 diabetes in mice. The diabetes studies the elimination of dead and dying cells. have also revealed that the complex sugar Second, the Group has discovered a novel molecule, heparan sulfate, is expressed at form of membrane exchange between extraordinarily high levels by the insulin- cells of the immune system which has producing cells in the pancreas and is, in the potential to dramatically enhance the fact, essential for the survival of these cells. immune response to both pathogens Indeed, loss of heparan sulfate from the and cancer.
26 The John Curtin School of Medical Research Annual Review 2009 Cancer & Vascular Biology Group Diabetes/Transplantation Immunobiology Laboratory http://jcsmr.anu.edu.au/org/imm/canc-vascbiol/tranimm
Pancreatic islet beta cells require highly sulfated heparan sulfate (HS) for their survival
Dr Charmaine Simeonovic Immunology Program
Transplantation of healthy The glycosaminoglycan heparan sulfate with FITC-heparin has shown that the islet cells may provide a (HS) is abundantly expressed in mouse and heparin is rapidly taken up by beta cells by pathway to the treatment human pancreatic islets in situ (Figure 1a). one hour but effects on beta cell viability HS chains consist of repeated disaccharides are only observed after 24 hours (Figure 3). of patients with established of glucosamine and uronic acid and are These findings suggest that HS is critical Type 1 Diabetes . heavily sulfated in regions along their for maintaining beta cell survival and length. In situ, they are covalently bound may affect gene expression. Hydrogen to the protein core of heparan sulfate peroxide treatment which induces the local proteoglycans (HSPGs). In production of reactive oxygen species, addition to localisation in the efficiently kills isolated beta cells but failed islet basement membrane BM to kill cells cultured with heparin, highly and extracellular matrix (ECM), sulfated HS or other HS-mimetics. These our immunohistochemical studies findings suggest that HS preserves the have demonstrated that HS is survival of islet beta cells at least in part by strongly expressed within islet beta protecting the beta cells from free radical- cells. Whereas the HSPG perlecan mediated damage. Such a mechanism would is localised in the islet BM, our compensate islet beta cells for their known studies have revealed HSPGs within the islet deficiency in free radical scavenger enzymes. cell mass (syndecan-1, glypican-2, agrin, Our previous studies in NOD/Lt mice CD44 and collagen Type XVIII) and within demonstrated that autoimmune destruction islet beta cells (syndecan-1, glypican-2, of islet beta cells in situ correlates with CD44 and collagen Type XVIII). Following degradation of islet HS by heparanase and isolation of islets in vitro, HS but not the the development of Type 1 diabetes (T1D). protein core of HSPGs is lost from the islet Furthermore, in vivo treatment with a tissue (Figure 1b). Beta cells subsequently heparanase inhibitor/HS-mimetic (PI-88) isolated from the islets consistently show protected NOD/Lt mice from developing T1D loss of viability (20–40% cell death). Culture by preserving islet HS. Our studies therefore of the beta cells results in further loss of suggest that preservation or replacement both beta cell HS and viability (65–75% of islet HS may represent an exciting cell death). We have demonstrated that therapy for rescuing beta cell survival and beta cell viability is dramatically rescued function in patients at the time of T1D by co-culturing the beta cells with highly onset and during islet isolation for clinical sulfated HS, heparin or certain HS-mimetics transplantation as a treatment for patients (5–10% cell death) (Figure 2). Co-culture with established T1D.
The John Curtin School of Medical Research Annual Review 2009 27 Cancer & Vascular Biology Group Epigenomics Laboratory
http://jcsmr.anu.edu.au/org/imm/canc-vascbiol/epi
Epigenomics & the immune system
Dr Sudha Rao Immunology Program
We are studying regulatory characterised key epigenetic marks carried correlation with cancer progression. We mechanisms which drive the by the H3.3 histone variant (Sutcliffe E. have also identified an additional layer Molecular and Cellular Biology 2009). We of regulation that further expands the expression of genes in cells of are now using this knowledge to decipher repertoire for epigenetic control of gene the immune system . the hallmarks of transcriptional memory expression. Our findings place the important in T cells at both the epigenetic and T cell signalling kinase PKC-θ and the invasive transcription factor level. Our ultimate enzyme heparanase in an emerging class of goal in collaboration with leading groups mammalian enzymes, which have functions in T memory cells (Doherty and Turner, beyond merely that of their traditional University of Melbourne; Kelleher and roles. Using state-of-the-art genome-wide There are many facets of transcriptional Seddiki, St Vincent’s Centre for approaches in collaboration with Agilent regulation that orchestrate the timed Applied Medical Research) is to identify the Technologies, we have identified an interplay and coordinated expression of genes molecular markings essential for between these novel chromatin-tethered essential for development and the rapid recall T cell memory responses, proteins and microRNA-mediated processes. phenotypic plasticity of eukaryotic which have important implications in organisms. The molecular mechanisms Collectively, all aspects of our work describe vaccine development. that underpin the expression of a paradigm by which distinct chromatin genes in lower eukaryotes have been The majority of epigenetic tags regulatory mechanisms could converge to extensively studied, but in comparison characterised to date have been located in drive gene expression programs within cells there is still much to be learnt about the N-terminal tails of histones. We are one of the immune system. In this exciting era the transcriptional mechanisms of the first groups to have characterised a of epigenetic research, we look forward to controlling mammalian genes. The novel phosphorylation mark in the globular unveiling how the mammalian genome can major thrust of my research team has domain of histone H3. Interestingly, we have be regulated by the complex interaction of been to unravel complex epigenetic- shown that this epigenetic tag is essential chromatin regulation, signal transduction signatures in transcription programs for active transcription of immune genes kinases and microRNAs in normal and (Figure 1) in the context of human T and remarkably appears to have a negative disease states. cell biology, as well as to understand dysregulatory mechanisms operating in cancer settings.
Non-allelic histone variants have emerged as key players in transcriptional control and chromatin modulation. My laboratory has generated a specific histone H3.3 antibody that has allowed endogenous profiling of this variant on inducible mammalian genes for the first time. We have identified a histone exchange mechanism on inducible genes during transcriptional activation and have
28 The John Curtin School of Medical Research Annual Review 2009 Humoral & Auto Immunity Group http://jcsmr.anu.edu.au/org/imm/humimm
Autoimmune diseases — the double edged sword of immunity
Dr Carola Vinuesa Immunology Program
The ability to “remember” Our group is trying to understand the We have shown that a mutation in the immunity to bacteria and links between memory antibody responses Roquin gene abolishes the necessary viruses is essential to the and autoimmunity. The ability to generate compartmentalisation of the co-stimulatory potent, long-lasting immunity is a key molecules CD28 and ICOS that normally proper functioning of our component of the mammalian immune controls T cell activation and germinal center immune system . Accidental system that protects us from the constant formation. It has also become clear that immunity to the bodies challenge of pathogenic bacteria and aberrant formation of Tfh cells contributes own cells can result in viruses. However, this ability is a double- to the development of autoantibodies and autoimmune disease such as edged sword, as perturbations can result in lupus. We have found that circulating Tfh cells can be found at very small numbers lupus, and Type 1 diabetes . autoimmune diseases. These diseases include lupus, type 1 diabetes, and rheumatoid in the blood of healthy individuals, but arthritis, and typically occur when the they are increased in a subset of lupus immune system cannot differentiate patients and their numbers correlate with between invading pathogens and the body’s disease severity. Other exciting discoveries own cells, resulting in the destruction of include the identification of BCL-6 as these cells. the key transcription factor that drives Tfh differentiation, exerting some of its Our research aims to unravel the complex influence through limiting microRNA- interaction of cells and molecules that mediated gene repression; and the results in the production of potent, demonstration of a direct role for IL-21 on B long-lasting immunity, and to identify cells that is important for the initiation and genetic abnormalities that interfere maintenance of germinal center reactions. with this process and may contribute to the development of autoimmunity. The interaction of B cells and a subset of T-cells known as follicular helper T-cells (Tfh cells) within structures called germinal centres, results in the selection of B cells that can produce more potent antibodies. These B cells then develop into long-lived antibody- producing cells that are responsible for immunological memory and fighting off infections. 1 . Localisation of endogenous 2 . Mouse spleen section showing T Our work in the last year has helped Roquin (red) to cytoplasmic stress follicular helper T (TFH) cells (pink) granules, distinct from P-bodies unravel fundamental several aspects in a germinal center area (IgD = (green) in 293T cells . of Tfh cell and germinal centre biology. green; PD-1 = red; CD4 = blue) .
The John Curtin School of Medical Research Annual Review 2009 29 Immunogenomics Group
http://jcsmr.anu.edu.au/org/imm/immunogenomics
Mechanisms of immunological memory
Professor Chris Goodnow Immunology Program
We bring scientists together The group discovers molecular and cellular research problems that break new ground to use cross disciplinary mechanisms and genes regulating the conceptually and clinically, and learn a methods to examine the immune response: broad range of methods and concepts from across the fields of modern genomics molecular and cellular basis • to prevent autoimmunity against self and immunology . of mechanisms used by the antigens (eg lupus, diabetes, rheumatoid immune system . arthritis, thyroiditis) One of the exciting discoveries published • to prevent uncontrolled growth of in the last year, led by PhD student and lymphoid malignancies (leukemia, clinical immunologist Dr Katrina Randall, lymphoma and myeloma) has been the identification of a new gene and protein, DOCK8, serving a critical role in Formation of durable immunological • to promote immunity and immunological the durability and persistence of immunity memories . The collections of red memory against viruses and bacteria cells are antibody producing B cells (Randall K et al 2009 Nature Immunology (immunisation and immunological responding to an immunisation 10:1283). The success of immunisation memory). within structures called germinal - one of the greatest returns on medical centres, where a survival of the We aim to answer central questions about research investment of all time - hinges fittest process selects the best the mechanisms of tolerance and immunity antibodies for long-lived production . upon the ability to establish a state of in B and T cells, and to create a collaborative immunity that persists for years or decades. Katrina Randall’s research revealed environment where the next generation of The ANU team together with colleagues at that this selection process, and the scientific leaders can establish independent resultant long-lived immunity after Oxford University, the Garvan Institute, and immunisation, involves a critical lines of research while drawing upon Cancer Research UK, used a genome-wide signal delivered by DOCK8 . The green shared expertise and resources. To achieve screen, state-of-the-art mouse molecular cells around them are other B cells . these aims, we genetics, flow cytometry and imaging tools develop and use to pinpoint DOCK8 as the key for delivering state-of-the-art signals in lymphocytes that ensure long- methods from lived immunity and antibody production. mouse and human Excitingly, these discoveries converged molecular genetics with parallel molecular genetic studies by and genomics, colleagues in the US and Europe that found biochemistry and DOCK8 mutations were also responsible for cell biology, cell a severe human immune deficiency disease, signalling, cellular illustrating the synergy between human immunology and mouse studies that has opened up by and clinical the new tools of genomics. The team is now immunology. able to use the mouse model of this disease to define the signals needed for long-lived Members of T cell immunity to viruses, and durable our group antibody-mediated immunity. pursue exciting
30 The John Curtin School of Medical Research Annual Review 2009 Infection & Immunity Group Infection and Immunity Laboratory http://jcsmr.anu.edu.au/org/imm/infimm
What happens when our immune system overreacts?
Associate Professor Guna Karupiah Immunology Program
Our research program uses mouse models ensure that virus is controlled and infection of viral infections to study both innate resolved. Although much of the expansion and adaptive immunity to infection. is due to division of antigen-specific cells, This approach enables us to establish our group (in collaboration with C. Parish strong causal relationships and map the and B. Quah) have recently demonstrated requirements for protection against viral a completely novel additional mechanism infections in a way that is not possible by which the pool of effector T cells can in humans. We are studying innate, cell- quickly enlarge. We found that antigen- mediated and antibody responses to both specific CTL transferred their T cell receptor primary and secondary viral infection with (TCR) to recipient CTL (of a different antigen the aim of determining the correlates of specificity) that, as a consequence, gained protective immunity. This is done using the antigen specificity of the donor T cell wildtype and recombinant viruses (orthopox, (Figure). The receptor transfer allowed rapid orthomyxo, herpes) in combination with expansion of virus-specific T cell clones wildtype, gene knockout, gene knockin, TCR of low frequency, and played a highly transgenic, BCR transgenic and mutant significant antiviral role, protecting the host mouse models. from an otherwise lethal infection. This finding not only provides new insight into The best correlate of long-term protective the versatility of the host response to virus, immunity conferred by effective vaccines but will also allow us to use this hitherto to date is neutralising antibody. Indeed, unknown mechanism in designing new humoral immunity to smallpox is stable and therapeutic strategies to overcome human lasts up to 75-90 years. Despite this, much disease and may lead to treatments that of the current understanding of long-lived would be beneficial in overcoming medically antibody responses is based on studies significant persistent viral infections. using non-replicating model antigens, and key aspects of humoral memory to As the outcome of an infection is dependent viruses remain elusive. We are using a well- on the interaction between viral and host established model of orthopoxvirus infection genes, we are also investigating how some in its natural host to characterise critical virus-encoded immune evasion molecules features of long-term humoral immunity subvert or dampen the host antiviral to virus. We are interested in defining response. This will not only provide a the attributes of viral antigen that elicit better understanding of the workings of the most efective antibody responses, and the immune system, but might pave the which lead to optimal long-term humoral way for utilisation of recombinant virus- immunity; with a view to the design of new encoded proteins to treat certain chronic and more efficacious vaccines. inflammatory diseases.
Another aspect of the immune response The overall aim of our research program is to critical for virus control is cytotoxic T gain a better understanding of the immune lymphocyte (CTL) function. Since for response to viral infections, which will be any given virus the host has only a small key to developing novel therapeutic and number of precursor cells, numbers of vaccination strategies to combat these cells have to increase dramatically to viral diseases..
The John Curtin School of Medical Research Annual Review 2009 31 Infection & Immunity Group Inflammation and Viral Immunopathology Laboratory
http://jcsmr.anu.edu.au/org/imm/infimm
Minimising harm from the immune response
Dr Geeta Chaudhri Immunology Program
We are examining ways to We study the host immune response to promising routes to the development of new minimise immunopathologies viral infection and the disease processes selective treatments that would minimise the that sometimes ensue as a result of damaging effects of an established infection. that can sometimes result an over-exuberant response. The host from an over-reaction of our response involves the activation of a Our current focus in this area has been on the cytokine tumour necrosis factor immune system to infection . complex network in which numerous cell types and soluble factors of the immune (TNF); expressed in both soluble (sTNF) system participate. At the site of infection and membrane (mTNF) forms. We have leukocytes are induced by these factors demonstrated that mTNF participates to migrate to the in reverse signalling, a process whereby local lymph nodes interaction with its receptor leads to the where they initiate transmission of signal in the direction an antiviral immune of the cell expressing mTNF (Figure 2). response. The The biological outcomes, resulting from resultant army of activation of this pathway, are currently activated leukocytes being elucidated in our laboratory and we then migrates to all believe it constitutes a major route through sites of infection which information transfer occurs when TNF to eradicate the receptors (TNFR) bind to mTNF. virus (Figure 1). Of the strategies used by viruses to However, the effector attenuate the host response, many are mechanisms that are directed toward interfering with TNF generated to control function, thus implicating this cytokine as an and clear virus often important player in virus-host interactions. inadvertently cause Poxviruses, including ectromelia virus, Figure 1 collateral damage to encode molecules homologous to TNFR. host tissue resulting in immunopathology Using this model, we have found that host that has serious, sometimes lethal, TNF is up regulated during infection and that consequences for the host. Pathological mTNF plays a role distinct from sTNF in the conditions such as viral pneumonia and response to infection. This is due, in part, to encephalitis are some outcomes of this the ability of mTNF to participate in reverse immunopathology. signalling. Further, virus encoded TNFR utilises the same pathways as soluble host We have directed our research effort toward TNFR to modulate immunopathogenesis, understanding the immune response to during this infection. infection with the aim of manipulating it in a manner that will minimise immunopathology We are investigating the possibility that whilst allowing resolution of infection. These recombinant virus proteins, which have studies are being carried out in parallel with been engineered by nature through Figure 2 others that attempt to reveal strategies evolution to limit the immune response and that viruses have evolved to evade or inflammation, may be used as therapeutic attenuate the host response. Together these agents to combat diseases complementary approaches are the most where inflammation and immunopathology are a problem.
32 The John Curtin School of Medical Research Annual Review 2009 Translational Research Unit
Diseases of immunity
Dr Matthew Cook Immunology Program
We are trying to understand The Translational Research Group works at parallel investigations in human subjects, the basis of three types the interface between fundamental biology where opportunities to manipulate of immune-mediated and clinical research in order to advance immunity are necessarily far more restricted. our understanding of diseases pathogenesis. disease: immune deficiency, Nevertheless, confirmation that the In this way, we hope to make progress that same mechanisms hold is essential if we hypersensitivity and will improve the diagnosis and treatment of are to make progress in human disease. autoimmunity . immune-mediated diseases. In some situations, we can test disease These diseases fall into three main mechanisms or genetic causation by categories: Immune deficiency, where direct analysis of human samples in the pathology results from failure to mount a laboratory. To this end, we are fortunate to sufficient or appropriate immune response have extensive clinical collaborators from to a pathogen, resulting in unusual around Australia, and internationally. We susceptibility to infection, hypersensitivity have recruited patients with lupus (APOSLE diseases (such as allergy), where pathology study), immune deficiency (ANZADA results from quantitative or qualitative study), atopic dermatitis, and less common aberrations in immunity to environmental immune mediated diseases, such as allergic antigens (eg pollen or foods), and bronchopulmonary aspergillosis. Recruitment autoimmunity, where pathology results for each of these studies is continuing. from immune response to host antigens. We are investigating each of these classes In the last year or two, we have made of pathology because they are all important significant progress in understanding the causes of human morbidity and mortality, cellular basis for each class of immune- and because there is significant coincidence mediated disease. In particular, partial of these forms of pathology. Specific areas deficiencies or excesses of different of investigation are primary antibody subsets of T cells can mediate immune deficiency and hyper IgE syndromes deficiency (deficiency of Th17 cells in (immune deficiency diseases), systemic lupus autosomal dominant hyper IgE syndrome), erythematosus and Sjogren’s syndrome autoimmunity (excess follicular helper T (autoimmune diseases), and regulation of cells in lupus), and allergy (partial Treg Th2 immune responses (allergy). deficiency causing Th2 deviation). With Our overall approach involves investigating this information, together with established disease mechanisms using animal models, collaborations, and very recent technical where we can achieve considerable advances, we are optimistic that significant certainty about disease mechanisms by progress can be made in unravelling the experimental manipulation of the immune complex genetic basis of these human system. These studies are combined with diseases in the next few years.
The John Curtin School of Medical Research Annual Review 2009 33 Research program Neuroscience
Program Head Professor Greg Stuart
Group Leader
Cerebral Cortex Group Associate Professor John Bekkers
Neuronal Signalling Group Professor Greg Stuart Axon Laboratory Dr Maarten Kole Brain Development Laboratory Dr Zan-Min Song Learning and Memory Laboratory Dr Clarke Raymond Neuronal Integration Laboratory Professor Greg Stuart
Synaptic Transmission Group Professor Bruce Walmsley Neuronal Network Laboratory Associate Professor Christian Stricker Synapse and Hearing Laboratory Professor Bruce Walmsley
Visual Neuroscience Group Professor Trevor Lamb
Blood Vessel Group Professor Caryl Hill
34 The John Curtin School of Medical Research Annual Review 2009 Cerebral Cortex Group http://jcsmr.anu.edu.au/org/dns/cortex
How do we smell?
Associate Professor John Bekkers Neuroscience Program
In order to understand more The delicious aroma of a mug of hot coffee This year we have begun to understand about how the brain works, is one of life’s pleasures, yet we tend to think how particular types of neurons, identified by us in earlier work, are wired up to each we are studying the area of of the sense of smell as being relatively unimportant. Part of the reason is that other to form electrical circuits in the the brain which recognises smell is regarded as a “primitive” sense, of olfactory cortex. For example, the inset in and remembers smells . more significance to the family dog than to Figure 1 shows a living brain slice with two glass recording electrodes in position, one humans, who rely much more on hearing and on a semilunar (SL) neuron, the other on a vision. In my group we are taking advantage superficial pyramidal (SP) neuron. SL and SP Figure 1 of the “primitive” nature of smell, neurons have very different shapes (black using it as a unique window into the tracings in the figure). Also shown in the operation of the brain. slice is an electrical stimulating electrode We study the olfactory cortex, (Stim) for testing electrical connections which is a simple, 3-layered brain onto the SL and SP neurons. We found region important for recognising that SL neurons receive much stronger and remembering odours. Although electrical signals from the nose than do SP neurons, an unexpected finding with little is known about how it works, major ramifications for our ideas about the the olfactory cortex is thought workings of this brain region. to construct odour images (e.g. “coffee”) from the numerous In another series of experiments, we have chemicals that are detected by the studied the connections made by a different nose when we sniff something. family of neurons, those that release the In other words, the neurotransmitter GABA. One member of this family, which we call fast-spiking multipolar olfactory cortex (fMP) neurons, can be identified because assembles sensory they contain several molecular markers (GFP, information into a PV, CB; see Figure 2). We found that fMP coherent picture of the neurons have very profuse axons (red lines in outside world – a very the figure) that are concentrated in layer II fundamental process of the olfactory cortex – precisely where the that occurs in many cell bodies of SL and SP neurons are located. brain regions. Clearly, This and other evidence indicates that fMP an understanding of neurons form powerful inhibitory connections this process is onto SL and SP neurons. In this way we are essential for making building up a circuit diagram for the olfactory sense of brain function cortex as a prerequisite for achieving a clear and dysfunction. understanding of how it works.
Figure 2
The John Curtin School of Medical Research Annual Review 2009 35 Neuronal Signalling Group Brain Development Laboratory
http://jcsmr.anu.edu.au/org/dns/neurosignal/braindev
Endothelin B receptor in brain development
Dr Zan-Min Song Neuroscience Program
Endothelin receptor B Normal brain development is regulated Recently we showed that EDNRB mutation mutation can lead to by multiple factors. We study the brain significantly reduced neuronal proliferation the congenital condition abnormalities in rats with Hirschsprung’s but increased cell death in neonatal rat disease, which is a congenital condition cerebellum and hippocampus. Furthermore, Hirschsprung’s Disease . characterised by the absence of enteric we demonstrated that these effects were ganglia and neurological anomalies. This independent of changes in the expression of disease in rats, as in human, can be caused neurotrophic factors BDNF and GDNF. These by endothelin receptor B (EDNRB) mutation. results suggest that ENDRB mediates neural proliferation and have anti-apoptotic effects in the cerebellum of the postnatal rat. Our findings will lead to better understanding of the morphological changes in the cerebellum of Hirschsprung’s disease patients with congenital EDNRB mutation.
Effects of alpha 2A adrenoceptor (AR) on neuronal development Catecholamines have been implicated in regulating neuronal maturation through various adrenoceptors. Application of alpha2 AR agonists significantly increases dendritic growth in primary neuronal cultures. We aim to determine the effects of alpha2-ARs on the development of dendritic spines, including their length and density. We will also examine the underlying molecular mechanisms, which may involve (1) cAMP / cAMP response element binding protein pathway (2) direct interaction between adrenoceptors and spinophilin, and the phosphorylation states of CREB and spinophilin. The results will contribute to the understanding of the molecular mechanisms of adrenoceptor mediated neuronal spine development.
36 The John Curtin School of Medical Research Annual Review 2009 Neuronal Signalling Group Learning & Memory Laboratory http://jcsmr.anu.edu.au/org/dns/neurosignal/learning
Mechanisms of information storage in the brain
Dr Clarke Raymond Neuroscience Program
We are studying the way Whenever we learn, changes occur in our investigated the roles of different types of that small changes in brains. Brain cells (neurones) communicate a molecular ‘sensor’, or receptor, called the individual brain cells relate via special points of contact called synapses. NMDA receptor in the induction process. We Synapses can be made stronger through have found that different subtypes of this to learning and to the repetitive activation of the connected receptor are selectively involved in triggering formation of memory . neurones, in a phenomenon called long- different durations of strengthening. We term potentiation, or LTP. The “long-term” are also investigating the role of dopamine nature of this increase in synaptic strength in this process. A second question relates to can vary from an hour to weeks or even what changes are directly responsible for years. Strengthening a synapse means that synaptic strengthening? We have discovered information passes more easily between that an increase in neurotransmitter release neurones and it is therefore believed to is important only for more persistent forms be a mechanism for making memories. of strengthening. Research of this kind will One question we have asked is what reveal specific molecular targets through triggers synaptic strengthening? In the which we can enhance or diminish different past we determined that rapid increases forms of synaptic strengthening and relate in calcium at specific locations within their effects to learning and memory. neurons would trigger strengthening for different durations. More recently, we have
Schematic diagram illustrating proposed mechanisms involved in different forms of LTP (LTP 1, 2, and 3) .
The John Curtin School of Medical Research Annual Review 2009 37 Neuronal Signalling Group Neuronal Integration Laboratory
http://jcsmr.anu.edu.au/org/dns/neurosignal
Understanding the brain neuron by neuron
Professor Greg Stuart Neuroscience Program
The Neuronal Signalling The Neuronal Signalling Laboratory Electrical signalling in dendritic spines Group is trying to understand conducts basic research on how nerve Input onto many nerve cells in the brain cells in the brain process information. the processing of information occurs onto specialised projections called This work involves recording activity by individual nerve cells in dendritic spines, which are connected to the from single nerve cells (neurons) using the brain . both electrical and optical techniques. main dendrite by a thin neck. Despite the Over the past year we have been potential importance of dendritic spines to investigating the following issues: brain function direct experimental evidence on electrical signalling in spines is lacking Changes in cell properties following as their small size (typically less than one sensory deprivation µm in diameter) makes them inaccessible One of the most amazing properties of the to standard recording techniques. In a brain is its ability to change in response to changes in the environment. This gives our world first, we have investigated electrical brains the capacity to learn and remember. signalling in dendritic spines using optical To understand this process better we have methods with voltage-sensitive dyes. investigated how changes in sensory input We find that nerve impulses fully invade influence the properties of single neurons dendritic spines without voltage loss. in the cortex. We find that a reduction in Modelling indicates that the spine neck sensory input, as might occur following nerve injury, leads to an increase in the resistance is likely to be too low to act as excitability of neurons in the cortical area a physical device to significantly modify that would normally receive this input. synaptic strength.
38 The John Curtin School of Medical Research Annual Review 2009 Synaptic Transmission Group Neuronal Network Laboratory http://jcsmr.anu.edu.au/org/dns/synapse/stricker
How the brain learns to see the future
Associate Professor Christian Stricker Neuroscience Program
We use: Our behaviour is ultimately linked to the via adrenergic (α1) and serotonin via ability of the brain to perform neuronal serotonergic receptors (5-HT ) electrophysiological recording, 2 immunohistochemistry, computation. The brain learns from past • how synaptic characteristics need to be behaviours to anticipate the future. As imaging and modelling combined precisely with the integrative an example, when we see a ball in the air, techniques to understand properties of the dendrites to optimise we estimate where it is going to land so the computational capacity of the how the brain performs high that we can catch it. How neurones and neurones. This is a little studied aspect of level neuronal computations . networks within the brain accomplish such neuronal computation and one we focus tasks is unknown. A considerable body of on in the laboratory work suggests that neuronal computation • learning and memory formation are most happens at the single cell level where likely linked to long-term changes in synaptic signals are integrated by dendrites, synaptic efficacy. However, such changes the “branches” of the neuronal tree that may limit the computational power of receive information. Whilst dendrites the synapse by reducing the range over seem to have a large capacity to influence which computation can occur. This, how single neurones compute, these are however, could pose severe limitations to by no means the only devices utilised adaptation. We investigate how to accomplish this. A largely underrated long-term and short-term changes in component that can drive neuronal synaptic plasticity interact to maintain computation is the synapse, the point of information transfer between neurones. the computational capability. To accomplish this research, we utilise My group investigates how synapses in brain a number of different techniques: modulate information transfer and shape electrophysiology of single and connected neuronal computation. We focus on the cell pairs in slices of young rodents; following three aspects: histochemistry to identify the type of nerve • how the computational properties of cells recorded; immunohistochemistry to synapses are altered by the involvement identify particular targets of calcium from of presynaptic calcium stores which, stores in the nerve terminals like channels; when activated, confer special properties imaging techniques to directly track changes to information transfer. We have found in calcium in nerve terminals; computational that several neurotransmitters have the techniques to determine membrane ability to cause calcium store release, properties and simulations to analytically among them glutamate via metabotropic investigate how information transfer is glutamate receptor (mGluR5) or affected and modulated in synthetic small neuromodulators like noradrenaline circuits of realistic nerve cells.
The John Curtin School of Medical Research Annual Review 2009 39 Synaptic Transmission Group Synapse & Hearing Laboratory
http://jcsmr.anu.edu.au/org/dns/synapse
Hearing & tinnitus
Professor Bruce Walmsley Neuroscience Program
We study the ways in which Sounds entering the ear are transformed neurons and synapses are very different the brain interprets sound, by the cochlea into trains or patterns of in the brains of congenitally deaf mice. and the changes that occur in nerve impulses, which are then relayed Auditory neurons may be more excitable, to the brain via the auditory nerve. and the normal tonotopic gradients of deafness and tinnitus . The transformation from mechanical neuronal properties are disrupted in deaf vibrations to electrical nerve impulses mice. Our experiments have also shown occurs at specialised synapses between that in normal hearing mice, exposure to the sensory ‘hair cells’ and neurons in the moderate sounds is sufficient to alter the cochlea giving rise to the auditory nerve. expression of particular proteins (such as The cochlea is arranged so that different potassium channels) in auditory neurons. regions systematically respond to different Understanding the role of neural activity sound frequencies, in a so called ‘tonotopic’ in modifying or regulating the properties organisation. This tonotopic organisation of auditory neurons and their synaptic is preserved in the brain, from the first connections is important to understanding auditory nucleus in the brainstem all the how the brain interprets sounds, and the way up to the auditory cortex. changes that occur in auditory dysfunctions such as deafness and tinnitus. The proper development and functioning of the auditory system requires auditory Our current research is aimed at nerve activity. Our experiments have understanding how the cochlea generates shown that the properties of auditory patterns of spontaneous and sound- Auditory neurons in the evoked nerve impulses, and the effect of brainstem of a mouse this auditory nerve input on the properties of auditory connections in the brain. Interestingly, one of the major theories of tinnitus is that the perception of these phantom sounds is actually generated in the brain in response to an imbalance in the activity of auditory input from the cochlea due to the dysfunction or loss of sensory hair cells. The response of the brain to a lack of input appears to result in the autonomous generation of abnormal activity or even oscillations in the firing pattern of auditory neurons. Thus, understanding the response of auditory neurons and synapses to changes in auditory nerve activity may provide important clues to the nature of disorders such as tinnitus.
40 The John Curtin School of Medical Research Annual Review 2009 Visual Neuroscience Group http://jcsmr.anu.edu.au/org/dns/visual
Photoreceptors: Response recovery, dark adaptation & evolution
Professor Trevor Lamb Neuroscience Program
My group studies the light- Understanding how light-sensitive of calibrated levels of intense illumination, sensitive rod and cone cells in the eye recover from light we measured in separate experimental runs, firstly, the ERG ‑b wave signal elicited photoreceptor cells of the We have recorded the electrical responses of individual rod photoreceptor cells from from the subject’s eye by a test flash and, eye . We have examined how the eye, using “suction pipette” electrodes. secondly, the subject’s visual threshold for these cells recover from light In these experiments we have been able to the detection of extremely dim flashes. We exposure, both in the short investigate the roles of particular proteins found that these two distinct measures of recovery of a subject’s night vision ran term (seconds) and also in through the use of transgenic zebrafish (provided by colleagues in Japan) that closely parallel to each other. Specifically, the longer term (tens of have been engineered to express proteins we were able to show a close correlation minutes) following cessation of interest. Rods that express the shut- between the electrical sensitivity of retinal rod bipolar cells and the psychophysical of illumination . off protein GRK7 (which normally occurs sensitivity of the subject’s entire visual only in cone photoreceptors) recover system. From these results we were able to In addition, we have probed from light abnormally – as expected, their conclude that the slowness of recovery of the steps that are likely to responses are less sensitive than in normal the overall human visual system following cells but, paradoxically, they are also have been involved, over intense light exposure is determined by slower. Analysis of the variable responses hundreds of millions of years, processes that occur by the stage that that are elicited by very dim flashes has the visual signals have reached the rod in the evolution of these cells . indicated that the activated light-sensing bipolar cells, i.e. before, or at, the first molecules (rhodopsin) in these rods can be synapse in the retina. shut off both by the normal GRK1 protein as well as by the added GRK7 protein. Evolution of the vertebrate eye These experiments are revealing how rod My collaborators and I have continued to photoreceptors recover from light exposure, study the evolution of the vertebrate eye. and they also help to explain the differences In conjunction with Professors S.P. Collin between rods and cones. (University of Queensland) and D. Arendt (EMBL, Heidelberg), I edited a Theme Issue of Recovery of human “night vision” the Philosophical Transactions of the Royal We have examined the very slow recovery Society B comprising 12 articles devoted of the human visual system following to the evolution of phototransduction and exposure of the eye to very intense eyes. In collaboration with S.P. Collin, I have illumination. The observed slowness of been designing experiments to test a set of recovery can be viewed as a characteristic predictions that we made recently, about after-effect of intense light exposure on how the retina is wired, about the structure the visual system, and the phenomenon is of its light-sensitive cells and about how termed “dark adaption”. In our study, we the light-sensitive proteins of different have compared the electrical responses species have diverged from each other. We recorded from the human eye (known as the have gathered material from hagfish and electroretinogram, or ERG) with the ability we are planning an investigation that will of the same human subject to detect very involve electrophysiological, anatomical and dim illumination. Following the delivery histochemical experiments on hagfish eyes.
The John Curtin School of Medical Research Annual Review 2009 41 Blood Vessel Group
http://jcsmr.anu.edu.au/org/dns/bloodvessel
Hypertension
Professor Caryl Hill Neuroscience Program
New drugs to treat high Hypertension is the major risk factor for ion channels in the cell membrane called blood pressure will be critical cardiovascular disease, the leading cause voltage dependent calcium channels of premature death worldwide. However, (VDCCs). Although 10 subtypes of these if we are to reduce the a considerable proportion of patients channels exist, only one subtype, called number of deaths due to do not respond to treatment and so the L-type channels, has been considered to be cardiovascular disease . identification of novel therapeutic targets involved in arterial contraction. In view of is an area of critical significance from both the ineffectiveness of antagonists against financial and humanitarian points of view. the L-type channels in reversing vasospasm, we have investigated whether other VDCCs An important regulator of blood pressure might play a role in cerebral arteries. are the smallest arteries and arterioles which provide the greatest resistance to In addition to the L-type channels, we blood flow and it is enhanced constriction have found evidence for the expression of of these vessels that can produce another group of channels called the T-type hypertension. Excessive constriction of VDCCs in cerebral arteries. Importantly, cerebral arteries, termed vasospasm, is also we have shown that antagonists of L-type seen in a significant proportion of patients channels are less effective in counteracting following subarachnoid haemorrhage. cerebrovascular constriction as the size of However, the effectiveness of current the artery decreases. therapeutic treatment against this life Additionally, our electrophysiological threatening condition is questionable. results confirm that the contribution Constriction of arteries depends on a rise of L-type channels to calcium current in calcium within the muscle cells of the in cerebrovascular smooth muscle cells vascular wall and coordination of the decreases with the size of the vessel of origin. contraction along the length of an artery. Our data thus provides evidence for a The major route for calcium entry into heterogeneous population of calcium vascular smooth muscle cells is through channels contributing to the function of cerebral arteries with a greater importance of the T-type channels in the smaller arteries which are the most critical determinants of blood pressure. As these channels do respond to certain classes of drugs, our results suggest that these drugs, in combination with L-type VDCC antagonists, may provide a more effective treatment for therapy-refractory cerebrovascular constriction.
42 The John Curtin School of Medical Research Annual Review 2009 Research program Structural Biology
Program Head Professor Philip Board
Group Leader
Biomolecular Structure Group Dr Marco Casarotto
Cytokine Molecular Biology Group Professor Ian Young
Membrane Physiology and Ion Channel Signaling Group Dr Louise Tierney
Molecular Genetics Group Professor Philip Board Cancer Metabolism and Therapy Laboratory Dr Anneke Blackburn Molecular Genetics Laboratory Professor Philip Board
Muscle Research Group Professor Angela Dulhunty Cardiac and Skeletal Biochemistry Laboratory Dr Nicole Beard Muscle Biochemistry Laboratory Professor Angela Dulhunty
Stem Cells and Gene Targeting Group Professor Klaus Matthaei
The John Curtin School of Medical Research Annual Review 2008 43 Biomolecular Structure Group
http://jcsmr.anu.edu.au/org/structbio/biostruct
Drug design
Dr Marco Casarotto Structural Biology Program
A challenge to the design of new drugs is to get the drugs across and Hepatitis-C (P7) and are involved in cell membranes to their target . We are examining ways to deliver different phases of the virus life cycle. We the “biological cargo” across the membranes, in an attempt to have developed a strategy that employs surface plasmon resonance techniques treat a variety of diseases . The research underway in the biomolecular to measure the affinity of a number of
structure laboratory focuses on examining antiviral drugs to these ion channels and the structural properties of biological in the case of the M2 ion channel, have A B systems with an emphasis on drug discovery used this technology to resolve the A V27 V27 and delivery. We use a diverse number mode of binding of the drug amantadine biophysical techniquesS31 such as nuclear (see diagram). magnetic resonance (NMR), surface 2. Two muscle-related proteins, the plasmon resonance, fluorescence dihydropyridine and ryanodine receptors spectroscopy andD44 molecular modelling (DHPR and RyR) play a critical role in D44 to investigate how the structure of regulating calcium concentrations in biologically-relevant molecules impact muscle cells. In skeletal muscle, we are upon their function. Several projects in the interested in how these two proteins are
D44 laboratory involve membrane-associated able to interact with each other and have systems which are challenging from a succeeded in mapping their interaction molecularD44 biology and structural aspect. site. This information paves the way for V27 Three distinct projects are described below. the development of drug therapies that S31 V27 S31 may address a number of muscle-based 1. Virions are small proteins capable of diseases. forming multimeric ion channels. They are expressed in a number of viruses 3. The delivery of biological agents into cells A B including influenza A (M2), HIV-1 (Vpu) poses one of the modern day challenges V27 V27 B of drug design. A major obstacle to this
S31 problem is the transport of molecules across the biological membrane and we Structures of the transmembrane domain of are exploring the delivery of biological the influenza FigureA M2 ion 1 channel showing the cargoes such as peptides/proteins, DNA, D44 adamantane binding sites . Key active-site RNA and drug compounds across this D44 residues are highlighted V27 (green), S31 barrier into a variety of cells. The enzyme (yellow) and D44 (orange) . (A) Side view of the glutathione transferase (GST) has been X-ray crystal structure of M2 (residues 22-46) shown to be an effective vehicle for D44 bound to amantadine (blue) [3C9J] showing an the delivery of these cargo molecules. ion-channel pore binding site and (B) Side view D44 Currently, our laboratory is involved in the of the solution NMR structure of M2 (residues V27 delivery of molecules that may hold the 18-60) bound to rimantadine (magenta) S31 V27 S31 key in the effective treatment of diabetes, [2RLF], showing a lipid-facing adamantane cancer and sexually transmitted diseases. binding pocket .
44 The John Curtin School of Medical Research Annual Review 2009
Figure 1 Cytokine Molecular Biology Group http://jcsmr.anu.edu.au/org/structbio/cytomol
Cytokine signalling in health & disease
Professor Ian Young Structural Biology Program
The three cytokines we study We are studying three hormone-like James Murphy (Walter & Eliza Hall Institute have a role in regulating proteins (cytokines; IL-3, IL-5 and GM- of Medical Research, Melbourne) have the immune response . They CSF) which regulate immune responses to revealed two different modes of receptor stimulate white blood cells infections. They stimulate the maturation activation which influence whether blood to mount a defence against and activation of white blood cells involved cell-forming stem cells undergo maturation parasites, and in asthma . in host defence against parasites and in or self-renewal in response to IL-3. In allergic asthma and may also have a role allergic inflammation, maturation is normal in leukemia. The cytokines bind to cell but the three cytokines are involved in the surface receptors and influence the growth, production of high levels of inflammatory maturation and activation state of blood cells such as basophils, eosinophils and mast cells. Our aim is to elucidate the molecular cells. By contrast, excessive self-renewal and details of the cytokine-receptor interactions defective maturation are the hallmarks of and how these interactions initiate signals leukemia and we are trying to understand across the cellular membranes. A major how oncoproteins block the maturation of focus is on the role of IL-3 in regulating blood cells induced by IL-3. We are studying allergic inflammation involving basophils, a the role of a new class of cellular regulators cell now recognised as being a key player in (microRNAs) in controlling the maturation allergic immune responses. In collaboration with Paul Foster (University of Newcastle) of inflammatory cells. Our future studies will we are studying the role of IL-3 in asthma investigate the possible involvement of the using gene-targeted mice. We have IL-3 receptor system in myeloid leukemia previously determined the 3D structure of and we have developed an important the main signalling receptor (hßc) shared by collaboration with the Fujian Medical these cytokines using X-ray crystallography. University in China which is a centre for Our recent studies in collaboration with leukemia treatment.
The John Curtin School of Medical Research Annual Review 2009 45 Membrane Physiology and Ion Channel Signaling Group
http://jcsmr.anu.edu.au/org/structbio/membrane
Molecular mechanisms of ion channel function
Dr Louise Tierney Structural Biology Program
Our understanding of ion Ion channels are known for their role Currently we are examining the extent to in electrical signalling in the brain and which GABA receptors cross-talk modulates channels is leading to insights A into the ways in which a fine balance between inhibitory and channel activity both in the control of excitatory inputs ensures normal brain neuronal excitability in the brain and in drugs work, and the brain's function. Our study of the major inhibitory GABAergic signalling in peripheral tissues. By potential to adapt to neurotransmitter-gated ion channel, the targeting the mechanism of receptor cross-
environmental change . GABAA receptor, has revealed a novel way talk, using techniques that disrupt protein- in which these ion channels alter their protein interactions, we are identifying new
electrical response. GABAA ion channel targets for medical intervention in diverse
properties are dramatically affected pathologies associated with GABAA receptors through intermolecular protein interactions including depression, cancer, asthma and and we find that these have important sperm function. consequences for the way in which many In the last year: drugs work. Further, our discovery that • we have discovered the existence of GABAA receptors are clustered in the the dynamic exchange of interaction protein-protein interactions involving membrane . Their physical association partners with GABAA ion channels alters neuronal GABA receptors that profoundly not only prevents them diffusing apart their electrical activity (termed receptor A but also underpins functional changes . cross-talk) has important implications alter the biophysical properties of the ion for understanding the brain’s enormous channel Clustered GABAA receptors generate larger, more sustained responses, particularly in potential to adapt and respond to changes • increased the understanding of how drugs response to drug potentiation . in the environment. such as benzodiazepines, neurosteroids and alcohol act to increase the activity of these ion channels and generate differential responses • we have developed a range of competitor molecules that disrupt the protein interactions of the different
GABAA receptor subtypes. In biological interference assays such molecules Extracellular impede signalling pathways in both neuronal and peripheral tissues implying that cross-talk is a general mechanism
through which GABAA receptors signal.
Intracellular
GABAA Receptor Cross-talk: Interactions between receptors increase their electrical response
46 The John Curtin School of Medical Research Annual Review 2009 Molecular Genetics Group Cancer Metabolism and Therapy Laboratory http://jcsmr.anu.edu.au/org/structbio/molgen/mgpeople/blackburn.php
Breast cancer — working to prevent & cure
Dr Anneke C. Blackburn Structural Biology Program
Dichloroacetate may prove It was first recognised in the 1930s that cells to other cytotoxic cancer drugs . useful in breast cancer cancer cells utilise glucose differently to We are investigating the use of DCA in normal cells . Normal cells use oxygen to prevention for predisposed combination with standard anti-cancer metabolise glucose for energy production, women, and may reduce the drugs, to see if their ability to kill cancer whereas cancer cells preferentially cells can be enhanced by dichloroacetate . amount of toxic anticancer metabolise glucose for the production of This could mean the dose of current drugs required under current cellular building blocks via a pathway that anti-cancer drugs could be lowered, thus treatment regimes . does not require oxygen and results in the reducing toxic side effects but without accumulation of lactic acid . Other aspects loss of effectiveness . of metabolism in cancer cells also differ from normal tissues, and these differences As part of the Molecular Genetics are yet to be exploited for therapeutic Group, we are also interested in the purposes . The Cancer Metabolism and genetic factors that contribute to Therapy Laboratory is studying the effect breast cancer susceptibility and in the of redirecting cancer metabolism on outcomes for women identified with the growth and death of breast cancer very high predisposition for developing cells . We are particularly interested in breast cancer . We are investigating dichloroacetate (DCA), an old drug that whether modifying metabolism with inhibits the anaerobic metabolism of dichloroacetate or other non-toxic drugs glucose to lactic acid . This drug has been used for many years in patients with a can prevent or delay the development rare metabolic disorder and so it is known of breast cancer in mice genetically to be safe and have minimal side effects, predisposed to developing cancer . These and therefore has potential to move mice carry a mutation in the tumour rapidly into the clinic for use in cancer suppressor gene p53 and are a model treatment . We have demonstrated that by of the multiple tumour syndrome, Li- using dichloroacetate to inhibit the ability Fraumeni Syndrome . Experiments such as of cancer cells to metabolise glucose this take several years to complete, but anaerobically to lactic acid, we are able the discovery of a low toxicity, non- to stop the growth of metastatic breast hormonal drug effective in breast cancer cancer cells both in vitro and in vivo in prevention would greatly improve the animal models . outlook and quality of life for women Dichloroacetate does not kill breast carrying mutations in breast cancer cancer cells, but may sensitise cancer predisposition genes .
The John Curtin School of Medical Research Annual Review 2009 47 Molecular Genetics Group Molecular Genetics Laboratory
http://jcsmr.anu.edu.au/org/structbio/molgen
Personalised medicine
Professor Philip Board Structural Biology Program
The glutathione transferase It has been reported that adverse drug the metabolism of anticancer drugs and to enzymes have direct impact reactions are the fifth most frequent cause influence the onset of asthma as well as on a number of human of death. Drugs that are effective in most Parkinson’s and Alzheimer’s diseases. We people but are extremely toxic in a small are currently studying the metabolism of diseases, including asthma, number of individuals cannot be used dichloroacetic acid (DCA) by glutathione Parkinson’s disease, cancer unless the patients in whom toxicity is likely transferase Zeta. DCA has been proposed as and Alzheimer’s disease . to occur can be identified. The Molecular a novel anticancer drug and has Genetics Group studies genetic differences applications in other metabolic disorders between individuals in their ability to such as lactic acidosis. breakdown and detoxify therapeutic In other studies of the glutathione transferases drugs or other environmentally derived in collaboration with the Muscle Research chemicals. In order to understand the Group we have shown that a Mu class GST significance of the genetic differences we (GSTM2-2) is a potent regulator of the utilise a variety of molecular technologies cardiac ryanodine receptor. We are currently ranging from the expression of human investigating the possibility that peptides enzymes in bacteria, X-ray crystallography derived from GSTM2-2 may be useful in to determine protein structures, and the treating life threatening heart failure. generation of gene deficient mice, (with Crystal structure of human γ-glutamyl the Gene Targeting Group), as models of We are also studying the gamma-glutamyl- cyclotransferase human disease. cyclotransferase (GGCT) family of enzymes that are involved in regulating glutathione Our work is particularly focused on the concentrations. GGCT is highly expressed Crystal structure of human γ-glutamylamine investigation of the structure and function in some tumours and we are currently cyclotransferase of enzymes that investigating the significance of this as synthesize and utilise a diagnostic tool. Because of its role in glutathione, a small regulating glutathione synthesis we are molecule found in all testing GGCT inhibitors to determine if living cells that helps to they will be suitable for the treatment of protect against foreign glutathione synthetase deficient patients chemicals and oxidative who have no specific treatment options. stress. The glutathione We have discovered that GGCTs are wide transferase (GSTs) spread in nature and are members of a new family of enzymes structural family. Other members of the exhibit a wide range GGCT family of enzymes are involved in the of genetic variability break down of blood clots in mammals and that has been shown the synthesis of antibiotic molecules in some to impact directly on micro organisms.
48 The John Curtin School of Medical Research Annual Review 2009 Muscle Research Group Cardiac and Skeletal Biochemistry Laboratory http://jcsmr.anu.edu.au/org/structbio/muscle
Muscle contraction & the regulation of movement
Dr Nicole Beard Structural Biology Program
Out team investigates the The Cardiac and Skeletal Biochemistry 2. Investigating how changes in store load mechanisms by which the Laboratory investigate how control of the or in RyR function lead to heart failure. skeletal muscle calcium luminal calcium store deep inside a muscle Heart failure is a complex multimodal cell leads to muscle contraction. Muscle disorder, affecting two per cent of the binding protein calsequestrin contraction occurs due to a cascade of adult population at one time in their plays a role in controlling events and relies on calcium release from life. Heart failure is characterised by muscle contraction . luminal stores. The four main cogs in the disturbances of the luminal calcium store luminal calcium signalling pathway are and alterations in how the RyR releases the calcium binding protein calsequestrin calcium. We are investigating how cellular (CSQ), the ryanodine receptor (RyR) calcium changes which occur in heart failure release channel, and two linking proteins, alter the calcium stores ability to handle triadin and junctin, which bind CSQ to calcium and are defining how these the RyR. Control of the luminal calcium effects translate into changes in RyR store in muscle is vital; disturbances in calcium release. the process can lead to potentially fatal 3. Understanding how chemotherapeutic skeletal and cardiac conditions, including agents cause store calcium disturbances malignant hyperthermia, inclusion-linked and toxicity the heart. Anthracyclines skeletal myopathy and heart failure. Despite are highly effective chemotherapeutic their essential role in skeletal muscle and agents used to treat leukaemia and the heart, the functional and structural breast cancer. Side effects of treatment interactions between the luminal calcium with anthracyclines include severe signalling proteins that contribute to muscle cardiotoxicity and sudden cardiac death. function are poorly understood and underlie We are investigating how anthracycline the broad aim of our research. treatment changes the function of proteins in the luminal calcium signalling In collaboration with the Muscle Research pathway and how these changes result in Group, we are pursuing three main the cardiotoxic side effects. research themes.
1. Determining how communication between proteins in the luminal calcium store facilitates skeletal muscle contraction. Communication between the skeletal isoforms of CSQ and RyR is a key determinant of skeletal muscle contraction and essential for normal calcium signalling. We use a biochemical approach to uncover the protein binding partners and specific interaction sites which support this communication.
The John Curtin School of Medical Research Annual Review 2009 49 Muscle Research Group Muscle Biochemistry Laboratory
http://jcsmr.anu.edu.au/org/dmb/muscle
Muscle receptor physiology
Professor Angela Dulhunty Structural Biology Program
Understanding calcium The Muscle Research Group studies SR. EC coupling in the heart depends on RyR signalling in muscles molecular interactions between two activation by calcium ions that enter through will ultimately lead to calcium ion channels, that underlie the DHPR ion channel. This process in the calcium signalling in muscle and important heart is regulated by the muscle specific improvements in drugs for associated proteins that modify their glutathione transferase (GSTM2), a process treating muscle disorders, activity in skeletal muscle and in the heart. that has considerable therapeutic potential. In including myopathies and The two calcium ion channels are the marked contrast to the heart, EC coupling in heart disease . dihydropyridine receptor (DHPR) calcium skeletal muscle does not depend on external channel in the surface calcium. Instead, a depolarisation-dependent membrane and the signal is transmitted from the DHPR to the control O ryanodine receptor RyR by conformational coupling between the (RyR) calcium release two proteins. C channel in the internal β 1nM 1a subunit Mutations in the RyR, DHPR, calsequestrin, sarcoplasmic reticulum triadin and junctin disrupt calcium signalling (SR) calcium store. The in skeletal muscle and the heart and cause 10pA washout 500ms function of these ion skeletal myopathies and heart disease, channels is strongly both of which are often lethal. The Muscle influenced by associated Research Group is currently studying the proteins that interact Ion current recording flow during opening factors that set RyR channel activity and the with each other and with that RyR inside (O) and closing (C) of a single RyR1 channel calcium load within the SR store, including protein incorporated into an artificial the internal calcium store formed by the RyR regulation by the DHPR α1S and β1a lipid bilayer . The opening of the channel is sarcoplasmic reticulum (SR). The associated subunits and by calsequestrin, triadin, increased by very low concentrations proteins include the SR transmembrane junctin and GSTM2. We are examining the of the recombinant ß subunit of the 1a proteins triadin and junctin and the calcium functional changes introduced by mutations DHPR (middle trace) . This interaction binding protein calsequestrin. These DHPR or protein modifications that disrupt calcium between RyR1 and the DHPR ß1a subunit supports our current hypothesis that the and RyR are essential for movement and signalling and lead to myopathies and heart
ß1a subunit is intimately involved in the EC heart beat which are initiated by excitation- disease. We are also examining structural coupling process . contraction (EC) coupling. The EC coupling changes associated with disease mutations process is broadly defined as the signal in the protein segments, in collaborations transduction process that links an action with the Structural Biology and Molecular potential to contraction, but more narrowly Genetics Groups. The long term goal of encapsulates the processes that intervene our research is the rational design of drugs between depolarisation of the surface that might help alleviate the symptoms of membrane and calcium release from the skeletal and cardiac muscle disorders.
The active segment of the GSTM2 segment responsible for stabilising the activity of the cardiac RyR . Alpha helix 6 is essential for the stabilising action of the GST .
50 The John Curtin School of Medical Research Annual Review 2009 Stem Cells & Gene Targeting Group http://jcsmr.anu.edu.au/org/structbio/genetarget
Gene targeting & transgenics: Creating mice with a pre-determined genetic makeup
Professor Klaus Matthaei Structural Biology Program
By studying mice with a A major aim of modern biology is to injected cells can contribute to the testis, predetermined, controlled understand how genes function during the breeding of a chimæra with a normal set of genes, we will gain normal development and importantly, mouse gives rise to offspring carrying the during disease. However, it is often genes of the modified stem cell (including valuable insights into a impossible to perform studies directly in the the mutated gene). In this way animals are myriad of human disease human and it is therefore easier to work generated that are identical to the original conditions, including asthma with a more manipulable system such as the mouse strain except that the function of and cancer . mouse. Since natural mutations occur in a a single gene has been deleted thereby serendipitous manner, i.e. by chance; to find allowing the study of the loss of this gene a mutation in mice that mimics a particular in vivo. human disease is difficult. It is now possible, Similarly, it is also possible to add new genes given the knowledge of the nucleotide into the ES cells resulting in “transgenic” sequence of a gene, to make changes to mice that now have genes that are the corresponding endogenous gene of an overactive or expressing a protein never embryonic stem (ES) cell and produce a previously seen in a mammal. For example mouse that carries a desired mutation. This the mice in the Figure are expressing a green procedure is called gene targeting. fluorescent protein (EGFP) cloned from a Gene targeting involves the use of jellyfish. These mice allow us to transfer recombinant DNA technology to modify a green cells into normal mice and trace their cloned gene (usually to stop its function). every move. At the same time, ES cells isolated from Gene targeted and transgenic mice therefore an early mouse embryo (a blastocyst) are allow the ability to study the function of cultured and the modified a cloned gene in the context of the whole gene is introduced into the mammal by creating mutant mice modified ES cells in a manner where for specific genes. We have generated a the normal gene is replaced series of different mouse mutants that are by the mutated gene. Under at different stages of investigation including a microscope the modified ES mouse models of asthma, gut allergy, nerve cells are then micro-injected re-generation, parasite-host relationships, into another blastocyst and hypertension, wound healing, drug de- the ES cells become integrated. toxification, muscle diseases and cancer. These “combination” blastocysts are re-implanted Importantly we are developing techniques into pseudo-pregnant mice with which the gene targeted or transgenic and give rise to live chimæric genes can be turned on and off at will; offspring that consist of the allowing complete control of gene modified injected cells as well expression in all tissues to closer mimic as the normal cells. Since the human disease.
The John Curtin School of Medical Research Annual Review 2009 51 Research program Translational Medicine
Program Head Professor Julio Licinio
Group Leader
Translational Medicine Group Professor Julio Licinio
Pharmacogenomics Group Professor Ma-Li Wong
52 The John Curtin School of Medical Research Annual Review 2009 Translational Medicine Research Group http://jcsmr.anu.edu.au/org/trans/licinio.php
The interface between obesity and depression
Professor Julio Licinio Translational Medicine Program
Our studies have shown We have developed a broad range of weight regulation and for the optimal that leptin replacement translational research efforts related to functioning of endocrine organs, including can reverse morbid obesity obesity, depression and their interface . the brain . Our group has shown that leptin and associated conditions . The head of the group, Professor Julio increases gray matter in adult human Strategies aimed at Licinio, has 210 indexed publications, with brain and that functional MRI responses decreasing leptin resistance a sum of citations of 8,072, representing to food cues vary dramatically in the an average of 38 .44 citations per item presence and absence of leptin . In a child might therefore prove to be and an h-index of 42 . Over 30 of those with leptin deficiency, we documented useful in the treatment of publications are in the field of human major changes in neuropsychological obesity . leptin research . Our contributions to performance after leptin replacement . In the understanding of the biology of summary, our studies revealed that leptin human leptin include the discovery of replacement reverses fully established the pulsatility of human leptin and the morbid obesity and its metabolic, discovery of its tight coupling with the endocrine, and central nervous system rhythms of other hormones, such as those consequences . We conclude that common of the hypothalamic-pituitary-adrenal, and complex obesity is a state of leptin reproductive, and thyroid axes . In 1998, resistance . Strategies aimed at decreasing we started a line of work with a Turkish the resistance to leptin and enhancing family that has a missense mutation in leptin-mediated signaling should be the leptin gene, resulting in the same considered for the treatment of obesity . truncated leptin peptide as that of the Our work also showed that obesity in ob/ob mouse . This project started as a the absence of leptin is associated with Patient before replacement with unique USA Food and Drug Administration a different phenotype than that of recombinant methionyl human leptin at age 5y1m and during treatment at (FDA) – industry – NIH partnership obesity associated with hyperleptinemia . age 7y2m . Before treatment, the that established the first endocrine In the former there is hypogonadism patient's weight was 47 0. kg (above the replacement treatment of a genetic form but not pronounced cardiovascular and th 97 percentile for that age), his height of obesity in adults . Work in this area metabolic morbidity . In contrast, the was 109 cm (at the 50th percentile), had shown that the obese who are not latter is characterised by metabolic and and his body mass index was 39 6. kg/ m2 (above the 97th percentile) . After leptin deficient have excessive amounts of cardiovascular sequela in the context 25 months under leptin replacement leptin, with further leptin administration of normal reproductive function . The treatment, his weight decreased to 33 7. being of limited value . Our line of research hypothesis that the cardiovascular and kg (at the 97th percentile), his height on monogenetic obesity caused by leptin metabolic complications of obesity are was 119 cm (at the 25th percentile), and his body mass index decreased to deficiency demonstrates that the leptin mediated at least partially by leptin should 23 8. kg/m2 (above the 97th percentile) . pathway is crucial for human body therefore be tested .
The John Curtin School of Medical Research Annual Review 2009 53 Pharmacogenomics Group
http://jcsmr.anu.edu.au/org/trans/wong.php
The pharmacogenomics of major depressive disorder
Professor Ma-Li Wong Translational Medicine Program
We continue to use a Major depressive disorder (MDD) is a national Antidepressant drugs were discovered multidisciplinary approach public health issue in Australia. It is a highly by serendipity more than fifty years ago disabling chronic common complex disorder and the understanding that these drugs to understanding the of unknown causes. A triad of symptoms act acutely through monoaminergic treatment of the clinical characterises MDD: low or depressed mood, neurotransmission has provided the symptoms of depression with anhedonia and low energy. Up to 17 per foundations for the classical monoamine/ cent of the population experience MDD at biogenic amine hypothesis of depression. antidepressant medication . some point during their lifetimes. Our group This hypothesis is currently thought has focused on the understanding of the to be inadequate to explain why any mechanism of actions of antidepressants and given antidepressant treatment must be the pathophysiology of MDD. taken continuously for weeks to achieve treatment response. It is still unclear how antidepressants act to improve the clinical symptoms of MDD. During 2009, pharmacogenomics data generated in our A) B) lab provided evidence suggesting that the cGMP signaling cascade warrants further investigation for its involvement in MDD and antidepressant action. Cyclic GMP signaling cascade in the brain and emergent data support the role of NO/cGMP signaling in MDD: 1) cGMP signaling components are expressed in the brain regions implicated in MDD and 2) potential role of cGMP signaling in the pathophysiology of major depressive disorder and the antidepressant treatment response, including the role of phosphodiesterases. Our pharmagenetic and genetic efforts Transcriptional patterns within heart and brain. focused in resequencing genes in pathways relevant to MDD (ABCB1, SLC6A2, A) Cluster analysis of 17 non-specific genes with sustained activation in both ventricles after LPS ip . In each treatment group, squares coloured in black or dark red represent lower mRNA SLC6A3, CRHR1 and NTRK2). While our intensity whereas squares coloured in bright red represent stronger up-regulation after neuroimmunology studies have focused on administration of LPS . These genes can be classified according to their biological process as elements common to central and peripheral follows 1) Immune, inflammatory and/or acute phase response: Reg1a, Reg3b, Pap, Spp1, inflammatory response (see figure). C1s, Il1b, S100a8, Timp1, Cfb, Ptgs2, Ccl3, Ccl2, Reg3g; 2) Intracellular signaling: Pdk4, Jak2, We will continue to develop the lines Aldh1a2; 3) DNA binding/transcription factors: Cebpd, Cebpb; 4) Lipid catabolic process: of research detailed above. Our future Pla2g2a; and 5) Microtubule process/movement: Tuba1c . Highlighted transcripts (Ptgs2, Ccl2, Cebpd) were also increased within the brain . directions also include the understanding of the interface between stress, antidepressant B) Cluster analysis of 9 genes activated in the heart and the brain . These genes can be treatment and obesity. These studies are classified according to their biological process as follows1) Immune, inflammatory and/or a natural progression of our previous acute phase response: Il1a, Ptgs2, Ccl2, Cxcl1, Cxcl10, Nfkbia; 2) DNA binding/transcription work focused on the metabolic aspects or factors: Cebpd, Nfkbia; and 3) Ion binding: Lcn2 . consequences of MDD.
54 The John Curtin School of Medical Research Annual Review 2009 Australian Phenomics Facility www.apf.edu.au
bone deformities, infectious diseases, cancer and cardiovascular disease.
Grant funding for the APF infrastructure service was primarily from the Federal Government’s National Collaborative Research Infrastructure Strategy (NCRIS) and for 2009 this was $1,626,900 within a total budget of $2.58M. The APF also works closely with other NCRIS funding recipients, including the Atlas of Living Australia (CSIRO) and the Australian Plant Phenomics Facility (ANU and University of Adelaide), Located in the Hugh Ennor Building at specifically on data management and ANU, The Australian Phenomics Facility bioinformatics. (APF) is the national service organisation within JCSMR for producing recessive Total APF staff numbers during 2009 were mouse models, and providing associated 17, including staff from APN administration genomic and phenotyping services. (hosted by ANU), the APF Scientific Programs Team, the Australian Phenome Bank team Researchers use the APF’s large scale and genomics staff. research infrastructure to investigate a range of biological questions, and to better Australian Phenome Bank understand the genetic foundation for Within the APF is the Australian Phemome human disease conditions. Bank (APB) – a physical and electronic repository for all mouse strains in Australia, During 2009 the APF extensively funded by the NHMRC and NCRIS. supported the research program of the Immunogenomics Laboratory (IGL), with In 2009, a total of 162 strains were key research projects being undertaken for cryopreserved, and the information for 310 the Wellcome Trust (UK), and the National strains from around Australia were recorded Institutes of Health (US) within JCSMR. in the APB database. The APB received In addition, the APF supported a number a further two years of funding from the of research groups around Australia (see NHMRC in late 2009, and released a new below) working on a range of projects such website and operational software for users as muscular dystrophy, gastrulation and of the services to access information and the organogenesis, gastrointestinal diseases, services. See www.apb.org.au cont.
The John Curtin School of Medical Research Annual Review 2009 55 Australian Phenomics Facility
China Australia Centre for Other Highlights for 2009 Phenomics Research In May 2009, the APF hosted a translational The APF also supports the work of the China phenomics workshop, attended by clinicians Australia Centre for Phenomics Research and medical researchers from around the (CACPR) which is funded by Australian and country. The intent of the workshop was to Chinese governments, and was formally discuss future directions for the phenomics opened by ANU Vice-Chancellor Professor research community and how this translates Ian Chubb and Chinese Academy of Sciences into human disease research and outcomes. President Lu Yongxiang in 2008. During the federal budget address of 2009, CACPR studies alterations in the genome it was announced that a further $15M code that lead to increased resistance to was allocated to the Australian Phenomics influenza and other infectious diseases. Network, with $5.6M to the APF over the Chinese researchers from Beijing Institute of course of four years. This provides for new Biophysics are currently seconded at JCSMR platforms and technologies, involving the to carry out this research . development of next generation sequencing and bio-informatics, to be developed in The Australian Phenomics Network conjunction with the Biomedical Resource The Australian Phenomics Facility Facility (BRF) and with investment from Bio- works with nine other medical research Platforms Australia Pty Ltd. institutions that together with the APF make up the Australian Phenomics Network In October 2009 the APF and the Beijing (APN). This grouping provides access to Genomics Institute (BGI) agreed to world class infrastructure and facilitates collaborate in the area of Next Generation international research collaborations on the Sequencing to improve the ability to identify mouse and human genomes. See http:// causative mutations in the mouse genome www.australianphenomics.org.au/index.htm for human disease traits.
56 The John Curtin School of Medical Research Annual Review 2009 The Australian Cancer Research Foundation Biomolecular Resource Facility
http://brf.jcs.anu.edu.au
with important health, agricultural and environmental applications.
High Throughput Sequencing High throughput DNA sequencing is transforming biological (biomedical, environmental and agricultural) research from the science of single molecules/ organisms to a systems-wide science. High Throughput DNA sequencing has become the platform of choice for a great variety of applications including transcriptome The time it takes to map a single The Australian Cancer Research analysis, comparative genomics, de-novo human genome could be radically Foundation Biomolecular Resource and re-sequencing projects, epigenomics reduced thanks to two new next Facility (ACRF BRF) provides access to and mutation detection. generation DNA sequencers that were cutting edge services and equipment in unveiled at JCSMR . Technology and DNA preparation pipelines genomic and proteomic technologies to used in high throughput DNA sequencing Pictured from right to left are: researchers at JCSMR and other Schools are radically different to those used • Ms Stephanie Palmer, Manager ACRF, at ANU, as well as the broader regional Biomolecular Resource Facility JCSMR in traditional Sanger sequencing. The scientific community. The facility offers • Professor Arthur Georges, Dean of sequencing pipeline used in next generation core services including Sanger Sequencing, Applied Science (UC) • Dr Liz Dennis, sequencing involves four steps. Chief Research Scientist (CSIRO Plant High Throughput DNA Sequencing, Industry) and • Professor Frances Microarray services, Peptide Synthesis, 1. Break large strands of DNA into smaller Shannon, Director JCSMR (ANU) . Mass Spectrometry, Tetramer Synthesis and fragments. Chromatography and Antibody Purification. 2. Isolate DNA, attaching adapters to the ends of DNA and then affixing DNA 2009 was an exciting year for the BRF, with fragments to beads or glass slides and the acquisition of two high throughput DNA amplifying the single DNA fragments. sequencers – an Illumina GAIIx and a Roche GSFLX. Funding for the equipment was from an ARC-LIEF grant jointly submitted cont. by ANU, The University of Canberra, CSIRO Plant Industry and CSIRO Entomology as well as financial contributions from each organisation. The sequencers are housed in the ACRF BRF and are available for use by researchers from all institutions. These sequencers will play an important role in advancing cutting-edge research
The John Curtin School of Medical Research Annual Review 2009 57 Australian Cancer Research Foundation Biomolecular Resource Facility
3. Determine the fragment sequence peptides that have proven difficult to make visualised either using luciferase or by conventional means. fluorescence reporting directly detected by a CCD camera. Successful peptide synthesis requires a 4. Perform automated data quality near 100 per cent completion of both assessment and sequence assembly to the deprotection and coupling steps of reconstruct the original DNA sequence. the synthesis process. Optimal reaction conditions require a fully solvated peptide- Traditional sequencing involves the more polymer matrix to allow efficient reagent time consuming process of preparing libraries of cloned DNA fragments and penetration. Using traditional SPPS sequencing via electrophoresis, replacing technologies, difficult peptides tend to steps 1 – 3. form secondary structure aggregates during the addition of the 6 – 12th residues. These Data from high throughput sequencing aggregates are not able to form during is produced in a different way, and at microwave assisted synthesis, because unprecedented levels, requiring very high- the N -terminal amine group and peptide end bioinformatic tools and computational backbone are polar, and are constantly trying capabilities for meaningful interpretation. If a traditional Sanger sequencer is run to align with the alternating electric field for 24 hours a day, it can only read 1,900 of the microwave, thus allowing efficient strands at a length of 650 bases. This reagent penetration in the deprotection and results in 1.4 megabases of sequence data. coupling steps, resulting in higher repetitive High throughput DNA platforms can read yields. It is these higher repetitive yields that 1 billion strands in parallel at a length of dramatically improve product purity, and 2x100 bases, creating 200 gigabase pairs of increase the success of producing long or sequence data per run (8 day period). difficult peptides. New Peptide Synthesiser Professor Christopher Parish was awarded ANU funds for a Liberty Microwave Assisted Peptide Synthesiser to be housed in the ACRF BRF. This automated peptide synthesiser, released in 2005, is the only machine currently available for performing solid phase peptide synthesis (SPPS). Microwave technology is superior as it increases the rate of success when attempting to produce long peptides, or
58 The John Curtin School of Medical Research Annual Review 2009 Staff & Student Achievements Degrees, Prizes & Awards
A major strategic goal of JCSMR is to provide outstanding training and mentoring for medical researchers of the future. The majority of our academic staff supervise post-graduate scholars through their studies leading to Honours, Masters and PhD degrees.
JCSMR staff and students continue to be honoured and acknowledged through awards and prizes presented by local, national and international organisations.
The John Curtin School of Medical Research Annual Review 2009 Degrees 2009
Congratulations to our students who graduated in 2009
Esther Ng and Elissa Sutcliffe
PhD Degrees Awarded in 2009 Raymond Sammut Incorporating Regional Context into Pairwise Stephanie Laura Day Alignments of Biological Sequences Evaluation of Interferon Response and Activity for Effective Vaccine Therapy Nicholas Simpson Follicular Helper T Cells in Systemic Damian Francois Jaccoud Lupus Erythematosus Diversity Arrays Technology (DArT) in a Model Plant and Animal Shweta Singhal Regulation of the Cellular Localisation of the Mouse Michelle A . Linterman Usp15 Deubiquitylating Enzyme Roquin Controls Germinal Center Formation and Tolerance Yovina Sontani Analysis of the Events Leading to T Cell Leukaemia in Melanie J . Morris Ikzfi plstc/+ Mice Cellular Uptake of Glutathione Transferase Proteins: Cellular Mechanisms and the Role of Elissa L . Sutcliffe Protein Structure Coordinated Changes in Chromatin Composition Accompany Inducible Gene Transcription in Esther Mei Ther Ng Human T Cells The Biological Role of Membrane Tumour Necrosis Factor in Inflammation and Infection Han Shen Tae In Vitro Investigation of the Multi-Faceted SPRY2 Ivan K . H . Poon Domain in the Skeletal Type Ryanodine Receptor The Role of Histidine - Rich Glycoprotein in Necrotic Cell Clearance and Regulation of Zuopeng Wu Degradative Enzymes T Cell Deficiency Resulting from Aberrant pre-mRNA Alternative Splicing caused by Novel Splicing Silencer hnRNP LL in an ENU Mutant Mouse Stain Thunder
Honours Degrees Awarded Han Shen Tae, in 2009 Marco Casarotto and Elissa Sutcliffe • Laura Beaton • Robyn Rebbeck • Chantelle Boland • Erin Sendall • Jessica Fitch • Lee Kuan Ter • Daniel Hu • Elize Wium • Yogesh Jeelall • Saul Newman • Neha Pal Zuopeng Wu, Yovina Sontani, Ivan Poon, Melanie Morris and Shweta Singhal
60 The John Curtin School of Medical Research Annual Review 2009 Prizes & awards 2009 Staff and Students Honours, awards and prizes acknowledging the achievements of External awards our staff and students during 2009
Ms S . Addis Oral Presentation Prize: Australian Society for Medical Research Young Investigator’s Forum, Canberra Region Annual Scientific Meeting, Canberra, ACT Mr J .A . Altin Professor Philip Board Presentation prize, ‘Reduced regulatory T cell frequency establishes a Th2 bias and can drive selective allergic disease’, ACT/NSW Australasian Society for Immunology Annual Retreat, Bowral, NSW Travel fellowship to attend the 2009 RIKEN Summer School, Yokohama, Japan Australian Academy of Science Award to attend the Meeting of Nobel Laureates, Lindau, Germany in 2010 Professor P . Board 2009 Asian Pacific Scientific Achievement Award from the International Society for the Study of Xenobiotics Mr G . Chen AusAID Australian Leadership Award Scholarship Mr J . Feng Student Poster Prize: Genetics Society of Australia Annual Conference, Brisbane, QLD
Ms H . French Professor Chris Goodnow Ruth Gani Travelling Fellowship Professor C .C . Goodnow, Elected Fellow of The Royal Society, the prestigious UK and Commonwealth Academy of Science Dr M . Gustiananda Endeavour Research Fellowship for 2010 Dr M . Kole Paxinos-Watson Prize for most significant paper published by an ANS member, Australian Society for Neuroscience Annual Meeting, Canberra, ACT Ms I . Kuo National Heart Foundation of Australia Travel Grant American Physiological Society Caroline tum Suden Professional Opportunity Award Dr Marsia Gustiananda Ms H . Lindsay Student Oral Presentation Prize: Genetics Society of Australia Annual Conference, Brisbane, QLD Mr J . Luo NHMRC Postgraduate Scholarship from 2009 to study in the Molecular Systems Biology Group with Dr R . Williams Professor C . Parish Australasian Society for Immunology Gordon Ada Orator Dr G . Paz-Filho International Society of Endocrinology Travel Award to attend the 14th International Congress of Endocrinology 2010, Kyoto, Japan
Oscar Luo
The John Curtin School of Medical Research Annual Review 2009 61 Prizes & awards - external 2009
Professor G . Stuart Paxinos-Watson Prize for the most significant neuroscience paper published by a full member of the society in 2008, Australian Society for Neuroscience, Canberra, ACT Mr R . Sun American Association for Cancer Research Scholar-in-training travel award ($1,000 USD) for attendance at the AACR special conference ‘Metabolism and Cancer”, La Jolla, CA, US Mr V . Tahiliani Travel bursary to attend the 10th Federation of Immunological Societies of Asia-Pacific Advanced Immunology Training Course, Tangalooma Island Resort, QLD Ms C . Teh Australasian Society for Immunology Travel Bursary to attend 39th Annual Scientific Meeting of the Australasian Society for Immunology, Gold Coast, QLD Travel bursary to attend the 10th Federation of Immunological Societies of Asia-Pacific Advanced Immunology Training Course, Tangalooma Island Resort, QLD Dr L . Tze Australasian Society of Immunology international travel award to attend the 2nd European Congress of Immunology, Berlin, Germany Dr C .G . Vinuesa 2009 Australian Academy of Science Gottschalk Medal for research in the medical sciences by an early-career researcher Dr S . Weiss Cardiac Society of Australia and New Zealand Award Dr S .E . Wölfle American Physiological Society International Early Career Physiologist Travel Award Dr Z . Wu Travel Scholarship to attend Keystone Symposium ‘Human Immunology and Immunodeficiency’, Beijing, China Mr M . Yabbas Travel bursary to attend the 10th Federation of Immunological Societies of Asia-Pacific Advanced Immunology Training Course, Tangalooma Island Resort, QLD
Dr Steven Weiss Dr Stephanie Wölfle
62 The John Curtin School of Medical Research Annual Review 2009 Prizes & awards 2009 Staff and students Awarded by JCSMR & ANU
Dr Julia Ellyard ACRF Biomolecular Resource Facility Team Ms S . Palmer, Dr S . Ohms, Dr P . Millburn, Dr K . Zhang, Ms A . Higgins, Dr K . Peng, Mr C . McCrae, Mr S . Moore and Mr K . McAndrew - The Vice-Chancellor’s Award for Innovation & Excellence in Service Quality Dr A .C . Blackburn College of Medicine Biology and Environment Fellowship Assistance Award $20,000 for 2010 Professor S . Cory The Curtin Medal Dr A . Ellis ANU Office of the Vice-Chancellor Travel Grant Dr J . Ellyard The Dewar Milne Prize in Immunology: Most significant research in the field of immunology during a doctoral candidature at JCSMR Ms R . Hewawasam Vice-Chancellor’s HDR travel grant to attend a Gordon Research Conference in Boston, MA, US Dr J . Letzkus The Frank Fenner Medal: Most outstanding PhD thesis submitted at JCSMR during 2008 Mrs A . Prins Vice-Chancellor’s Award for Community Outreach Professor Suzanne Cory Dr D . Rangasamy College of Medicine Biology and Environment Fellowship Assistance Award $20,000 for 2010 Dr I . Sakala The Alan and Elizabeth Finkel Prize for 2008 Dr C .J . Simeonovic The Australian National University Staff Medal for 25 years service
Dr Elizabeth Finkel with Dr Isaac Sakala ACRF Biomolecular Resource Facility Team with ANU Vice-Chancellor Professor Ian Chubb
The John Curtin School of Medical Research Annual Review 2009 63 64 The John Curtin School of Medical Research Annual Review 2009 Visitors to JCSMR & Research Collaborations
Staff and students of JCSMR continue to enjoy close collaborative ties with colleagues across Programs within the School, and with other scientists at ANU. JCSMR researchers also enjoy close scientific association and collaboration with colleagues throughout Australia and the world. Some of these collaborative research ventures are listed here. In addition, we have the pleasure of welcoming visitors from local, national and international universities and research institutes who come to JCSMR to present seminars or work on collaborative research projects within our laboratories.
The John Curtin School of Medical Research Annual Review 2009
The John Curtin School of Medical Research Annual Review 2009 65 Visitors 2009 We have welcomed colleagues from Australia and overseas into JCSMR throughout 2009, to share their research findings or to carry out research projects in JCSMR laboratories in collaboration with JCSMR staff and students .
Mr M .N .M . Alkhreyef Professor A . Craig King Abdullah Aziz Centre for Science & Technology, Molecular and Biochemical Parasitology Group, Riyadh, The Kingdom of Saudi Arabia Liverpool School of Tropical Medicine, Liverpool, UK Professor G . Augustine Dr G . Drew Department of Neurobiology, Duke University Medical Pain Management Research Institute, University of Centre, Durham, NC, US Sydney, Sydney, NSW Professor B . Balleine Dr E . Fletcher Behavioural Neuroscience Laboratory, Brain and Mind Visual Neuroscience Laboratory, University of Research Institute, University of Sydney, Sydney, NSW Melbourne, Melbourne, VIC Associate Professor T . Biden Professor R . Foster Diabetes Signalling Unit, Garvan Institute, Sydney, NSW Nuffield Laboratory of Ophthalmology, University of Associate Professor P . Bird Oxford, Oxford, UK Department of Biochemistry, Medicine, Nursing and Dr M . Frese Health Sciences, Monash University, Melbourne, VIC Faculty of Applied Science, University of Canberra, Dr J . Bourne Canberra, ACT Australian Regenerative Medicine Institute, Monash Professor J . Gamble University, Melbourne, VIC Vascular Biology Group, Centenary Institute, Dr R . Bryson-Richardson Sydney, NSW Australian Regenerative Medicine Institute, Monash Professor S . Gerondakis University, Melbourne, VIC Intracellular Signalling and Gene Expression Dr M . Cahill Laboratory, Burnet Institute, Melbourne, VIC School of Biomedical Sciences, Charles Sturt Professor T . Gonda University, Wagga Wagga, NSW Molecular Oncogenesis Laboratory and Diamantina Dr M . Cavazzini Institute, University of Queensland, Brisbane, QLD Department of Pharmacology, Oxford University, Professor J . Götz Oxford, UK Alzheimer’s and Parkinson’s Disease Laboratory, The Professor D . Chalmers Brain and Mind Research Institute, University of Sydney, Sydney, NSW Centre for Consciousness, Research School of Social Sciences, ANU, Canberra, ACT Professor M . Good Dr N . Cherbuin Molecular Immunology, Queensland Institute of Medical Research, Herston, QLD Centre for Mental Health Research, ANU, Canberra, Dr Michael Cahill ACT Professor G . Grau Professor M . Christie Discipline of Pathology, School of Medical Sciences, The University of Sydney, Sydney, NSW Neuropharmacology Laboratory, The Brain and Mind Research Institute, University of Sydney, Sydney, NSW Dr E . Hamilton – Williams Dr S . Cooper Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, US Paediatrics and Child Health, Children’s Hospital at Westmead, Westmead, NSW Dr R . Hannan Dr A . Coward Growth Control Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC The School of Computer Science, ANU College of Engineering and Computer Science, ANU, Canberra, ACT
66 The John Curtin School of Medical Research Annual Review 2009 Professor Rajiv Khanna
Ms A .K . Hansen Dr K . Lokuge Department of International Health, Immunology National Center for Epidemiology and Population and Microbiology, University of Copenhagen, Health, ANU, Canberra, ACT Copenhagen, Denmark Professor C . Mackay Professor S . He Immunology Program, Garvan Institute of Medical Institute of Biophysics, Chinese Academy of Sciences, Research, Sydney, NSW and Faculty of Medicine and Beijing, China Faculty of Science, The University of New South Professor W . R . Heath Wales, Sydney, NSW Department of Microbiology and Immunology, The Professor A . Mackay-Sim University of Melbourne, Melbourne, VIC National Adult Stem Cell Research Centre, Eskitis Professor M . Horne Institute for Cell and Molecular Therapies, Griffith University, Nathan, QLD Brain Injury and Repair Group, Howard Florey Institute and University of Melbourne, Melbourne, VIC Professor R . Maleszka Professor G . Housley Molecular Genetics and Evolution Group, Research School of Biology, ANU, Canberra, ACT School of Medical Sciences, and Translational Neuroscience Facility, University of NSW, Professor A . Malik Sydney, NSW Center for Lung and Vascular Biology, Department of Dr L . Ittner Pharmacology, University of Illinois, Chicago, IL, US Alzheimer’s & Parkinson’s Disease Laboratory, The Professor S . Mallal Brain and Mind Research Institute, The University of Institute for Immunology and Infectious Diseases, Sydney, Sydney, NSW Murdoch University, Perth, WA Associate Professor R . Khanna Professor P . Martin Tumour Immunology Laboratory, Australian Centre National Vision Research Institute, Carlton, VIC for Vaccine Development, Queensland Institute of Professor J . Mattick Medical Research, Herston, QLD Genomics and Computational Biology, Institute for Professor G . King Molecular Bioscience, University of Queensland, Chemistry and Structural Biology, Institute for Brisbane, QLD Molecular Bioscience, The University of Queensland, Dr G . McConnell Brisbane, QLD Centre for Biophotonics, University of Strathclyde, Dr B . Kile Glasgow, UK Molecular Medicine Division, Walter and Eliza Hall Associate Professor D .L . Minor Institute of Medical Research, Melbourne, VIC Departments of Biochemistry and Biophysics, and Professor M . Larkum Cellular and Molecular Pharmacology, University of Department of Physiology, University of Bern, California, San Francisco, CA, US Bern, Switzerland Dr S . Nutt Dr R .N . Leão Immunology Division, Walter and Eliza Hall Institute Department of Neuroscience, Karolinska Institute, of Medical Research, Melbourne, VIC Stockholm, Sweden Professor M . Nuriya Dr C .H . Lineweaver Department of Pharmacology, School of Medicine, Planetary Science Institute, Research School of Keio University, Tokyo, Japan Astronomy and Astrophysics, Mt Stromlo Observatory, Dr R . Palermo Canberra, ACT Department of Psychology, ANU, Canberra, ACT
The John Curtin School of Medical Research Annual Review 2009 67 Professor W G. . Richards
Dr S . Petrou Dr A . Scalzo Ion Channels and Human Disease Group, Howard Viral Immunogenetics, Lions Eye Institute and Centre Florey Institute, Melbourne, VIC for Ophthalmology and Visual Science, University of Associate Professor A . Purcell Western Australia, Perth, WA Biochemistry and Molecular Biology, The University of Professor K . Shortman Melbourne, Melbourne, VIC Immunology Division, Walter and Eliza Hall Institute Dr A . Ralph of Medical Research, Melbourne, VIC National Center for Epidemiology and Population Dr U . Siebeck Health, ANU, Canberra, ACT Centre for Marine Studies, School of Biomedical Professor W G. . Richards Sciences, University of Queensland, Brisbane, QLD Centre for Computational Drug Discovery, Department Dr B . Slobedman of Chemistry, Oxford University, Oxford, UK Cytomegalovirus Research Group, Westmead Dr M . Robinson Millennium Institute for Medical Research, Westmead, NSW Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, and Epigenetics Dr S . Solomon Laboratory, Garvan Institute, Sydney, NSW Physiology, School of Medical Sciences and Bosch Professor P . Sah Institute, University of Sydney, Sydney, NSW Synaptic Plasticity Laboratory, Queensland Brain Professor A . Strasser Institute, University of Queensland, Brisbane, QLD Molecular Genetics of Cancer Division, Walter and Dr I . Sakala Eliza Hall Institute of Medical Research, Melbourne, VIC Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, Ms R .A . Sweet St Louis, MO, US Department of Immunobiology, Yale University, New Haven, CT, US Professor S-S . Tan Brain Development Group, Howard Florey Institute, University of Melbourne, VIC Professor J . Trapani Cancer Cell Death Laboratory, Peter MacCallum Cancer Research Centre, Melbourne, VIC Dr B . van Leeuwen Research School of Biology, ANU, Canberra, ACT Dr J . van Kleef Visual Sciences, Research School of Biology, ANU, Canberra, ACT Associate Professor B . van Swinderen Cognitive and Behavioural Neuroscience, Queensland Brain Institute, Brisbane, QLD Professor Joe Trapani
68 The John Curtin School of Medical Research Annual Review 2009 Visitors 2009
Dr J . Villadangos Associate Professor G . Wallis Immunology Division, The Walter and Eliza Hall School of Human Movement Studies, University of Institute . Melbourne, VIC Queensland, Brisbane, QLD Professor A . Vingrys Dr P . Waters Optometry and Vision Sciences, University of Comparative Genomics Group, Research School of Melbourne, Melbourne, VIC Biology, ANU, Canberra, ACT Dr P . Visscher Professor J . Whisstock Genetic Epidemiology, Molecular Epidemiology Department of Biochemistry and Molecular Biology, and Queensland Statistical Genetics Laboratories, Monash University, Melbourne, VIC Queensland Institute of Medical Research, Dr D . Yu Brisbane, QLD Garvan Institute of Medical Research, Sydney, NSW Dr I . Vlodavsky Janet and David Polak Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine Research Institute and Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
Professor Ken Shortman Dr Barry Slobedman
The John Curtin School of Medical Research Annual Review 2009 69 Research collaborations 2009
Mr . J .A . Altin, Dr . E .M . Bertram, Dr E . Bertram Professor C .C . Goodnow and Dr . M .C . Cook Role of LIGHT and 4-1BB in immunity to influenza Reduced Treg frequency establishes a Th2 bias Dr S. Turner Department of Microbiology and Dr. A Liston and Ms L. Tian Department of Immunology, The University of Melbourne, Experimental Medicine, University of Leuven, Melbourne, VIC Leuven, Belgium Australian Centre for Vertebrate Mutation Detection Mr . J .A . Altin, Ms . H .J . Rickards, Professor D. Hilton Molecular Medicine Division, Dr . K . Horikawa, Dr . M .C . Cook and The Walter and Eliza Hall Institute of Medical Professor C .C . Goodnow Research, Melbourne, VIC Role of ndfip1 in lymphocytes Professor S.S. Tan Brain Development Group, Dr E . Bertram and Professor C .C . Goodnow Howard Florey Institute, Melbourne, VIC China-Australia Centre for Phenomics Research Professor H. Tang Centre for Infection and Dr N .A . Beard Immunity, Chinese Academy of Sciences, and Properties of calsequestrin and fast and slow Institute of Biophysics, Chinese Academy of twitch skeletal muscle Sciences, Beijing, China Dr R. Murphy and Professor G.D. Lamb Department of Zoology, La Trobe University, Dr A .C . Blackburn Melbourne, VIC Mouse mammary tumour susceptibility loci Professor D.J. Jerry Veterinary and Animal Sciences, Regulation of calcium release channels (RyR2) in University of Massachusetts, Amherst, MA, US cardiac disease Dr D. Laver Hunter Medical Research Institute, Human breast cancer modifier gene discovery University of Newcastle, Newcastle, NSW through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Antibody screening in thyroid eye disease Cancer (kConFab) autoimmunity Dr A. Spurdle The Molecular Cancer Epidemiology Dr V. Calder UCL Institute of Ophthalmology, Laboratory, Queensland Institute of Medical London, UK Research, Brisbane, QLD Actions of triadin on excitation-contraction Dr G. Chenevix-Trench Cancer Genetics coupling Laboratory, Queensland Institute of Medical Professor R.T. Dirksen Department of Research, Brisbane, QLD Pharmacology and Physiology, University of Rochester Medical Centre, Rochester, NY, US Professor P .G . Board Determination of glutathione transferase structures Changes in calsequestrin, triadin and junctin in Professor M. Parker St Vincent’s Medical Research heart failure Institute, Melbourne, VIC Professor S. Gyorke Department of Physiology and Cell Biology, Davis Heart and Lung Institute, The Function of Zeta and Omega class GSTs Ohio State University, Columbus, OH, US Professor M.W. Anders Department of Pharmacology and Physiology, University of Associate Professor J .M . Bekkers Rochester Medical Centre, Rochester, NY, US Excitability and hyperexcitability of neural circuits Structure of γ-glutamyl cyclotransferase in the rodent piriform cortex Dr A. Oakley CSIRO Molecular and Health Professor S. Nelson Brandeis University, Waltham, Technologies, Parkville, VIC MA, US Professor G. Augustine National University of Microbial Omega-like GSTs Singapore, Singapore, and Duke University, Durham, Professor L. Xun School of Molecular Biosciences, NC, US Washington State University, Pullman, WA, US
70 The John Curtin School of Medical Research Annual Review 2009 Research collaborations 2009
Dr M .G . Casarotto Professor A .F . Dulhunty Molecular recognition of the ryanodine receptor Various aspects of ryanodine receptor physiology Dr M. Samso Brigham and Womens Hospital, Dr D. Laver Hunter Medical Research Institute, Harvard Medical School, Boston, MA, US University of Newcastle, Newcastle, NSW Assistant Professor N. Lorenzon Department Contribution of splicing defects in ryanodine of Biological Sciences University of Denver, receptors to myotonic dystrophy Denver, CO, US Professor R.T. Dirksen and Dr L. Wei Department Professor M. Parker Biota Structural Biology of Pharmacology and Physiology, University of Laboratory, St . Vincent’s Institute, Melbourne, VIC Rochester Medical Centre, Rochester, NY, US Structural studies into the mechanism of Actions of triadin on excitation-contraction dihydrofolate reductase coupling Professor G. Roberts Centre for Mechanisms of Professor R.T. Dirksen and Dr L. Wei Department Human Toxicity, University of Leicester, Leicester, UK of Pharmacology and Physiology, University of Dr J. Basran Department of Biochemistry, Rochester Medical Centre, Rochester, NY, US University of Leicester, Leicester, UK Regulatory and pore forming domains of calcium Effects of drugs that block Vpu ion channels release channels and CPVT mutations in the studied with NMR techniques cardiac RyR Professor T. Watts and Dr W. Fischer Professor M. Varsanyi Institut für Physiologische Biomembrane Structure Unit, University of Oxford, Chemie, Ruhr Universität, Bochum, Germany Oxford, UK Structure of ion channel domain peptides Dr J . Chen Professor N. Ikemoto Boston Biomedical Research Roles of IL-3 and its receptor system in acute Institute, Boston, MA, US myeloid leukemia Changes in calsequestrin, triadin and junctin in Dr Y. Wu and Professor Y. Chen Fujian Institute of heart failure Hematology, Fujian Medical University, Fujian, China Professor S. Gyorke Department of Physiology and Effect of microstructured topography on the Cell Biology, Davis Heart and Lung Institute, The calcium homeostasis in liver cells. Ohio State University, Columbus, OH, US Professor Z. Wu College of Bioengineering, FRET analysis of DHPR beta subunit binding to the Chongqing University, China skeletal RyR Dr M . Cook Professor B. Fruen Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Mechanisms of human primary antibody deficiency Minneapolis, MN, US Dr D. Fulcher Westmead Hospital, Westmead, NSW Accessory protein binding sites on the 3D profile of Dr M . Cook, Professor C C. . Goodnow and RyR1 and RyR2 Dr E . Bertram Professor T. Wagenknecht and Dr Z. Liu Mechanisms of hyper-IgE syndromes Wadsworth Center, New York State Department of Dr S. Tangye Garvan Institute of Medical Research, Health, Albany, NY, US Sydney, NSW The 3D location of the SPRY2 domain in RyR1 Dr M. Samso Brigham and Womens Hospital, Dr S . Daley Harvard Medical School, Boston, MA, US Destabilisation of the translocase of the outer mitochondrial membrane by a novel ENU-induced Single channel activity of RyRs from normal human variant of Tomm40 and DM1 muscle. Dr M. Ryan Department of Biochemistry, La Trobe Professor K. North and Dr N. Clarke Discipline of University, Melbourne, VIC Paediatrics and Child Health, The Children’s Hospital at Westmead, The University of Sydney, Sydney, NSW Calsequestrin in the skeletal and cardiac muscle Professor G.D. Lamb Department of Zoology, La Trobe University, Melbourne, VIC
The John Curtin School of Medical Research Annual Review 2009 71 Professor S . Easteal The role of heparanase in rheumatoid arthritis Genome biology of physical performance Dr R. Li and Dr P. Smith The Canberra Hospital, Dr C. Gore and Dr A. Hahn Australian Institute of Canberra, ACT Sport, Canberra, ACT Use of novel HS-mimetics to mobilise haemopoietic Professor J.A. Hawley Exercise Metabolism progenitor and stem cells into the circulation Research Group, School of Medical Sciences, RMIT Dr L. Simson Cancer Immunotherapy Group, Faculty University, Melbourne, VIC of Science, University of Canberra, Canberra, ACT Dr M. Ashenden SIAB Research Pty Ltd, Surfers Design of novel HS-mimetics to inhibit RSV infection Paradise QLD Dr L. Simson Cancer Immunotherapy Group, Cognitive diversity and workplace discrimination Faculty of Science, University of Canberra, Professor P. Easteal Faculty of Law, University of Canberra, ACT Canberra, Canberra, ACT Professor C .C . Goodnow Evolution of functional variation in the Mechanisms regulating islet beta cells in diabetes human genome Dr C. Nolan The Canberra Hospital, Canberra, ACT Dr L. Jermiin Entomology, CSIRO, Canberra, ACT Dr D. MacArthur Wellcome Trust Sanger Institute, Effects of Foxp3 deficiency on islet-specific tolerance Hinxton Hall, UK Professor A. Rudensky and Dr A. Liston Department of Immunology, University of Analysis of risk factors for depression, anxiety, substance use and cognitive change Washington, Seattle, WA, US Professor A. McKinnon and Professor A. Jorm Professor C .C . Goodnow and Dr E . Bertram ORYGEN Youth Health and University of Melbourne, Mutations affecting male fertility Melbourne, VIC Dr M. O’Bryan and Professor D. DeKretser Professor P. Sachdev, Dr W. Wen and Dr K. Monash Institute of Reproduction and Research, Mather School of Psychiatry, The University of New Melbourne, VIC South Wales, Sydney, NSW Mutations affecting the mammary gland Dr A . Enders Dr C. Ormandy Garvan Institute of Medical Molecular function of T-bet Research, Sydney, NSW Dr A. Weinmann Molecular and Cellular Biology Program, University of Washington, Seattle, WA, US Professor C .C . Goodnow and Dr M . Cook Mucin gene functions Development and function of NKT cells Dr M. McGuckin Mater Medical Research Institute, Professor D. Godfrey Department of Immunology, Brisbane, QLD University of Melbourne, Melbourne, VIC Transport of Phospholipids and B cell development Professor C .C . Goodnow, Dr E . Bertram, Dr in mice. C .G . Vinuesa and Dr L . Tze Professor B. Beutler and Dr O. Siggs, Department Identifying genes for immunity and tolerance of Genetics, The Scripps Research Institute, La Jolla, Dr J. Cyster, Professor L. Lanier and Professor A. CA, US Weiss University of California, San Francisco, CA, US Transport of Phospholipids and B cell development in humans. Professor C .C . Goodnow, Dr E . Bertram and Dr K. Schwarz, Department of Molecular Ms B . Whittle Diagnostik, Institute for Clinical Transfusion Hearing mutations Medicine, and Immunogenetics, Ulm, Germany Dr H. Dahl Murdoch Children’s Research Institute, Melbourne, VIC Dr C . Freeman Use of HS-mimetics to prevent Alzheimer’s disease Professor C .C . Goodnow and Dr A . Enders Professor D. Small and Dr M. Beckman NKT cell mutations Department of Biochemistry and Molecular Biology, Professor D. Godfrey Department of Immunology, Monash University, Melbourne, VIC The University of Melbourne, Melbourne, VIC
72 The John Curtin School of Medical Research Annual Review 2009 Research collaborations 2009
Professor C .C . Goodnow and Dr G .F . Hoyne Professor J .E . Gready and Ms T . Vassilieva Role of cbl genes in B and T-cell tolerance Regulation of prion protein and doppel by FAC1 Associate Professor W. Langdon and Dr C. Thien Assistant Professor K. Jordan-Sciutto School School of Pathology and Laboratory Medicine, of Dental Medicine, University of Pennsylvania, University of Western Australia, Perth, WA Philadelphia, PA, US Professor C C. . Goodnow and Dr C G. . Vinuesa Professor C .E . Hill Immunity and Infection Genomics Consortium Localisation of voltage dependent calcium Dr R. Cornall Nuffield Department of Clinical channels in cerebral and mesenteric arteries using Medicine, Oxford University, Oxford, UK immunoelectron microscopy Professor J. Bell The Weatherall Institute of Dr S.L. Sandow Department of Pharmacology, Molecular Medicine, Oxford University, Oxford, UK School of Medical Sciences, The University of New South Wales, Sydney, NSW Molecular and cellular studies of the adaptive immune response in health and disease Identification of IP3 receptor subtypes in arteries Professor C. Mackay, Professor J. Sprent, Dr R.J.H. Wojcikiewicz Department of Professor F. Mackay, Emeritus Professor A. Pharmacology, SUNY Upstate Medical University, Basten, Dr S. Tangye and Dr R. Brink Garvan Syracuse, NY, US Institute of Medical Research, Sydney, NSW Endothelium-derived vasodilators Professor B. Fazekas Centenary Institute of Cancer Dr J.R. Falck Southwestern Medical Center, Medicine and Cell Biology, The University of Sydney, University of Texas, Dallas, TX, US Sydney, NSW Role of T-type calcium channels in control of Professor J E. . Gready cerebrovascular tone Identification of CTLDs in prasinophytes Dr L.C. Cribbs Cardiovascular Institute, Loyola Professor A. Worden Monterey Bay Aquarium University Medical Center, Loyola, IL, US Research Institute, Moss Landing, CA, US Use of function blocking antibodies to investigate Dr A. Zelensky Department of Genetics, Erasmus the role of TRP channels in vasomotor function Medical Center, Rotterdam, The Netherlands Professor D.J. Beech Institute of Membrane and Professor J E. . Gready and Mr M .J . Abraham Systems Biology, University of Leeds, Leeds, UK MD challenge simulations on the BlueGene Professor T . Hirst Dr T. Dale and Mr C. McMurtrie BlueFern Antibody and peptide ligands as probes of protein Supercomputing Centre, University of Canterbury, folding Christchurch, NZ Dr R. James Department of Infection, Immunity and Inflammation, University of Leicester, Professor J E. . Gready and Mr A . Agrawal Leicester, UK Identifying wheat germplasm in international Dr M. Sack Department of Molecular gene banks with superior Rubiscos for breeding for Biotechnology, RWTH Aachen University, increased drought tolerance Aachen, Germany Dr K. Street ICARDA (International Center for Agricultural Research in the Dry Areas), Aleppo, Syria E coli heat-labile enterotoxin adjuvant, Dr A.G. Condon CSIRO Plant Industry, Canberra, ACT EtxB, antigen trafficking, and MHC class I antigen presentation Professor J E. . Gready, Dr P .L . Cummins and Professor A. Morgan Department of Cellular and Dr I .V . Rostov Molecular Medicine, University of Bristol, Bristol, UK Application of the ONIOM QM/MM method to Biotech commercialisation opportunities simulation of enzyme reactions Dr E. Giri-Rachman Arifin SITH, Institute for Dr T. Vrevren and Dr M.J. Frisch GAUSSIAN Inc, Techology, Bandung, Indonesia New Haven, CT, US
The John Curtin School of Medical Research Annual Review 2009 73 Dr G .F . Hoyne Estimation of molecular coevolution Delta3-Notch signalling in T-cell development and Dr G. Caporaso Department of Chemistry and function and Role of Ikaros in the control of Notch Biochemistry, University of Colorado, Boulder, CO, US signalling in T cell development Development of a software library for Associate Professor S. Dunwoodie and Dr G. genomic biology Chapman Developmental Biology Program, The Dr R. Knight Department of Chemistry and Victor Chang Cardiac Research Institute, Sydney, NSW Biochemistry, University of Colorado, Boulder, CO, US Dr G .F . Hoyne and Professor C .C . Goodnow Development of Markov-process models to measure Studies on beta cell islet homeostasis and the influence of sequence-neighbourhoods on metabolic perturbations in ENU variant mice mutation dynamics Dr G. Farrell and Dr C. Nolan Department of Dr V.B. Yap Department of Statistics and Applied Endocrinology, The Canberra Hospital, Canberra, ACT Probability, National University of Singapore, Singapore Dr G .F . Hoyne, Professor C .C . Goodnow and Dr T . Juelich Dr E . Bertram Elucidation of transcriptional mechanisms for Role of hnRNPLL in generating protective immunity the establishment and maintenance of CD8 T-cell to mycobacteria tuberculosis effector gene function in a mouse influenza A model Dr B. Saunders and Professor W. Britton Dr S. Turner Department of Microbiology and Mycobacterial Research Group, Centenary Institute Immunology, The University of Melbourne, of Cancer Medicine and Cell Biology, Sydney, NSW Melbourne, VIC Dr G .F . Hoyne and Professor M .F . Shannon Chromatin structure and transcriptional gene Role of c-rel in regulatory T-cell differentiation and silencing of HIV-1 homeostasis Associate Professor A. Kelleher National Centre in Dr S. Gerondakis The Immunology Division, The HIV Epidemiology and Clinical Research, University Walter and Eliza Hall Institute of Medical Research, of New South Wales, Sydney, NSW Melbourne, VIC Chromatin structure and transcriptional regulation Dr G .A . Huttley in human regulatory T-cells Dr N. Sedikki National Centre in HIV Epidemiology Dissecting the genotype-phenotype relationship for and Clinical Research, University of New South (alpha)-actinin-3 in humans Wales, Sydney, NSW Professor K. North Discipline of Paediatrics and Child Health, The Children’s Hospital at Westmead, Gene copy number variation in differentiated cells The University of Sydney, Sydney, NSW – a CGH Analysis Dr D. MacArthur Wellcome Trust Sanger Institute, Dr R. McInnes Agilent Technologies, Melbourne, VIC Hinxton Hall, UK Associate Professor G . Karupiah and APOSLE study - Identification of susceptibility Dr G . Chaudhri alleles in Australian SLE patients Pathophysiological significance of reverse Dr M. Cook The Canberra Hospital, Canberra, ACT signalling through membrane TNF Statistical machine learning approaches to Dr J. Sedgwick Bone and Inflammation Research, predicting nucleosome placement Lilly Research Laboratories, Eli Lilly and Company, Professor A. Smola National ICT Australia (NICTA), Indianapolis, IN, US Canberra, ACT Dr B. Saunders Mycobacterial Research Group, The Tammar wallaby genome project. Centenary Institute of Cancer Medicine and Cell Dr M. Wakefield Bioinformatics Division, The Biology, Sydney, NSW Walter and Eliza Hall Institute of Medical Research, Modulation of the immune response by poxvirus Melbourne, VIC encoded immune evasion molecules Signal processing techniques suitable for analyses Professor R.M.L. Buller Department of Molecular of epigenetic and DNA sequence data. Microbiology and Immunology, St Louis University, Dr J. Epps School of Electrical Engineering and St Louis, MO, US Telecommunications, The University of New South Wales, Sydney, NSW
74 The John Curtin School of Medical Research Annual Review 2009 Research collaborations 2009
Genetic control of early immune responses Recovery of human cone photoreceptors to poxviruses following bleaching Dr A. Scalzo The Lions Eye Institue, Perth, WA Dr O.A.R. Mahroo Department of Physiology Dr W. Yokoyama Washington University School of Development and Neuroscience, University of Medicine, St Louis, MO, US Cambridge, Cambridge, UK Investigating the role of dendritic cell subsets in Professor J . Licinio anti-poxviral immune response Translational studies in obesity Dr G. Belz Immunology Division, The Walter and Professor S. Bornstein and Dr M. Ehrhart- Eliza Hall Institute of Medical Research, Bornstein University of Dresden, Germany Melbourne, VIC Dr S. Mueller, Department of Microbiology and Imaging of leptin-deficient subjects Immunology, University of Melbourne, Professor E.D. London Departments of Psychiatry and Melbourne, VIC Biobehavioral Sciences, and Molecular and Medical Pharmacology, David Geffen School of Medicine, Tracking virus-specific B cells using Blimp-1 University of California, Los Angeles, CA, US transgenic mice Dr S. Nutt Immunology Division, The Walter and Genetics studies in ethnic minorities Eliza Hall Institute of Medical Research, Professor M.A. Oquendo Department of Psychiatry, Melbourne, VIC Columbia University Medical Center, Columbia University, New York, NY, US Investigating virus-specific memory B cells and long-lived antibody secreting cells Professor J . Licinio and Dr R. Brink Autoimmunity Research Unit, Garvan Professor M-L . Wong Institute of Medical Research, Sydney, NSW Dr T. Newsome School of Molecular and Microbial Imaging of leptin-deficient subjects Biosciences, University of Sydney, Sydney, NSW Professor C. Shannon-Weickert The Schizophrenia Research Laboratory, Neuroscience Research Dr M . Kole Australia and The University of New South Wales, Interferon- modulation of dendritic and axonal Sydney, NSW HCN channels Dr. T Weickert The Cognitive Neuronal Systems Dr U. Strauss Institute for Cell and Neurobiology, Unit, The Schizophrenia Research Laboratory, Charité - Medical University of Berlin, Berlin, Germany Neuroscience Research Australia and The University of New South Wales, Sydney, NSW Kinetics of Kv1 channels in layer 5 pyramidal neuron axons Neuroendocrine outcomes of inflammation and stress Dr S. Hallermann Carl-Ludwig-Institute of Professor V. Rettori Center of Pharmacological and Physiology, Medical Faculty, University of Botanical Studies, CEFYBO-CONICET-UBA, School of Leipzig, Leipzig, Germany Medicine, University of Buenos Aires, Argentina Professor T D. . Lamb Genetics of depression Dr C. Dong Department of Psychiatry and Behavioral Molecular basis for functional differences between Sciences, University of Miami, Miami, FL, US rod and cone photoreceptors Professor E.N. Pugh Jr Department of Dr M . Lobigs Ophthalmology, University of Pennsylvania, Flavivirus virulence and vaccination Philadelphia, PA, US Dr R.A. Hall Department of Microbiology and Evolution of the vertebrate eye Parasitology, The University of Queensland, Professor S.P. Collin School of Biomedical Sciences, Brisbane, QLD The University of Queensland, Brisbane, QLD Viral factors involved in flavivirus replication and Involvement of GRKs in shut-off of the rod’s virus/host interactions response to light Dr A. Khromykh School of Molecular and Microbial Dr Y. Fukada Department of Biophysics and Sciences, The University of Queensland, Brisbane, QLD Biochemistry, Graduate School of Science, Tokyo Flavivirus morphogenesis University, Tokyo, Japan Professor M.L. Ng Department of Microbiology, Dr S. Kawamura Graduate School of Frontier National University of Singapore, Singapore Bioscience, Osaka University, Osaka, Japan
The John Curtin School of Medical Research Annual Review 2009 75 Dengue virus replication Gliotoxin as virulence factor in Aspergillosis Dr A. Davidson Department of Cellular and Professor M. Simon Max Planck Institute für Molecular Medicine, University of Bristol, Bristol, UK Immunbiologie, Freiburg, Germany Dr M . Lobigs and Dr P D. . Cooper Gliotoxin mediated apoptosis Dr J. Pardo Foundation Aragon, University of Flavivirus vaccines based on inulin adjuvants Zaragoza, Zaragoza, Spain Professor N. Petrovsky Department of Diabetes and Endocrinology, Flinders Medical Centre, Adelaide, SA Professor A . Müllbacher, Dr M . Lobigs and Dr T. Komiya and Dr H. Torinawa Research Center Dr M . Regner for Biologicals, The Kitasato Institute, Saitama, Japan Pathobiology and immune evasion of Ectromelia virus Professor K .I . Matthaei Dr J. Pardo Foundation Aragon, University of Zaragoza, Zaragoza, Spain New ADAR 1 mouse model for interferon action in Dr E. Galvez University of Zaragoza, Zaragoza, Spain human viral diseases Dr M. Frese School of Health Sciences, University Professor A . Müllbacher and Dr M . Regner of Canberra, Canberra, ACT The granzymes in early defence against viral infection New Mx1 Mouse Model for Interferon Action in Dr J. Trapani and Dr V. Sutton Peter MacCallum Influenza Virus infection Cancer Centre, Melbourne, VIC School of Health Sciences, University Dr M. Frese Role of granzymes in cytolytic leukocyte-mediated of Canberra, Canberra, ACT killing and viral-induced immunopathology The role of the S100 multigene family in inflammation Professor M. Simon Max Planck Institute für Professor C. Geczy Inflammatory Diseases Research Immunbiologie, Freiburg-Zahringen, Germany Unit, School of Medical Sciences, The University of Dr R. Wallich Department of Immunology, New South Wales, Sydney, NSW University of Heidelberg, Heidelberg, Germany The role of IL-5 and eosinophils in gut allergy The role of poxvirus encoded serpins in cytotoxic Assistant Professor S. Hogan Division of Allergy T-cell induced apoptosis and Immunology, Cincinnati Children’s Hospital Dr J. Pardo Foundation Aragon, University of Medical Center, Cincinnati, OH, US Zaragoza, Zaragoza, Spain The role of IL-5 and eosinophils in allergy Gamma irradiated influenza virus as a vaccine Professor M. Rothenberg Division of Pulmonary against bird flu Medicine, Allergy and Immunology, Cincinnati Dr D. Boyle and Dr T. Bowden CSIRO Livestock Children’s Hospital Medical Centre, Cincinnati, OH, US Industries, Australian Animal Health Laboratory, Geelong, VIC Parasite infection in gene deficient mice Dr M. Alsharifi Infectious Diseases Laboratories, Dr L. Dent Eosinophil Biology Laboratory, Institute of Medical and Veterinary Science, Microbiology and Immunology, School of Molecular Adelaide, SA and Biomedical Science, Adelaide University, Adelaide, SA Dr P . Papathanasiou Professor K .I . Matthaei, Dr M . Kole and Dr ENU Mutagenesis for the Identification of Genes Regulating Hematopoietic Stem Cells C . Raymond Dr A. Perkins Institute for Molecular Bioscience, Function and mechanisms of ADAR-mediated Brisbane, QLD editing in the brain Dr J. Pimanda Faculty of Medicine, University of Dr M. Frese School of Health Sciences, University New South Wales, Sydney, NSW of Canberra, Canberra, ACT Professor C .R . Parish Professor A . Müllbacher Role of platelets in tumour metastasis Oral induced T-cell tolerance Professor B. Chong School of Pathology, The Dr J. Chin Elizabeth MacArthur AG Institute, NSW University of New South Wales, Sydney, NSW Department of Agriculture, Camden, NSW Professor R. Stocker Department of Pathology, University of Sydney, Sydney, NSW
76 The John Curtin School of Medical Research Annual Review 2009 Research collaborations 2009
Mechanisms of immune thrombocytopenia Development of live attenuated SIV/HIV vaccines Professor B. Chong School of Pathology, The Dr J. Mak HIV Assembly Group, Centre for Virology, University of New South Wales, Sydney, NSW Burnet Institute for Medical Research, Melbourne Vic Development of dendritic cell targeting vaccines Dr C . Ranasinghe Associate Professor D. Jackson Department of HIV pox-virus vaccines and evaluation of Microbiology and Immunology, The University of CD8 T-cell avidity Melbourne, Melbourne, VIC Dr J. Stambas Department of Microbiology Development of a liposome-based TB vaccine and Immunology, The University of Melbourne, Professor W. Britton Mycobacterial Research Melbourne, VIC Group, Centenary Institute of Cancer Medicine and Mucosal HIV vaccines and TB vaccines Cell Biology, Sydney, NSW Professor A. Ramsay Gene Therapy Program, Heparan sulfate and Alzheimer’s disease Louisiana Vaccine Centre, Louisiana State University Professor D. Small Menzies Research Institute, Health Sciences Centre, New Orleans, LA, US University of Tasmania, Hobart, TAS TNF family members and immune responses to Novel angiogenesis inhibitors viral infection Dr P. Karuso Department of Chemistry and Dr L. Sedger Institute for the Biotechnology of Biomolecular Sciences, Macquarie University, NSW Infectious Diseases, The University of Technology, Islet heparan sulphate and Type I Diabetes Sydney, NSW Professor R. Rodgers Department of Obstetrics and Type I and II interferon studies Gynaecology, University of Adelaide, Adelaide, SA Dr M. Frese Faculty of Applied Science, University of Canberra, Canberra, ACT Professor I .A . Ramshaw Evaluation of HIV prophylactic and Dr D . Rangasamy therapeutic vaccines LINE-L1 Retrotransposition events in human Dr S. Kent Department of Microbiology and cancer lines Immunology, The University of Melbourne, Professor G. Schumann Paul-Ehrlich-Institute, Melbourne, VIC Langen, Germany Design of HIV-1 vaccines Epigenetic regulation during brain development in Dr D. Boyle CSIRO Livestock Industries, Australian offspring of diabetic pregnancy Animal Health Laboratory, Geelong, VIC Associate Professor S. Thameem Dheen National University of Singapore, Singapore Development of vaccines against genetically modified viruses Activation of L1 Retrotransposon is associated with Professor A. Ramsay Gene Therapy Program, breast cancer development Louisiana Vaccine Centre, Louisiana State University Professor J. Dahlstrom The Canberra Hospital, Health Sciences Centre, New Orleans, LA, US Canberra, ACT Development of a novel TB vaccine Bioinformatic analysis of the mouse L1 elements Professor W. Britton Mycobacterial Research Dr. S-Y.Cho Hanyang University, Seoul, South Korea Group, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW Dr S . Rao Microarray functional analysis Evaluation of a nasopharyngeal cancer Associate Professor G. Denyer School of Molecular therapeutic vaccine and Microbial Biosciences, The University of Sydney, Professor D. Moss Division of Immunology, Sydney, NSW Queensland Institute of Medical Research, Brisbane, QLD HIV and RNAi strategies Associate Professor A. Kelleher National Centre in Development of enhanced immune responses to HIV Epidemiology and Clinical Research, University HIV vaccines of New South Wales, Sydney, NSW Professor P. Doherty and Dr S. Turner Department of Microbiology and Immunology, The University of Regulatory T-cells and transcriptional regulation Melbourne, Melbourne, VIC Dr N. Seddiki HIV Immunovirology Research Laboratory, Centre for Immunology, Sydney, NSW
The John Curtin School of Medical Research Annual Review 2009 77 Effector function gene analysis Micro RNAs and control of transcription in Laureate Professor P. Doherty and Associate cancer metastasis Professor S. Turner Department of Microbiology Dr G. Goodall Cytokine Research Laboratory, and Immunology, The University of Melbourne, Hanson Institute, Adelaide, SA Melbourne, VIC High throughput sequencing of epigenetic marks Analysis of ChIP-on-Chip data Dr E. Dennis CSIRO Plant Industry, Canberra, ACT Dr T. Taya and Dr R. McInnes Agilent Technologies, Tokyo, Japan and Melbourne, VIC Dr C .J . Simeonovic Heparan sulfate and heparanase expression in Dr C .R . Raymond human pancreas LTP in the hippocampus of mGlu5 knockout mice Clinical Associate Professor J.D. Wilson Professor A. Lawrence Addiction Neuroscience Department of Endocrinology, The Canberra Laboratory, Howard Florey Institute, Melbourne, VIC Hospital, Canberra, ACT Contribution of astrocytic signalling to Dr C .J . Simeonovic and synaptic metaplasticity Professor C .R . Parish Professor W.C. Abraham Brain Health and Repair Research Centre, Department of Psychology, Heparanase expression in atheroslerotic plaques University of Otago, Dunedin, NZ Dr C. Hagemeyer Atherosclerosis and Vascular Biology Laboratory, Baker Heart and Diabetes Editing of serotonin receptors by interferon Institute, Melbourne, VIC Dr M. Frese Faculty of Applied Science, University of Canberra, Canberra, ACT Dr C .J . Simeonovic, Professor C .R . Parish and Ms F .J . Choong Dr M . Regner Remodelling of the islet BM after islet isolation Granzymes in lymphocyte migration and transplantation Associate Professor P. Bird Monash University, Professor R. Rodgers and Dr H. Irving-Rodgers Melbourne, VIC Department of Obstetrics and Gynaecology, The Pathology of degranulation deficiencies in University of Adelaide, Adelaide, SA cytotoxic T cells Professor C. Geisler and Dr M. von Bohde Dr C .J . Simeonovic and Dr A F. . Ziolkowski University of Copenhagen, Copenhagen, Denmark Local blockade of co-stimulation pathways in cellular xenotransplantation Virulence factors in mousepox Professor M. Sandrin Department of Surgery, Professor R. M. Buller, Department of Austin Health and University of Melbourne, Microbiology and Immunology, University of St Melbourne, VIC Louis, St Louis, MO, US Mathematical models of in vivo Dr C .J . Simeonovic, Dr A .F . Ziolkowski and T and NK cell cytotoxicity Professor C .R . Parish Dr V. Ganusov Los Alamos National Laboratory, Los Mechanisms of beta cell destruction in Suppressor Alamos, NM, US Of Cytokine Signalling 1 (SOCS1) overexpressing Non Obese Diabetic mice. Professor M F. . Shannon Dr H. Thomas and Dr K. Graham Immunology and Control of GM-CSF gene transcription in T-cells Diabetes Unit, St Vincent’s Institute, Melbourne, VIC Dr A. Holloway Discipline of Biochemistry, University of Tasmania, Hobart, TAS Dr Z-M . Song The role of c-Rel in CD28 signaling and regulatory Investigation of the non gut phenotype in networks in T-cells Hirschsprung’s disease (HSCR): Changes in the Dr S. Gerondakis Immunology Division, The adrenal glands of a rat model of HSCR Walter and Eliza Hall Institute of Medical Research, Associate Professor D. Croaker Gastrointestinal Melbourne, VIC Unit, The Canberra Hospital, Canberra, ACT The role of Foxp3 in regulatory T-cells Dr S. Barry Department of Paediatrics, The University of Adelaide, Adelaide, SA
78 The John Curtin School of Medical Research Annual Review 2009 Research collaborations 2009
Associate Professor C . Stricker Imprinted X inactivation in mammals Parameter optimisation of sequences of EPSCs Dr J. Lee Massachusetts General Hospital, Boston, Professor J.H. Manton Department of Electrical and MA, US Electronic Engineering, The University of Melbourne, Chromatin remodelling during X inactivation Melbourne, VIC Dr E. Heard Curie Institute, Paris, France Short-term dynamics provide temporal filtering at Dr S. Dimtrov Institut Albert Bonniot, synapses in neocortex Grenoble, France Dr B.P. Graham Department of Computing Science Dr A. Peters Friedrich Miescher Institute for and Mathematics, University of Stirling, Stirling, UK Biomedical Research, Basel, Switzerland Chromatin remodelling during oogenesis Professor G J. . Stuart Dr J. Bowles Institute for Molecular Bioscience, Interaction of action potentials with inhibitory University of Queensland, Brisbane, QLD synaptic events Professor M. Häusser The Wolfson Institute for Dr L . Tze Biomedical Research, University College, London, UK CD83 regulation of MHC II and CD86 expression on Role of HCN channels in absence epilepsy MCMV-infected cells. Dr S. Petrou Howard Florey Institute, The University Professor M. Degli-Esposti and Associate of Melbourne, Melbourne, VIC Professor C. Andoniou Lions Eye Institute, Perth, WA Professor S. Berkovic Department of Medicine, Dr C .G . Vinuesa Austin Health, The University of Melbourne, Melbourne, VIC Molecular and cellular studies of T:B interactions Associate Professor T. O’Brien Department of Dr R. Brink Immunology Program, Garvan Institute Medicine, The University of Melbourne, Melbourne, VIC of Medical Research, Sydney, NSW Tfh cell development and biology Dr M L. . Tierney Professor C. Mackay Center for Immunology and Gating of coupled GABAA channels Inflammation, Department of Immunology, Monash Dr D. Laver Hunter Medical Research Institute, University, Melbourne, VIC University of Newcastle, Newcastle, NSW Roquin, Tfh cells and miRNAs GABAA receptor expression and function in testis Professor P. Leedman, Dr A. Barker and and sperm Dr K. Giles, Laboratory for Cancer Medicine, Professor H. Chan Chinese University of Hong Kong, Western Australian Institute for Medical Research, Hong Kong, China University of Western Australia, Perth, WA Dr Q-J. Li Department of Immunology, Duke Effect of trafficking on the channel properties of 5HT3 receptors University Medical Center, Durham, NC, US Dr S.C. Lummis Cambridge University, Cambridge, UK Investigating of the convergence of Roquin and Foxo1 pathways in the regulation of T cell homeostasis Protein interactions in glycine receptors - effects on ion permeation properties Professor R. Flavell Yale University School of Professor P. Barry, Dr T. Lewis and Dr J. Carland Medicine, New Haven, CT, US University of New South Wales, Sydney, NSW Professor M. Li Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, US Professor D .J . Tremethick Investigating the kinetics of Roquin / RNA interactions The role of histone variants in modulating Professor N. Dixon School of Chemistry, University chromatin fibre dynamics of Wollongong, Wollongong, NSW Dr K. Luger Department of Biochemistry and Regulation of short-lived effector CD8+ cell Molecular Biology, Colorado State University, Fort survival by Roquin Collins, CO, US Professor W.R. Heath The Department of The structure and function of histone variants Microbiology and Immunology, The University of during spermatogenesis Melbourne, Parkville, VIC Dr C. Caron Institut Albert Bonniot, Grenoble, France
The John Curtin School of Medical Research Annual Review 2009 79 Dr C .G . Vinuesa and Dr M . Cook Professor J .A . Whitworth and Dr Y . Zhang APOSLE study - Identification of susceptibility Effects of antioxidants and glucocorticoids on alleles in Australian SLE patients plasma F2-isoprostane concentrations Dr S. Addlestein Royal Prince Alfred Hospital, Associate Professor K. Croft and Dr T. Mori Sydney, NSW School of Medicine and Pharmacology, Royal Perth Dr S. Riminton Repatriation General Hospital, Hospital Unit, The University of Western Australia, Sydney, NSW Perth, WA Dr D. Fulcher Westmead Hospital, Sydney, NSW Glucocorticoid receptors in knockout mice Dr S. Alexander Children’s Hospital, Sydney, NSW Dr T.J. Cole Department of Biochemistry and Dr P. Pavli The Canberra Hospital, Canberra, ACT Molecular Biology, Faculty of Medicine, Nursing and Professor B . Walmsley Health Sciences, Monash University, Melbourne, Vic Mechanisms of central neuronal integration Hypertension in rats Professor R.E.W. Fyffe Center for Brain Research, Dr R. Lin The School of Biotechnology and Wright State University, Dayton, OH, US Biomolecular Sciences, The University of New South Wales, Sydney, NSW Activity dependent changes in brainstem auditory pathways Effect of glucocorticoid and sepiapterin on plasma Dr R. Leao Karolinska Institutet, Stockholm, Sweden total biopterin concentrations Dr K. Leao Department of Neuroscience, Dr J. Earl Children’s Hospital at Westmead, Developmental Genetics, University of Uppsala, Westmead, NSW Uppsala, Sweden Dr R . Williams Associate Professor H .S . Warren Trans regulatory architecture of the human genome Lymphocyte populations in diffuse large B-cell (and Dr X. Xie University of California, Irvine, CA, US other aggressive) Non-Hodgkin’s lymphoma Integrative genomics of PI3K in a murine model of Dr D. Talaulikar Department of Haematology, The cardiomyopathy Canberra Hospital, Canberra, ACT Dr J.R. McMullen Cardiac Hypertrophy Laboratory, Dr D .C . Webb Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC The development of allergic inflammation in the Dr R.C.Y Lin School of Biotechnology and lungs of GSTP-/- mice Biomolecular Sciences, University of New South Professor R. Wolf and Dr C. Henderson Ninewells Wales, Sydney, NSW Hospital and Medical School, Dundee, UK The role of Ym1/2 in regulating allergic inflammation Dr R . Williams, Professor S . Easteal and Associate Professor R. Kumar Department of Dr J . Henderson Pathology, The University of New South Wales, Studies on expression biomarkers for obesity and Sydney, NSW metabolic syndrome Professor P.S. Foster Discipline of Immunology Professor J.A. Hawley Exercise Metabolism and Microbiology, The University of Newcastle, Research Group, School of Medical Sciences, RMIT Newcastle, NSW University, Melbourne, VIC Ciliated cell specific expression of GSTP-/- Expression biomarkers for detection of Dr L. Ostrowski University of North Carolina, blood doping Chapel Hill, NC, US Dr M. Ashenden SIAB Research Pty Ltd, Surfers Expression of Ym1/2 proteins in a mouse Paradise, QLD arthritis model Professor C. Gore Australian Institute of Sport, Dr R. Wilson Skeletal Biology, Murdoch Children’s Canberra, ACT Research Institute, Parkville, VIC Professor M-L . Wong Professor J .A . Whitworth Pharmacogenomics of depression Mechanism(s) by which glucocorticoids induce Dr M. Arcos-Burgos National Human Genome hypertension in humans Research Institute, National Institutes of Health, Dr J. Kelly and Dr G. Mangos St George Hospital, Bethesda, MD, US Sydney, NSW
80 The John Curtin School of Medical Research Annual Review 2009 Research collaborations 2009
Pharmacogenetics of antidepressants Cytokine receptors Professor A. Llerena Department of Pharmacology Dr J. Murphy Molecular Medicine Division, The and Psychiatry, Faculty of Medicine, University of Walter and Eliza Hall Institute of Medical Research, Extremadura, Badajoz, Spain Melbourne, VIC Professor I .G . Young Role of IL-3 in allergic inflammation Professor P.S. Foster School of Biomedical Role of IL-3 receptor in myeloid leukaemia Sciences and Pharmacy, University of Newcastle, Professor Y. Chen Fujian Medical University, Newcastle, NSW Fuzhou, China
The Australian Phenomics Facility
Professor R. Flower National Blood Authority, Dr D. Nikolic-Paterson Department of Nephrology, Canberra, ACT Monash Medical Centre, Monash University, Clayton, VIC Dr B. Saunders and Professor W. Britton Mycobacterial Research Group, Centenary Institute Associate Professor M. O’Bryan Department of of Cancer Medicine and Cell Biology, Sydney, NSW Anatomy and Developmental Biology, Monash University, Clayton, VIC Dr G. Smythe School of Community Health, Charles Sturt University, Albury, NSW Dr I. Smyth Developmental Biology of the Skin, Department of Anatomy and Developmental Dr C. Ormandy Cancer Research Program, Garvan Biology, Monash University, Clayton, VIC Institute of Medical Research, Sydney, NSW Dr M. Wallace Department of Physiology, Monash Dr L. Wu Genentech Inc ., San Francisco, CA, US University, Clayton, VIC Dr C. Wells National Adult Stem Cell Research Dr P. Farlie Craniofacial Research, Murdoch Centre, Eskitis Institute for Cell and Molecular Children’s Research Institute, Parkville, VIC Therapies, Griffith University, Nathan, QLD Associate Professor H. Dahl and Dr S. Manji Professor A. Rudensky Memorial Sloan-Kettering Genetic Hearing Research, Murdoch Children’s Cancer Center, New York, NY, US Research Institute, Parkville, VIC Dr D.G. Gilliland Merck Research Laboratories Dr R. Cornall Nuffield Department of Clinical (MRL), Merck & Co ., Inc ., Whitehouse Station, NJ, US Medicine, Oxford University, Oxford, UK Professor J. Bertram and Dr G. Caruana Renal Associate Professor V. Harley and Dr S. Bagheri- Development and Regeneration Research Group, Fam Sex Determination & Gonadal Development, Department of Anatomy and Developmental Prince Henry’s Institute, Clayton, VIC Biology, Monash University, Clayton, VIC Professor R. d’Andrea Leukemia Biology, The Dr H. Abud Epithelial Regeneration Laboratory, Women’s & Children’s Health Research Institute, Department of Anatomy and Developmental Adelaide, SA Biology, Monash University, Clayton, VIC Dr M. Frese School of Health Sciences, University Dr A. Hart Molecular Embryology Laboratory, of Canberra, Canberra, ACT Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC Associate Professor A. Liston VIB Autoimmune Genetics Laboratory, Department of Experimental Associate Professor T.J. Cole Department of Medicine, K .U .Leuven, Leuven, The Netherlands Biochemistry and Molecular Biology, Faculty of Medicine, Nursing and Health Sciences, Monash cont. University, Melbourne, VIC
The John Curtin School of Medical Research Annual Review 2009 81 The Australian Phenomics Facility cont . Research collaborations 2009
Associate Professor I. van Driel Department Associate Professor R. Wallace Discipline of of Biochemistry and Molecular Biology, Faculty Medicine, The University of Queensland, Brisbane, QLD of Medicine, Dentistry and Health Science, The Associate Professor C. Wicking Division of University of Melbourne, Parkville, VIC Molecular Genetics and Development, Institute for Dr J. White Faculty of Veterinary Science, The Molecular Bioscience, The University of Queensland, University of Melbourne, Parkville, VIC St Lucia, QLD Dr J. Pimanda Faculty of Medicine, University of Professor J. Götz and Dr L. Ittner Alzheimer’s and New South Wales, Sydney, NSW Parkinson’s Disease Laboratory, The Brain and Mind Research Institute, University of Sydney, Associate Professor R. Ashman School of Dentistry, Sydney, NSW The University of Queensland, Brisbane, QLD Professor M.D. Grounds School of Anatomy and Professor T. Gonda Molecular Oncogenesis Human Biology, University of Western Australia, Group, The UQ Diamantina Institute for Cancer, Perth, WA Immunology and Metabolic Medicine, The University of Queensland, Brisbane, QLD Associate Professor J. Xu Centre for Orthopaedic Research, School of Surgery, University of Western Professor P. Koopman Division of Molecular Australia, Perth, WA Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Professor R. Harvey Developmental Biology St Lucia, QLD Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW Associate Professor A. Perkins Division of Molecular Genetics and Development, Institute for Professor A. Strasser and Dr D. Gray Molecular Molecular Bioscience, The University of Queensland, Genetics of Cancer Division, Walter and Eliza Hall St Lucia, QLD Institute of Medical Research, Melbourne, VIC
82 The John Curtin School of Medical Research Annual Review 2009 Staff & Students
The following section provides a directory of staff and students of JCSMR during 2009 by Program.
The John Curtin School of Medical Research Annual Review 2009 Emerging Pathogens & Vaccines Program Staff 2009
Head of Program Research Fellow and Team Leader Lobigs M., BSc (Hons), PhD Ranasinghe C., BSc (Rouen), MPhil (Colombo), PhD (UWA) Visiting Fellows Program Administrator Enemark C., BA, LLB, PhD Mitigas R. Jackson R.J., BSc(Hons) (Monash), PhD (Edin) Cellular Microbiology Group Ramsay A.J., BSc, PhD (Otago) Professor and Leader Laboratory Manager Hirst T., BSc(Hons) (Kent), DPhil (York) Medveczky C.J., AssocDipTechBiol (TAFE) (part-time) Postdoctoral Fellow Technical Officers Johnson-Saliba M., BSc(Hons), MSc (Cape Town), PhD Tu W.J., BSc (Hubei Uni Technology China), MBioTech (Hons) Pavlinovic L., DipAppSci Molecular Virology Group Visiting Technical Officer Fellow and Leader Buchanan A., BHealthSci (UC) Lobigs M., BSc (Hons), PhD Research Fellow Viral Immunology Group Bettadapura J., MSc, PhD (Bangalore) (until July) Professor and Leader Müllbacher A., BSc, MSc (Auck), PhD Visiting Fellows Cooper P.D., DSc, PhD (Lond) Research Fellow Lee E., BSc(Hons), PhD Regner M., Diplom-Chemiker (Kaiserslautern), PhD Senior Technical Officers Visiting Fellows Lobigs P., AssocDipMedSci Alsharifi M., BBioMedSci(Hons) (Monash), PhD Pavy M., AssocDipAppSc (CIT), BAppSci (UC) Blanden R.V., MDS (Adel), PhD, FAA Chin J., MSc(Hons) (UQ), PhD (UQ) Vaccine Immunology Group Senior Technical Officer Professor and Group Leader Koskinen A., AssocDipMedSci Ramshaw I.A., MSc (Brunel), PhD
84 The John Curtin School of Medical Research Annual Review 2009 Genome Biology Program Staff 2009
Professor and Head of Program Gene Expression and Epigenomics Group Tremethick D.J., BSc(Hons) (USyd), PhD (MacqU) Professor and Leader Shannon M.F., BSc(Hons), PhD (National University Program Administrator of Ireland) Mitigas R. Postdoctoral Fellows Chromatin and Transcriptional Hardy K., BSc(Hons) (USyd), PhD (USyd), Masters(EScience) Regulation Group Greaves I., PhD Professor and Leader Fan J., BSc (Fudan), MSc (Fudan), PhD (Auckland) Morris M., PhD (from March) Tremethick D.J., BSc(Hons) (USyd), PhD (MacqU) Postdoctoral Fellows Technical Officers Ma L., MAppSci (Horticulture) (NZ) Soboleva T., MSc (MSU), PhD Pagler E., BSc (Santo Tomas) (from May) Nekrasov M., PhD (Heidelberg) Savkina M., PhD (New Jersey) Molecular Systems Biology Group Amrichova J., PhD (Brno) Fellow and Leader Technical Officers Williams R., BAppSc, PhD (UNSW) Langton L.K., BSc, AssDipAppSci (Path) (CIT) Senior Scientific Programmer Shen, Q. Lawrence C., BSc(Hons) (UNSW), MA (Delaware), Computational Genomics Group GradDipCompSci (UNSW) (part-time) Fellow and Leader Predictive Medicine Group Huttley G.A., BSc(Hons) (MacqU), PhD (UC Riverside) Professor and Leader Research Assistant Easteal S., BSc(Hons) (St Andrews), MBA, PhD (Griffith) Pahwa A., BSc (UNSW) Postdoctoral Fellows Computational Proteomics and Therapy Das D., BSc(Hons) (Presidency College, Kolkata), MSc Design Group (Madurai Kamaraj), PhD (Nehru Centre, Bangalore) (from July) Professor and Leader Henderson J., BSc (Ottawa), MSc (Calgary), PhD (USyd) Gready J.E., BSc(Hons), PhD (USyd), FRACI (from February) Research Officer Visiting Fellows Cummins P.L., BSc(Hons), PhD (USyd) Cherbuin N., DipNursing (Lausanne), BA (UNSW), Postdoctoral Fellow BSc(Hons), PhD Kannappan B., BSc (Madras), MSc, PhD (Pune) Gore C., Dip Teaching (SACAE), BEd (SACAE), BEd(Hons) Research Assistants (Flinders), PhD (Flinders) Ward J., BSc(Hons) (UNSW) (part-time) (August - Scott B., BSc(Hons) (UQ), PhD November) Senior Technical Officer Vassilieva T., MSc (Novosibirsk) (part-time) (from Tan X., BSc (Shandong), MSc (China Pharmaceutical) November) Visiting Scholar Visiting Fellows Mather K., BSc(Hons) (La Trobe), BSc(Hons), Armarego W.L.F., PhD, DSc (ULond), FRSC, FRACI GradDipPsy (CSU) Rostov I.V., BSc (Kazan), PhD (Karpov Institute) Visiting Fellows Epigenetics and Genome Stability Group Barlin G., PhD, DSc (USyd), FRANC Leader Cox G., BSc, PhD (UMelb), FAA Denborough M., MD, ChB (Cape Town), MD (UMelb), DPhil Rangasamy D., MSc, MTech (India), PhD (UK) (Oxon), DSc (UMelb), FRCP Morrison J.E., BSc (USyd), MSc (UQ), DPhil (Oxon), DSc
The John Curtin School of Medical Research Annual Review 2009 85 Immunology Program Staff 2009
Professor and Head of Program Visiting Researcher Goodnow, C.C., BVSc(Hons)(USyd), BScVet (Hons)(USyd), Cabalda-Crane V.M., BSc (U Santo Tomas, Manila), PhD PhD (USyd), FAA, FRS (Birmingham) (September – December) Senior Technical Officer Program Administrator Bezos A., BSc (USyd), MSc (USyd) (part-time) Weil E.T.F. Technical Officers Assistant Program Administrator Browne A., BA (part-time) Peace C. (until August) (part-time) Glidden M. Asthma and Allergy Group Laboratory Technician Fellow and Leader Davis S.D.A., BSc(Hons) (Adel) (from June) Webb D.C., DipMedLabSc (RMIT), BAppSc (UC), PhD (UC) Visiting Technical Officer Postdoctoral Fellow Lo P-H., BSc (National Cheng Kung University, Taiwan), Zhou J., BMed (Guangxi Med), MMed (Guangxi Med), PhD MBioTech, MPhil Senior Technical Officer Editorial/Administrative Assistant Cai Y., BMed (Beijing Med) Parish B., BSc (Madras), BSc, MSc, GradDipCompStudies (UC) (part-time) Cancer and Human Immunology Laboratory Associate Professor and Laboratory Leader Diabetes/Transplantation Immunobiology Warren H.S., BSc(Hons), PhD (UQ) Laboratory Fellow and Laboratory Leader Research Assistant Simeonovic C.J., BSc(Hons), PhD Gonzalez Y., BSc (UJaveriana, Colombia), MSc (Wollongong) (on secondment from ANUMS) Postdoctoral Fellows Wu Z., MSc (UNSW), BM (ZhongShan), PhD Cancer and Vascular Biology Group Ziolkowski A., BMedSc(Hons), PhD Professor and Leader Visiting Fellows Parish C.R., BAgrSc (UMelb), PhD (UMelb) McCullagh P., MBBS (UMelb), DPhil (Oxon), MRCP (Lond), Fellow MD (UMelb) Freeman C., BSc(Hons) (Adel), PhD (Adel) Wilson J.D., BSc(Hons), MBBCh, BAO(Hons), MD (Queens, Research Fellows Belfast), MRCP (UK), FRACP Hindmarsh E.J., BSc(Hons) (USyd), PhD Technical Officers Rao S., BSc(Hons) (Keele), PhD (Kings College Lond) Brown D., AssDipAppPath (CIT) (casual) NHMRC Peter Doherty Postdoctoral Fellow Hamilton P., Certificate II (Animal Tech) (CIT) (part-time) Quah B., BSc, PhD Popp S.K., BSc, AssDipAppSci (Biol) (CIT) (part-time) Widesiundara D.K., BBioTech(Hons) (from April) Postdoctoral Fellows Juelich T., BSc(Hons) (Stuttgaart), PhD Immunogenomics Group Sutcliffe E., BSc(Hons), PhD (from September) Professor and Laboratory Head Visiting Fellows Goodnow C.C., BVSc(Hons) (USyd), BScVet(Hons) (USyd), Ada G.L., DSc (USyd), FAA PhD (USyd), FAA, FRS Chesterman C, MBBS (USyd), DPhil (Oxon), FRACP, FRCPA Laboratory Manager (until July) Townsend M., PathTech Cert (TAFE), AssDipAppPath Chong G, MBBS (Hons), BMedSc (Monash) FRACS, FRCS (Bruce TAFE) (C) FRCS (E), Diplomate, American Board of Surgery (US) Li R., MD (China Medical University), PhD (Southern Cross) Immune Tolerance and Signalling Laboratory Parish M., BSc(Hons), PhD (Cambridge) (from December) Professor and Leader Price J., BSc(Hons) (UMelb), PhD (UMelb) Goodnow C.C., BVSc(Hons) (USyd), BScVet(Hons) (USyd), Staykova M., PhD (USofia) PhD (USyd), FAA, FRS Vlodavsky I., BSc, MSc (Technion, Haifa), PhD (Hebrew University) (August-October)
86 The John Curtin School of Medical Research Annual Review 2009 Immunology Program – staff 2009
Senior Research Fellow CJ Martin Fellow Hoyne G. F., BSc(Hons) (UWA), PhD (UWA) Ellyard J., BAs, BSc(Hons), PhD (until September) Postdoctoral Fellow Research Fellow Rigby R., BSc (Sheffield Hallam), Bertram E., BSc(Hons) (Adel), PhD (Adel) PhD (Imperial College Lond) CJ Martin Fellow Visiting Fellows Papathanasiou P., BSc(Hons), LLB(Hons), PhD Silva D., MBBS (Colombia), PhD Postdoctoral Fellows Cook M., MBBS (USyd), FRACP, FRCPA, PhD (USyd) Yu D., BSc (Wuhan), PhD Daley S., BVSc (UQ), DPhil (Oxon) Horikawa K., MD (Chiba), PhD (Tokyo) Laboratory Technical Staff Tan A., BSc(Hons), MSc, PhD (NUS) (from July) Hogan J., BMedSci (UC), GradDipGenCouns (Newcastle) NHMRC Peter Doherty Postdoctoral Fellow Hu X., BSc (Beijing Institute of Technology) Srivastava M., MSc (Rewa) (part-time) Tze L., BSc (Beloit), PhD (Minnesota) Visiting Fellows Research Assistants Athanasopoulos V., PhD (UMelb) (until August) Athanasopoulos V., PhD (UMelb) (from September) Cornall R., PhD Wilson A., BSc(Hons) (UC), RN (part-time) (until September) Fahrer A., BSc(Hons) (UMelb), PhD (UMelb) Infection and Immunity Group Hoyne G.F., BSc(Hons) (UWA), PhD (UWA) (from September) Associate Professor and Leader Laboratory Technical Staff Karupiah G., BSc(Hons), MSc (Malaya), PhD In charge of pre-immune serology Research Fellow Domaschenz H., PathTechCert (TAFE) Chaudhri G., BSc(Hons), PhD Research Technicians Postdoctoral Fellows Howard D., BSc Panchanathan V., MBBS, MPhil (Malaya), PhD Roots C., BAppSci (UC) Sakala I., BMedSci (Zambia), PhD (until February) Balakishnan B., BSc(Hons) (from February) Visiting Fellows Laboratory Assistants Belz G., BVBiol (UQ), BVSc(Hons) (UQ), PhD (UQ) Hoyne R. (casual) (until September) Newsome T.P., BSc(Hons) (UMelb), PhD (Inst Molecular Yabas E. BSc, MSc (casual) (from September) Pathology, Vienna) (from August) Animal Experimental Project Co-ordinator Ng E., BMedSc(Hons), PhD (from July) Way D., BSc, BSc(Hons) (JCU) Scalzo A., BSc (Hons) (UMelb), PhD (UMelb) Dip GradDipSecondarySciEd (UC) Tscharke D.C., BSc(Hons) (Adel), PhD (Adel) Saunders B.M., BSc(Hons) (UMelb), PhD (UMelb) Ramaciotti Immunization Technical Officers Genomics Laboratory Eldi P., MBBS (India), MSc (UQ) Research Fellow Jian P., BMed (Medical University NingXia) (until August) Enders A., MD, PhD (Freiburg) Sendall E., BMedSci(Hons) (casual) (from November) Laboratory Technical Staff Tan A., BBioTech(Hons) Ter L.K., BBioTech(Hons) (casual) (from November) In charge of immune serology Tha Hla R., BRTC (TAFE) (July-August) Kucharska E., BSc, MSc (Warsaw) Wei B., BMed (Beijing Medical University) Occupational Trainee Frankenreiter S. (from September) Translation Research Unit (joint with The Canberra Hospital) (from October) Humoral Immunity and Senior Fellow and Leader Autoimmunity Group Cook M., MBBS (USyd), FRACP, FRCPA, PhD (USyd) Viertel Senior Medical Research Fellow and Leader Research Assistant Vinuesa C.G., LMS(MBBS) (Madrid), DRCOG (Lond), MSc, Wilson A., BSc(Hons) (UC), RN (part-time) PhD (Birmingham)
The John Curtin School of Medical Research Annual Review 2009 87 Neuroscience Program Staff 2009
Professor and Head of Program Movement & Memory Laboratory Stuart G.J., BSc(Hons) (Monash), PhD Leader Raymond C.R., BSc(Hons) (Otago), PhD (Otago) Program Administrator Khalidi D. (from February) Postdoctoral Fellow Lohmann P, DiplBiol (Ulm), PhD (Berlin) Senior Technical Officer Rodda G.R., PTC Visiting Fellow Hulme S., PhD (Otago) (October-November) Blood Vessel Group Synapse & Hearing Group Professor and Leader Hill C.E., BSc(Hons), PhD, DSc (UMelb) Synapse and Hearing Laboratory Postdoctoral Fellows Professor and Leader Ellis A., BSc (Monash), BApplSc (RMIT), PhD (RMIT) Walmsley B., BE, PhD (Monash), DSc (UNSW) Seymour V., BSc(Hons) (Otago), PhD (until July) Postdoctoral Fellow Wolfle SE, BPharm (Heidelberg), Dr rer nat (Lubeck) Garrett A., BSc(Hons) (UWA), PhD (UWA) Haddock R.E., BSc (Wollongong), BSc(Hons), PhD (from July) Neuronal Network Laboratory Everitt A., BSc, PhD (from July) Associate Professor and Leader Research Officers Stricker C., MD (Zurich), PhD (Bern) Chaston D.J., BSc(Hons) Research Fellow Baillie B., BSc(Hons) (JCU), PhD (JCU) Cowan A.I., BSc(Hons), PhD Cerebral Cortex Group Visual Neuroscience Group Associate Professor and Leader Professor and Leader Bekkers J.M., BSc(Hons) (Griffith), MSc (Manchester), Lamb T.D., BE (UMelb), ScD (Cambridge), FRS, FAA PhD (Cambridge) Postdoctoral Fellow Postdoctoral Fellows Vogalis F., PhD (Monash) Suzuki N., BSc (Tsukuba), MMedSci (Tsukuba), PhD (Tokyo) Visiting Fellow Ikeda K., BA (UColorado, Boulder), PhD (until September) Reinholz F., PhD (URostock) Neuronal Signalling Group Visiting Fellows Neuronal Signalling Laboratory Hirst G.D.S., BSc, PhD (Leeds), FAA Professor and Leader Edwards F.R., BE, PhD (Monash) Stuart G.J., BSc (Hons) (Monash), PhD University Fellow and Emeritus Professor Postdoctoral Fellows Curtis D.R., AC, MBBS (UMelb), PhD, FRACP, FAA, FRS Breton, J-D., MSc, PhD (Strasbourg) Cavazzini M., BSc (Hons) (Sydney), MSc (Oxford), PhD (Oxford) (from March) Kole M.H.P., MSc, PhD (Groningen) (until May) Ikeda K., BA (UC Boulder), PhD (from October) Visiting Fellows Herrera, M., BSc (Sonora), MSc (Querétaro) (September - December) Brain Development Laboratory Leader Song Z-M., MMSc (Jiamusi), PhD (Flinders)
88 The John Curtin School of Medical Research Annual Review 2009 Structural Biology Program Staff 2009
Professor and Head of Program Molecular Genetics Group Board P.G., BSc(Hons), PhD (UNE) Professor and Leader Board P.G., BSc(Hons), PhD (UNE) Program Administrator Research Fellow Khalidi, D. (from February) Blackburn A., BSc(Hons) (UNSW), PhD Biomolecular Structure Group Postdoctoral Fellows Fellow and Leader Liu D., PhD (USyd) Casarotto M.G., BSc(Hons) (UMelb), PhD (UMelb) Zhou H., MSc (ShenYang Agricultural), PhD (Institute of Botany, Chinese Academy of Sciences) (until November) Postdoctoral Fellows Theodoratos A., BSc(Hons) (USyd), PhD Cui Y., MA (Central China), PhD (Chinese Academy of Science) Visiting Fellows Norris N., PhD (York) (from October) Baker R., BSc(Hons)(UNSW), PhD Dahlstrom J., MBBS(Hons), FPAC, PhD, FRCPA, GradCertEdSt Technical Officers Shield A., BBiotech(Hons) (Flinders), PhD (Flinders) Hekimian L., DipLabTech (CIT) (until August) Senior Technical Officer Cytokine Molecular Biology and Coggan M., BSc(Hons) (until November) Signalling Group Laboratory Technicians Professor and Leader Cappello J., BSc (UC), AD AppSciAnSci (CIT) Young I.G., MSc (UMelb), PhD Rooke M., BMedSci (Pharm Sci) (CSU) Peile M., DipAnTech (CIT) Postdoctoral Fellow Chen J., BSc (China), MMed (China), PhD (Flinders) Muscle Research Group Visiting Fellow Professor and Leader Murphy J., BSc, PhD Dulhunty A.F., BSc (USyd), PhD, DSc (UNSW) Visiting Scholars Senior Research Adviser Guohua X., BSc (China), MSc (China) (from October) Gallant E., PhD (Minnesota) Zhipeng K., MD (China), PhD (China) (from April) Research Fellow Technical Officers Beard N.A., BAppSci(Hons) (LaTrobe), PhD Olsen J., BSc Senior Technical Officer Ewens C. Pace S., BSc (UTS) Membrane Physiology and Ion Channel Laboratory Technicians Signaling Group Stivala J. Research Fellow and Leader Jacunza M. Tierney M.L., BSc, MSc (Otago), PhD Stem Cell and Gene Targeting Group Visiting Fellow Professor and Leader Everitt A., PhD Matthaei K.I., BSc(Hons) (UNSW), PhD Research Assistant Visiting Fellows Curmi J., BOptom(Hons) Abdullah J.A. bin M., PhD Hopkinson K., DipAppSc (UC), BSc App (UC), Dip APMA (Monash) Frese M., BSc (Osnabrück), PhD (Freiburg) Megirian D., PhD (Rochester) Laboratory Technicians Taylor H.I. Ward J., BSc(Hons) (until March)
The John Curtin School of Medical Research Annual Review 2009 89 Translational Medicine Program (from September) Staff 2009
Professor and Head of Program Research Fellows Licinio J., MD (Universidade Federal da Bahia, Brazil), FAPA Paz-Filho G., MD (Universidade Federal do Paraná, Brazil) Mastronardi C.A., PhD (Buenos Aires, Argentina) Program Administrator Technical Officer Vitler L. Weaver L., DipLabTech (CIT) Translational Medicine Group Pharmacogenomics Group Professor and Group Leader Professor and Group Leader Licinio J., MD (Universidade Federal da Bahia, Wong M-L., MD (São Paulo, Brazil) Brazil), FAPA
Australian Phenomics Facility Staff 2009
Director Phenome Bank Coordinator Winslade S.L., BA(Hons) (UNE), PhD (UNE) Read S.H., BSc(Hons)(Adel), PhD(Adel) Cryopreservation and IVF Coordinator Head of Scientific Programs Butterworth C. Bertram E., BSc(Hons) (Adel), PhD (Adel) Senior Project Technicians Deputy Director Adams V. McKenzie A., BSc(Hons) Kofler J., BSc, Dip Ani Tech (CIT) (from October) Australian Phenomics Network Liaison Officer Tunningley R., BMedSci Macintosh R.J., BBiotech Technical Officer Scientific Programs Manager Wilson H., BSc (until August) Sjollema G.E., BSc(Hons) Saxena K., BScBiotech, MTechMan (UNSW) (from August) Scientific Projects Manager APN Bioinformatics Specialist Subramaniam A.S., BBiotech(Hons) Xu K., BEng (Shanghai Jiao Tong University, China), PhD (UQ) (from October) Scientific Business Manager Dobbie M.S., BAppSc (UTS), MSc (USyd), PhD (Lond) Scientific Project Coordinators Armstrong J., BSc(Hons) (Otago) (until July) Craven A., BAnimalSci (JCU) (from June) Balakishnan B., BSc(Hons) High Blood Pressure Research Unit Staff 2009
Professor and Head Senior Technical Officer Whitworth J.A., AC, FTSE, DSc, MD, PhD, BS (UMelb), MD Langton L.K., BSc, AssDipAppSci (Path) (CIT) (until January) (Honoris causa) (USyd), MD (Honoris causa) (UNSW), DSc Technical Officers (Honoris causa) (Glasgow), FRACP, FAICD (until July) Vickers J.J., BMedSc (UC), RN, RM, GradCert (UC) Research Fellow (until January) Zhang Y., BMed (Beijing), PhD (Adel) Sutton M. (until May) Clinical Research Assistant Visiting Fellows Williamson P.M., SRN (seconded to St George Hospital, Kelly J.J., MBBS(Hons), MD (UNSW) (until July) Sydney, NSW) (until July) Mangos G.J., MBBS, MD (UNSW), FRACP (until July)
90 The John Curtin School of Medical Research Annual Review 2009 91 Students 2009
PhD Scholars 2009 Linterman M., BBMEDS (Victoria, Wellington) Abraham M.J., BSc (UTas), MPhil Luo J., BE (Bioinformatics)(Hons), MPhil Addis S., BMedSci(Hons) (Malaya) Mapp S., MBBS (UMelb), FRACP, FRCPA Agrawal A., BSc, MSc (JNKVV, Jabalpur) Dipl McCuaig R., BSc (UC), GradDipSciMolBiol, BSc(Hons) (UTas) Bioinformatics (BAB, Bangalore) McNaughton E., BSc(Hons) (Otago) Altin J., PhB(Hons), LLB (Hons) Md Nor N., MSc (Nottingham) Alshekaili J., BSc, MD (from November) Mirza S., BSc(Hons) (Dhaka), MSc (BioTech) (UNSW) Bell S., Bsc(Hons) (from August) Mohan A., BTech Brew J.M., BMedSci(Hons) Morris M., BBiomedSci(Hons) (JCU) Chan S-Y., BBiotech(Hons) Ng E., BMedSci(Hons) Chang P.P., BSc (Malaya), MSc (Malaya) (from December) Ong S., MBBS (UNSW), BSc (UNSW), FRACP Chen G. Poon I., BBiomedSci(Hons) (Monash) Chen L. Cho E., BSc (Auck), GradDipSci (Auck) Ramiscal R., BSc(Hons) Choong F-J., BMedSci(Hons) Randall K., MBBS(UNSW), BSc(UNSW), FRACP, FRCPA Choy J., BSc(Hons) Rosenberg M., BSc(Hons) (Canterbury) Chua A., BSc Rudinski S., BSc(Hons) Corley S.M., LLB (UQ), LLM (USyd), BSc(Hons) (USyd) Sammut R., BAppSc (Monash), BEc(Hons) (Monash) Coupland L., BSc(Hons), RN Silva C., BSc, MSc Er C.C., BBiotech(Hons) Simpson N., MBBS (USyd), MPH (UNSW) Feng J. Smith C.L.C., BSc(Hons) French H.E., BSc(Hons) (Otago) Sontani Y., BSc (Murdoch), BSc(Hons) French H., BSc (UNSW) Srivastava M., MSc Furuya Y., BSc(Hons) (Auck) Sun R., BTech(Hons) Han S-Y., BSc(Hons) Sutherland D., BMedSci(Hons) Hanna A., BSc(Hons) (from August) Tae H.S., BSc(Hons) (Malaysia) He Y., MSc (Sun Yat-Sen) Tahiliani V., BSc (SUNY Albany), GradDipBiochem Hewawasam R.P., BSc(Hons) (Peradeniya), MPhil (Ruhuna) Tan E., BMedSci(Hons) Horan C.R., BMedSci(Hons) Tan X., BSc, MSc Hussain M., BSc(Hons) Teh C., PhB(Hons) Johnstone V.P.A., BSc(Hons) Townsend D., BAppSci(Hons) (UC), BForensicSci (UC) Karunasekara Y., MD (USSR) Tuazon J., BSc, MD Ji J., BSc(Hons) (USyd) Kuo I., BSc(BioMed) (UWA), BSc(Hons) Vassilieva T., MSc (Novosibirsk) Larena M., BSc, MD Willemse H., BSc(Hons), MSc Lee S. Wong W.Y., BSc(Hons) (Adel) Lee S-H. Weiss S., BAppSc (Swinburne), PhD (USyd), MFinMgt, Grad Lee S-K., BSc(Hons), MBiotech Cert Commercialisation Leffler M., BMedSc(Hons) (MacqU) Wen B. Li J., BMedSci(Hons) Yee D., BSc(Hons) (Auck) Li L., BSc(Biotech) Ying H., BBiol (Nanjing), MSc(Nanjing) Lim P.S., BBiomedSci(Hons) Xi Y., BEng, MBiotech Lindsay H., BMathSci (Newcastle), BSc(Hons) Zafar A., BVSc, MVSc
91 The John Curtin School of Medical Research Annual Review 2009 91 Students 2009
MPhil Scholars 2009 Vacation Scholars 2009 Campbell Z., BSc(Hons) Buthelezi N. Mercan S. Das S. Ravichandran J., BSc(Hons) Fenix K. Susanti S. Hu D. Yabas M. Hutchinson I. Wu F. Khanna M. Lee Y. Honours Students 2009 Lun A. Beaton L. Martin J. Boland C. To M-S. Fitch J. Trivedi S. Hu D. Webb R. Jelall Y. Yu X-W. Newman S. Zhou Z. Rebbeck R. Sendall E. Visiting Scholar 2009 Ter L-K. Li L. Wium E.
Undergraduate Research Students 2009 Munindradasa A.R. Booth I. David M. Jakhetia R. Ng A. Das S. Saunders J. Amirah N. A. Rajendran E. Pratama A. Vohra M.
92 The John Curtin School of Medical Research Annual Review 2009 93 School Administration & Services
School Administration School Services Director Australian Cancer Research Foundation Shannon M.F., BSc(Hons), PhD (National University of Biomolecular Resource Facility (ACRF-BRF) Ireland) (until September) Licino J., MD (Universidade Federal da Bahia, Brazil) FAPA Manager (from September) Palmer S., BSc(Hons), MBA (Tech Management) (LaTrobe) Deputy Director Technical Specialist Easteal S., BSc (Hons) (St Andrews), MBA, PhD (Griffith) Milburn P., BSc(Hons), PhD (Sheffield) Business Manager Genomics Team Webb B., BRTC (CIT), AdvDipBusMan (CIT) Higgins A., CBLT (USQld) McCrae C., BiolTech Cert (CIT) Emeritus Professor and School Visitor Ohms S., MBChB, ME, PhD (Auckland) Fenner F., AC, CMG, MBE, FRS, FAA, MD, DTM, Hon Md, Dr Peng K., PhD (Wuhan) honoris causa (Liege), FRACP, FRCP (ULond) Zhang K., MSc (Fudan), PhD Executive Assistant to Director Proteomics Team Vitler L. McAndrew K., AssDipAppSci (UC) Administrative Assistant McCrae C., BiolTech Cert (CIT) Morales D. Zhang K., MSc (Fudan), PhD Functions Assistant Administrative Assistant Rathbone G.K. Moore S. Public Affairs and Communications Unit Microscopy and Cytometry Public Affairs Manager Resource Facility (MCRF) Nicol M.J., BSc (Wollongong), BSc(Hons), PhD Head Senior Multimedia Officer Gillespie C.M., GradCertMic (USyd) Edwards K., PhotCert Histology Unit Multimedia Officer Prins A.S., BAppSci (RMIT) Macklin J.A., PhotCert (casual) Flow Cytometry Unit Education Vohra H., MSc(Hons) (Punjab), PhD (PGIMER) Devoy M., BSc(Hons) Associate Director (Education) and Medical Sciences Graduate Convener Cowan, A., BSc(Hons), PhD, GradCertHE Student Administrator Abou-Rida, M. (part-time)
93 The John Curtin School of Medical Research Annual Review 2009 93 School Services – staff 2009
Operations Technical Services Media and Wash-up Section Manager Stewart B., Elec Trades Cert TAFE (North Sydney) Manager (until June) Metcalfe C., DipBus, Cert IV Management, Coombes D. (from June) Cert IV Vet Nursing Technical Officers Supervisor and Technical Officer Best N. Gilmartin L., Cert III Lab skills (CIT) Cremer P. Technicians Gair L. Munday K. Jakubaszek R. Thileebhan S. Jordan T. Keys B. Operations Section Percival M. Operations Manager Rhall G. Metcalfe C., DipBus, Cert IV Management, Robertson A. Cert IV Vet Nursing Trades Assistant Administrative Assistant Jones S. Firth S. (until Oct) Apprentice Operations Assistant Kynoch M. Ciuffetelli L. Trainee Senior Storeperson Champion G. Clements R. Administrative Assistant Storeperson Firth S. (until November) Talbot A. Dowling E. (from November) Baker M. (August-December) Safety & Training Section Adviser McKenzie K., AssDipAppSci (Animal Sci) (CIT), IT Cert III (CIT)
94 The John Curtin School of Medical Research Annual Review 2009 Publications, Patents & Presentations
A list of the publications, including peer reviewed journal articles, invited reviews and book chapters authored by JCSMR staff and students in 2009 appears on the following pages.
Also included is a list of patents registered by JCSMR staff and students during the year.
JCSMR Staff and students have made scientific presentations at conferences nationally and internationally, and at other research institutes during 2009. These presentations are listed here.
The John Curtin School of Medical Research Annual Review 2009 Publications 2009
Alonso, H., Cummins, P.L., and Gready, J.E. (2009) Brähler, S ., Kaistha, A ., Schmidt, V .J ., Wölfle, S.E., Busch, Methyltetrahydrofolate:corrinoid/iron-sulfur Protein C ., Kaistha, B .P ., Kacik, M ., Hasenau, A .L ., Grgic, I ., Methyltransferase (MeTr): Protonation State of the Si, H ., Bond, C .T ., Adelman, J .P ., Wulff, H ., de Wit, C ., Ligand and Active-Site Residues . Journal of Physical Hoyer, J ., and Köhler, R . (2009) Genetic deficit of SK3 Chemistry B 113(44):14787-14796 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and Alsharifi, M., Furuya, Y., Bowden, T .R ., Lobigs, M., causes hypertension . Circulation 119(17):2323-2332 Koskinen, A., Regner, M., Trinidad, L ., Boyle, D .B ., and Müllbacher, A. (2009) Intranasal Flu Vaccine Breton, J.-D. and Stuart, G.J. (2009) Loss of sensory Protective against Seasonal and H5N1 Avian input increases the intrinsic excitability of layer 5 Influenza Infections . PloS One 4(4):e5336 pyramidal neurons in rat barrel cortex . Journal of Physiology-London 587(21):5107-5119 Anel, A ., Bleackley, C ., Borner, C ., Golstein, P ., Krammer, P H. ., Müllbacher, A., Pardo, J ., Simon, M .M . and Cai, Y., Kumar, R .K ., Zhou, J., Foster, P .S ., and Webb, D.C. Trapani, J .A . (2009) EMBO workshop on cytotoxicity, (2009) Ym1/2 promotes Th2 cytokine expression by cell death and the immune system . Cell Death and inhibiting 12/15(S)-lipoxygenase: identification of a Differentiation 16(5):790-793 novel pathway for regulating allergic inflammation . Journal of Immunology 182(9):5393-5399 Armarego, W.L.F. and Chai, C .L .L . (2009) Purification of Laboratory Chemicals . 6th Edn . Elsevier, Oxford Cai, Y.P., Zhou, J.S. and Webb, D.C. (2009) Treatment of mice with fenbendazole attenuates allergic Beard, N.A., Wei, L. and Dulhunty, A.F. (2009) Control airways inflammation and Th2 cytokine production of muscle ryanodine receptor calcium release in a model of asthma . Immunology and Cell Biology channels by proteins in the sarcoplasmic reticulum 87(8):623-629 lumen . Clinical and Experimental Pharmacology and Physiology 36(3):340-345 Chaudhri, G., Quah, B.J., Wang, Y., Tan, A.H.Y., Zhou, J., Karupiah, G. and Parish, C.R. (2009) T Beard, N.A., Wei, L. and Dulhunty, A.F. (2009) Ca2+ cell receptor sharing by cytotoxic T lymphocytes signaling in striated muscle: the elusive roles of triadin, facilitates efficient virus control . Proceedings of the junctin, and calsequestrin . European Biophysics Journal National Academy of Sciences of the United States with Biophysics Letters 39(1):27-36 of America 106(35):14984-14989
Beckman, M ., Freeman, C., Parish, C.R. and Small, Chen, J.Z. and Liu, X.S. (2009) The role of interferon D .H . (2009) Activation of cathepsin D by gamma in regulation of CD4(+) T-cells and its clinical glycosaminoglycans . FEBS Journal 276(24): implications . Cellular Immunology 254(2):85-90 47343-7352 Chen, J.L., Olsen, J., Ford, S., Mirza, S., Walker, A., Bekkers, J.M. (2009) Synaptic Transmission: Excitatory Murphy, J.M. and Young, I.G. (2009) A New Isoform of Autapses Find a Function? Current Biology Interleukin-3 Receptor alpha with Novel Differentiation 19(7):R296-R298 Activity and High Affinity Binding Mode . Journal of Biological Chemistry 284(9):5763-5773 Binder, H ., Brucker, J . and Burden, C.J. (2009) Nonspecific Hybridization Scaling of Microarray Chen, J.Z. and Deng, Y.M . (2009) Influenza virus antigenic Expression Estimates: A Physicochemical Approach variation, host antibody production and new approach for Chip-to-Chip Normalization . Journal of Physical to control epidemics . Virology Journal 6:30-30 Chemistry B 113(4):2874-2895 Cherbuin, N ,. Reglade-Meslin, C ,. Kumar, R ,. Jacomb, P ,. Easteal, S., Christensen, H ,. Sachdev, P . and Anstey, K J. . (2009) Risk Factors of Transition from Normal Cognition to Mild Cognitive Disorder: The PATH through Life Study . Dementia and Geriatric Cognitive Disorders 28(1):47-55
96 The John Curtin School of Medical Research Annual Review 2009 Publications 2009
Chu, J ., Hong, N .A ., Masuda, C .A ., Jenkins, B .V ., Nelms, Ellis, A., Goto, K., Chaston, D.J., Brackenbury, T.D., K A. ., Goodnow, C.C., Glynne, R .J ., Wu, H ., Masliah, E ., Meaney, K.R., Falck, J .R ., Wojcikiewicz, R .J .H ., Joazeiro, C .A ., and Kay, S .A . (2009) A mouse forward and Hill, C.E. (2009) Enalapril Treatment alters genetics screen identifies LISTERIN as an E3 ubiquitin the Contribution of Epoxyeicosatrienoic Acids ligase involved in neurodegeneration . Proceedings but not Gap Junctions to Endothelium-Derived of the National Academy of Sciences of the United Hyperpolarizing Factor Activity in Mesenteric States of America 106(7):2097-2103 Arteries of Spontaneously Hypertensive Rats . Journal of Pharmacology and Experimental Therapeutics Cook, M.C. and Tangye, S .G . (2009) Primary immune 330(2):413-422 deficiencies affecting lymphocyte differentiation: lessons from the spectrum of resulting infections . Ellis, L., Bots, M ., Lindemann, R .K ., Bolden, J .E ., Newbold, International Immunology 21(9):1003-1011 A ., Cluse, L .A ., Scott, C .L ., Strasser, A ., Atadja, P ., Lowe, S .W . and Johnstone, R .W . (2009) The histone Cowley, M J. ., Cotsapas, C .J ., Williams, R.B.H., Chan, deacetylase inhibitors LAQ824 and LBH589 do not E .K F. ., Pulvers, J .N ., Liu, M .Y ., Luo, O.J., Nott, D .J ., and require death receptor signaling or a functional Little, P F. .R . (2009) Intra- and inter-individual genetic apoptosome to mediate tumor cell death or differences in gene expression . Mammalian Genome therapeutic efficacy . Blood 114(2):380-393 20(5):281-295 Enemark, C . and Ramshaw, I.A. (2009) Gene Technology, Cridland, S O. ., Keys, J .P ., Papathanasiou, P. and Perkins, Biological Weapons, and the Security of Science . A C. . (2009) Indian hedgehog supports definitive Security Studies 18(3):624-641 erythropoiesis . Blood Cells, Molecules and Diseases 43(2):149-155 Everitt, A.B., Seymour, V.A.L., Curmi, J., Laver, D .R ., Gage, P.W. and Tierney, M.L. (2009) Protein Cui, Y.F., Tae, H.S., Norris, N.C., Karunasekara, Y., interactions involving the gamma 2 large cytoplasmic Pouliquin, P., Board, P.G., Dulhunty, A.F. and loop of GABA(A) receptors modulate conductance . Casarotto, M.G. (2009) A dihydropyridine receptor FASEB Journal 23(12):4361-4369 alpha(1s) loop region critical for skeletal muscle contraction is intrinsically unstructured and binds Foong, Y.Y., Jans, D.A., Rolph, M .S ., Gahan, M .E . and to a SPRY domain of the type 1 ryanodine receptor . Mahalingam, S. (2009) Interleukin-15 mediates International Journal of Biochemistry and Cell potent antiviral responses via an interferon- Biology 41(3):677-686 dependent mechanism . Virology 393(2):228-237
Daria, V .R ., Stricker, C., Bowman, R ., Redman, S. and Foret, S ., Wilson, S . and Burden, C. (2009) Bachor, H .A . (2009) Arbitrary multisite two-photon Characterizing the D2 Statistic: Word Matches in excitation in four dimensions . Applied Physics Letters Biological Sequences . Statistical Applications in 95(9):93701-93701 Genetics and Molecular Biology . 8(1): Article 43 de Wit, C . and Wölfle, S.E. (2009) Connexins in the French, H.J., Attenborough, R., Hardy, K., Shannon, Vasculature . In: Connexins: A Guide . A . Harris . and D . M.F., and Williams, R.B.H. (2009) Interindividual Locke (Eds .) Humana Press, New York pp . 457-468 variation in epigenomic phenomena in humans . Mammalian Genome 20(9-10):604-611 Dong, C ., Wong, M.-L. and Licinio, J. (2009) Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, Gready, J. and Zelensky, A. (2009) Routes in lectin CREB1, CRHR1 and NTRK2: association with major evolution: Case study of the C-type lectin-like depression and antidepressant response in Mexican- domains . In: The Sugar Code: Fundamentals of Americans . Molecular Psychiatry 14(12):1105-1118 Glycosciences . H .-J . Gabius (Ed .) Wiley-Blackwell Publishing Inc ., Weinheim pp . 329-346 Dulhunty, A., Wei, L. and Beard, N.A. (2009) Junctin - the quiet achiever . Journal of Physiology-London 587(13):3135-3137
The John Curtin School of Medical Research Annual Review 2009 97 Hamzah, J ., Altin, J.G., Herringson, T ., Parish, C.R., Jeon, Y .H ., Essue, B ., Jan, S ., Wells, R ., and Whitworth, Hammerling, G .J ., O’Donoghue, H . and Ganss, R . J.A. (2009) Economic hardship associated with (2009) Targeted Liposomal Delivery of TLR9 Ligands managing chronic illness: a qualitative inquiry . BMC Activates Spontaneous Antitumor Immunity in Health Services Research 9:182-182 an Autochthonous Cancer Model . Journal of Johnson, A .L ., Aravind, L ., Shulzhenko, N ., Morgun, A ., Immunology 183(2):1091-1098 Choi, S .Y ., Crockford, T .L ., Lambe, T ., Domaschenz, H., Huttley, G.A. (2009) Do genomic datasets resolve the Kucharska, E.M., Zheng, L .X ., Vinuesa, C.G., Lenardo, correct relationship among the placental, marsupial M .J ., Goodnow, C.C., Cornall, R .J . and Schwartz, and monotreme lineages? Australian Journal of R .H . (2009) Themis is a member of a new metazoan Zoology 57(3-4):167-174 gene family and is required for the completion of thymocyte positive selection . Nature Immunology Hutton, J .F ., Gargett, T ., Sadlon, T .J ., Bresatz, S ., Brown, 10(8):831-839 C .Y ., Zola, H ., Shannon, M.F., D’Andrea, R .J . and Barry, S . (2009) Development of CD4(+)CD25(+)FoxP3(+) Juelich, T., Sutcliffe, E., Denton, A ., He, Y.Q., Doherty, regulatory T cells from cord blood hematopoietic P .C ., Parish, C ., Turner, S .J ., Tremethick, D. and Rao, progenitor cells . Journal of Leukocyte Biology S. (2009) Interplay between Chromatin Remodeling 85(3):445-451 and Epigenetic Changes during Lineage-Specific Commitment to Granzyme B Expression . Journal of Ikeda, K. and Bekkers, J.M. (2009) Counting the Immunology 183(11):7063-7072 number of releasable synaptic vesicles in a presynaptic terminal . Proceedings of the National Karunasekara, Y., Dulhunty, A.F. and Casarotto, M.G. Academy of Sciences of the United States of (2009) The voltage-gated calcium-channel beta America 106(8):2945-2950 subunit: more than just an accessory . European Biophysics Journal with Biophysics Letters 39(1):75-81 Ikeda, K. and Bekkers, J.M. (2009) Two strategies for the efficient use of synaptic vesicles . Communicative Kho C .L ., Brown M .A ., Ong S.L.H. and Mangos G .J . & Integrative Biology. 2(6):1-4 (2009) The effect of arm circumference and blood pressure cuff size on blood pressure measurement in Ikin, J F. ., Sim, M .R ., McKenzie, D .P ., Horsley, K .W .A ., pregnancy . Obstetric Medicine 2(3):116-120 Wilson, E .J ., Harrex, W .K ., Moore, M .R ., Jelfs, P .L . and Henderson, S. (2009) Life satisfaction and quality Kimura, T ., Lueck, J .D ., Harvey, P .J ., Pace, S.M., Ikemoto, in Korean War veterans five decades after the war . N ., Casarotto, M.G., Dirksen, R .T . and Dulhunty, A.F. Journal of Epidemiology and Community Health (2009) Alternative splicing of RyR1 alters the efficacy 63(5):359-365 of skeletal EC coupling . Cell Calcium 45(3):264-274
Isomura, I ., Palmer, S., Grumont, R .J ., Bunting, K., Knott, M .L ., Hogan, S .P ., Wang, H ., Matthaei, K.I. and Hoyne, G., Wilkinson, N., Banerjee, A ., Proietto, Dent, L .A . (2009) FVB/N mice are highly resistant to A ., Gugasyan, R ., Li, W ., McNally, A ., Steptoe, R .J ., primary infection with Nippostrongylus brasiliensis . Thomas, R ,. Shannon, M.F. and Gerondakis, S . Parasitology 136(1):93-106 (2009) c-Rel is required for the development of Knott, M .L ., Matthaei, K.I., Foster, P .S . and Dent, thymic Foxp3(+) CD4 regulatory T cells . Journal of L .A . (2009) The roles of eotaxin and the STAT6 Experimental Medicine 206(13):3001-3014 signalling pathway in eosinophil recruitment and Jenne, C .N ., Enders, A ., Rivera, R ., Watson, S .R ., host resistance to the nematodes Nippostrongylus Bankovich, A .J ., Pereira, J .P ., Xu, Y ., Roots, C .M ., Beilke, brasiliensis and Heligmosomoides bakeri . Molecular J .N ,. Banerjee, A ., Reiner, S .L ., Miller, S .A ., Weinmann, Immunology 46(13):2714-2722 A .S ., Goodnow, C.C., Lanier, L .L ., Cyster, J .G ., and Koina, E ., Chaumeil, J ., Greaves, I.K., Tremethick, D.J. Chun, J . (2009) T-bet-dependent S1P(5) expression and Graves, J .A .M . (2009) Specific patterns of histone in NK cells promotes egress from lymph nodes and marks accompany X chromosome inactivation in a bone marrow . Journal of Experimental Medicine marsupial . Chromosome Research 17(1):115-126 . 206(11):2469-2481
98 The John Curtin School of Medical Research Annual Review 2009 Publications 2009
Lamb, T.D., Arendt, D . and Collin, S .P . (2009) Little, P .F .R ., Williams, R.B.H. and Wilkins, M .R . (2009) The evolution of phototransduction and eyes Inter-individual variation in expression: a missing Introduction . Philosophical Transactions of the Royal link in biomarker biology? Trends in Biotechnology Society B-Biological Sciences 364(1531):2791-2793 27(1):5-10
Lamb, T.D. (2009) Evolution of vertebrate retinal Liu, D., Hewawasam, R., Pace, S.M., Gallant, E.M., photoreception . Philosophical Transactions of Casarotto, M.G., Dulhunty, A.F. and Board, P.G. the Royal Society B-Biological Sciences (2009) Dissection of the inhibition of cardiac 364(1531):2911-2924 ryanodine receptors by human glutathione transferase GSTM2-2 . Biochemical Pharmacology Lambe, T ., Simpson, R .J ., Dawson, S ., Bouriez-Jones, 77(7):1181-1193 T ., Crockford, T .L ., Lepherd, M ., Latunde-Dada, G .O ., Robinson, H ., Raja, K .B ., Campagna, D .R ., Villarreal, Lobigs, M., Larena, M., Alsharifi, M ., Lee, E. and Pavy, G ., Ellory, J .C ,. Goodnow, C.C., Fleming, M .D ., McKie, M. (2009) Live Chimeric and Inactivated Japanese A T. . and Cornall, R .J . (2009) Identification of a Steap3 Encephalitis Virus Vaccines Differ in Their Cross- endosomal targeting motif essential for normal iron Protective Values against Murray Valley Encephalitis metabolism . Blood 113(8):1805-1808 Virus . Journal of Virology 83(6):2436-2445
Lee, S.H., Eldi, P., Cho, S.Y. and Rangasamy, D. Lobigs, M., Müllbacher, A., and Regner, M. (2009) CD4+ (2009) Control of chicken CR1 retrotransposons is and CD8+ T-Cell Immune Responses in West Nile Virus independent of Dicer-mediated RNA interference Infection . In: West Nile Encephalitis Virus Infection: pathway . BMC Biology 7(Article 53) Viral Pathogenesis and the Host Immune Response . Leitch, V .D ., Strudwick, X .L ., Matthaei, K.I., Dent, M S. . Diamond (Ed ). Springer, USA pp . 287-303 L A. . and Cowin, A .J . (2009) IL-5-overexpressing Mana, P., Fordham, S.A., Staykova, M.A., Correcha, mice exhibit eosinophilia and altered wound M., Silva, D., Willenborg, D.O. and Linares, D . (2009) healing through mechanisms involving prolonged Demyelination caused by the copper chelator inflammation . Immunology and Cell Biology cuprizone halts T cell mediated autoimmune 87(2):131-140 neuroinflammation . Journal of Neuroimmunology Liggins, J .R . and Gready, J.E. (2009) Putative Functional 210(1-2):13-21 Role for the Invariant Aspartate 263 Residue of Martin, R .E ., Marchetti, R .V ., Cowan, A.I., Howitt, S .M ., Rhodospirillum rubrum Rubisco . Biochemistry Broer, S . and Kirk, K . (2009) Chloroquine Transport 48(10):2226-2236 via the Malaria Parasite’s Chloroquine Resistance Lim, P.S., Hardy, K., Bunting, K.L., Ma, L., Peng, K.M., Transporter . Science 325(5948):1680-1682 Chen, X.X. and Shannon, M.F. (2009) Defining the chromatin signature of inducible genes in T cells . Matthaei, K.I. (2009) Current developments in Genome Biology 10(10):R107 genetically manipulated mice . In: Trends in Stem Cell Biology and Technology . H . Baharvand (Ed .) Humana Linterman, M.A., Rigby, R.J., Wong, R., Silva, D., Press Inc ., Germany pp . 123-136 Withers, D ,. Anderson, G ., Verma, N .K ., Brink, R ., Hutloff, A ., Goodnow, C.C. and Vinuesa, C.G. (2009) Matthaei, K.I. (2009) Identification of therapeutic drug Roquin Differentiates the Specialized Functions of targets through genetically manipulated mice: Are Duplicated T Cell Costimulatory Receptor Genes Cd28 we getting it right? Pharmacology and Therapeutics and Icos . Immunity 30(2):228-241 . 123(1):32-36
Linterman, M.A., Rigby, R.J., Wong, R.K., Yu, D., Brink, Morris, M.J., Craig, S .J ., Sutherland, T .M ., Board, P.G. R ,. Cannons, J .L ., Schwartzberg, P .L ., Cook, M.C., and Casarotto, M.G. (2009) Transport of glutathione Walters, G .D ., and Vinuesa, C.G. (2009) Follicular transferase-fold structured proteins into living helper T cells are required for systemic autoimmunity . cells . Biochimica Et Biophysica Acta-Biomembranes Journal of Experimental Medicine 206(3):561-576 1788(3):676-685
The John Curtin School of Medical Research Annual Review 2009 99 Murphy, R .M ,. Larkins, N .T ., Mollica, J .P ., Beard, N.A. Pardo, J ., Aguilo, J .I ., Anel, A ., Martin, P ., Joeckel, L ., and Lamb, G .D . (2009) Calsequestrin content and Borner, C ., Wallich, R ., Müllbacher, A., Froelich, C .J . SERCA determine normal and maximal Ca2+ storage and Simon, M .M . (2009) The biology of cytotoxic cell levels in sarcoplasmic reticulum of fast- and slow- granule exocytosis pathway: granzymes have evolved twitch fibres of rat . Journal of Physiology-London to induce cell death and inflammation . Microbes and 587(2):443-460 Infection 11(4):452-459
Murray-Rust, T .A ., Kerr, F .K ., Thomas, A .R ., Wu, T .N ., Pardo, J ., Gálvez, E .M ., Koskinen, A ., Simon, M .M ., Yongqing, T ., Ong, P .C ., Quinsey, N .S ., Whisstock, Lobigs, M., Regner, M ., and Müllbacher, A. (2009) J .C ., Wagenaar-Bos, I .C ., Freeman, C. and Pike, R .N . Caspase-Dependent Inhibition of Mousepox (2009) Modulation of the proteolytic activity of the Replication by gzmB . PloS One 4(10):7512-7522 complement protease C1s by polyanions: implications for polyanion-mediated acceleration of interaction Parish, C.R., Glidden, M .H ., Quah, B.J., and Warren, H.S. between C1s and SERPING1 . Biochemical Journal (2009) Use of the intracellular fluorescent dye CFSE 422:295-303 to monitor lymphocyte migration and proliferation . Current Protocols in Immunology 84:4 .9 .1-4 .9 .13 Navarro-Gonzalez, M.F., Grayson, T.H., Meaney, K.R., Cribbs, L .L . and Hill, C.E. (2009) Non-L-type voltage Parish, I .A ., Rao, S., Smyth, G .K ., Juelich, T., Denyer, G .S ., dependant calcium channels control vascular tone Davey, G .M ., Strasser, A . and Heath, W .R . (2009) The of the rat basilar artery . Clinical and Experimental molecular signature of CD8(+) T cells undergoing Pharmacology and Physiology 36(1):55-66 deletional tolerance . Blood 113(19):4575-4585
Nijnik, A ., Dawson, S ., Crockford, T .L ., Woodbine, L ., Paz, G .J ., Delibasi, T ., Erol, H .K ., Wong, M.-L. and Visetnoi, S ., Bennett, S ., Jones, M ., Turner, G .D ., Licinio, J. (2009) Cellular Immunity Before and After Jeggo, P .A ., Goodnow, C.C., and Cornall, R .J . (2009) Leptin Replacement Therapy . Journal of Pediatric Impaired lymphocyte development and antibody Endocrinology and Metabolism 22(11):1069-1074 class switching and increased malignancy in a murine Phipps, S ., Lam, C .E ., Kaiko, G .E ., Foo, S .Y ., Collison, A ., model of DNA ligase IV syndrome . The Journal of Mattes, J ., Barry, J ., Davidson, S ., Oreo, K ., Smith, L ., Clinical Investigation 119(6):1696-1705 Mansell, A ., Matthaei, K.I. and Foster, P .S . (2009) Ong, S.L.H., Zhang, Y. and Whitworth, J.A. (2009) Toll/IL-1 Signaling Is Critical for House Dust Mite- Mechanisms of dexamethason-induced hypertension . specific Th1 and Th2 Responses . American Journal of Current Hypertension Review 5(1):61-74 Respiratory and Critical Care Medicine 179(10): 883-893 Ong, S.L.H., Zhang, Y., Sutton, M. and Whitworth, J.A. (2009) Hemodynamics of dexamethasone-induced Phipps, S ., Hansbro, N ., Lam, C .E ., Foo, S .Y ., Matthaei, hypertension in the rat . Hypertension Research K.I. and Foster, P .S . (2009) Allergic sensitization is 32(10):889-894 enhanced in early life through toll-like receptor 7 activation . Clinical and Experimental Allergy Palmer, L.M. and Stuart, G.J. (2009) Membrane 39(12):1920-1928 Potential Changes in Dendritic Spines during Action Potentials and Synaptic Input . Journal of Poon, I.K.H., Olsson, A .K ., Hulett, M.D. and Parish, C.R. Neuroscience 29(21):6897-6903 (2009) Regulation of histidine-rich glycoprotein (HRG) function via plasmin-mediated proteolytic Papathanasiou, P., Attema, J .L ., Karsunky, H ., Hosen, cleavage . Biochemical Journal 424:27-37 (Part 1) N ., Sontani, Y., Hoyne, G.F., Tunningley, R ., Smale, S .T ., and Weissman, I .L . (2009) Self-Renewal of the Pouliquin, P., Pace, S.M. and Dulhunty, A.F. (2009) In Long-Term Reconstituting Subset of Hematopoietic vitro modulation of the cardiac ryanodine receptor Stem Cells is Regulated by Ikaros. Stem Cells 27(12): activity by Homer1 . Pflugers Archiv-European 3082-3092 Journal of Physiology 458(4):723-732
100 The John Curtin School of Medical Research Annual Review 2009 Publications 2009
Pouliquin, P. and Dulhunty, A.F. (2009) Homer and the Seymour, V.A.L., Everitt, A.B. and Tierney, M.L. (2009) ryanodine receptor . European Biophysics Journal Differential Drug Responses on Native GABA(A) with Biophysics Letters 39(1):91-102 Receptors Revealing Heterogeneity in Extrasynaptic Populations in Cultured Hippocampal Neurons . Ranasinghe, C. and Ramshaw, I.A. (2009) Immunisation Journal of Membrane Biology 227(3):111-122 route-dependent expression of IL-4/IL-13 can modulate HIV-specific CD8(+) CTL avidity . European Stapelberg, M .P .F ., Williams, R.B.H., Byrne, S .N . and Journal of Immunology 39(7):1819-1830 Halliday, G .M . (2009) The Alternative Complement Pathway Seems to be a UVA Sensor that Leads Ranasinghe, C. and Ramshaw, I.A. (2009) Genetic to Systemic Immunosuppression . Journal of heterologous prime-boost vaccination strategies for Investigative Dermatology 129(11):2694-2701 improved systemic and mucosal immunity . Expert Review of Vaccines 8(9):1171-1181 Sutcliffe, E.L., Parish, I .A ., He, Y.Q., Juelich, T., Tierney, M.L., Rangasamy, D., Milburn, P.J., Parish, C.R., Randall, K.L., Lambe, T ., Johnson, A ., Treanor, B ., Tremethick, D.J. and Rao, S. (2009) Dynamic Histone Kucharska, E., Domaschenz, H., Whittle, B., Tze, Variant Exchange Accompanies Gene Induction in T L.E., Enders, A., Crockford, T .L ., Bouriez-Jones, T ., Cells . Molecular and Cellular Biology 29(7): Alston, D ., Cyster, J .G ., Lenardo, M .J ., Mackay, F ., 1972-1986 Deenick, E K. ., Tangye, S .G ., Chan, T .D ., Camidge, T ., Brink, R ., Vinuesa, C.G., Batista, F .D ., Cornall, R .J . and Sutherland, A.P.R., Van Belle, T ., Wurster, A .L ., Suto, Goodnow, C.C. (2009) Dock8 mutations cripple B A ., Michaud, M ., Zhang, D ., Grusby, M .J . and von cell immunological synapses, germinal centers and Herrath, M . (2009) Interleukin-21 Is Required for long-lived antibody production . Nature Immunology the Development of Type 1 Diabetes in NOD Mice . 10(12):1283-1291 Diabetes 58(5):1144-1155
Regner, M., Pavlinovic, L., Koskinen, A., Young, N., Sutherland, A.P.R., Zhang, H ., Zhang, Y ., Michaud, Trapani, J .A ,. and Müllbacher, A. (2009) Cutting M ., Xie, Z .F ., Patti, M .E ., Grusby, M .J . and Zhang, Edge: Rapid and Efficient In Vivo Cytotoxicity by W .J . (2009) Zinc Finger Protein Zbtb20 Is Essential Cytotoxic T Cells is Independent of Granzymes A and for Postnatal Survival and Glucose Homeostasis . B1 . Journal of Immunology 183(1):37-40 Molecular and Cellular Biology 29(10):2804-2815
Reierson, G .W ., Mastronardi, C.A., Licinio, J. and Wong, Tae, H.S., Norris, N.C., Cui, Y.F., Karunasekara, Y., M.-L. (2009) Repeated antidepressant therapy Board, P.G., Dulhunty, A.F. and Casarotto, M.G. increases cyclic GMP signaling in rat hippocampus . (2009) Molecular recognition of the disordered Neuroscience Letters 466(3):149-153 dihydropyridine receptor II-III loop by a conserved spry domain of the type 1 ryanodine receptor . Reuter, F ., Bade, S ., Hirst, T.R. and Frey, A . (2009) Clinical and Experimental Pharmacology and Bystander protein protects potential vaccine- Physiology 36(3):346-349 targeting ligands against intestinal proteolysis . Journal of Controlled Release 137(2):98-103 Tae, H., Casarotto, M.G. and Dulhunty, A.F. (2009) Ubiquitous SPRY domains and their role in the Sachdev, P .S ., Parslow, R ., Wen, W ., Anstey, K .J . and skeletal type ryanodine receptor . European Biophysics Easteal, S. (2009) Sex differences in the causes and Journal with Biophysics Letters 39(1):51-59 consequences of white matter hyperintensities . Neurobiology of Aging 30(6):946-956 Tangye, S .G ., Cook, M.C. and Fulcher, D .A . (2009) Insights into the Role of STAT3 in Human Sandow, S L. ., Haddock, R.E., Hill, C.E., Chadha, P .S ., Kerr, Lymphocyte Differentiation as Revealed by the P .M ., Welsh, D .G . and Plane, F . (2009) What’s where Hyper-IgE Syndrome . Journal of Immunology and why at a vascular myoendothelial microdomain 182(1):21-28 signalling complex . Clinical and Experimental Pharmacology and Physiology 36(1):67-76
The John Curtin School of Medical Research Annual Review 2009 101 Publications 2009
Theodoratos, A., Tu, W.J., Cappello, J., Blackburn, A.C., Worden, A .Z ., Lee, J .H ., Mock, T ., Rouze, P ., Simmons, Matthaei, K.I. and Board, P.G. (2009) Phenylalanine- M .P ., Aerts, A .L ., Allen, A .E ., Cuvelier, M .L ., Derelle, induced leucopenia in genetic and dichloroacetic E ., Everett, M .V ., Foulon, E ., Grimwood, J ., Gundlach, acid generated deficiency of glutathione transferase H ., Henrissat, B ., Napoli, C ., McDonald, S .M ., Parker, Zeta . Biochemical Pharmacology 77(8):1358-1363 M .S ., Rombauts, S ., Salamov, A ., Von Dassow, P ., Badger, J .H ., Coutinho, P .M ., Demir, E ., Dubchak, I ., Vinuesa, C.G., Rigby, R.J. and Yu, D. (2009) Logic and Gentemann, C ., Eikrem, W ., Gready, J.E., John, U ., Extent of miRNA-Mediated Control of Autoimmune Lanier, W ., Lindquist, E .A ., Lucas, S ., Mayer, K .F .X ., Gene Expression . International Reviews of Moreau, H ., Not, F ., Otillar, R ., Panaud, O ., Pangilinan, Immunology 28(3-4):112-138 J ., Paulsen, I ., Piegu, B ., Poliakov, A ., Robbens, S ., Schmutz, J ., Toulza, E ., Wyss, T ., Zelensky, A ., Zhou, Vinuesa, C.G., Sanz, I . and Cook, M.C. (2009) K ., Armbrust, E .V ., Bhattacharya, D ., Goodenough, Dysregulation of germinal centres in autoimmune U .W ., Van de Peer, Y ., and Grigoriev, I .V ., 2009, Green disease . Nature Reviews Immunology 9(12):845-857 Evolution and Dynamic Adaptations Revealed by Wang, J., Lee, S., Teh, C.E.Y., Bunting, K., Ma, L. and Genomes of the Marine Picoeukaryotes Micromonas . Shannon, M.F. (2009) The transcription repressor, Science 324(5924):268-272 ZEB1, cooperates with CtBP2 and HDAC1 to Xiao, J .H ., Wong, A .W ., Willingham, M .M ., Kaasinen, suppress IL-2 gene activation in T cells . International S.K., Hendry, I.A., Howitt, J ., Putz, U ., Barrett, G .L ., Immunology 21(3):227-235 Kilpatrick, T .J . and Murray, S .S . (2009) BDNF Exerts Wang, Y., Chaudhri, G., Jackson, R.J. and Karupiah, Contrasting Effects on Peripheral Myelination of G. (2009) IL-12p40 and IL-18 Play Pivotal Roles in NGF-Dependent and BDNF-Dependent DRG Neurons . Orchestrating the Cell-Mediated Immune Response Journal of Neuroscience 29(13):4016-4022 to a Poxvirus Infection . Journal of Immunology Yu, D., Rao, S., Tsai, L .M ., Lee, S.K., He, Y.Q., Sutcliffe, 183(5): 3324-3331 E.L., Srivastava, M., Linterman, M., Zheng, L., Webb, D.C . (2009) Response to Comment on “Ym1/2 Simpson, N., Ellyard, J.I., Parish, I.A., Ma, C .S ., Li, Promotes Th2 Cytokine Expression by Inhibiting Q .J ., Parish, C.R., Mackay, C .R . and Vinuesa, C.G. 12/15(S)-Lipoxygenase: Identification of a Novel (2009) The Transcriptional Repressor Bcl-6 Directs T Pathway for Regulating Allergic Inflammation” . Follicular Helper Cell Lineage Commitment . Immunity Journal of Immunology 183(10):6039-6040 31(3):457-468
Wei, L., Gallant, E.M., Dulhunty, A.F. and Beard, Yu, D. and Vinuesa, C.G. (2009) Roquin Defects Reveal N.A. (2009) Junctin and triadin each activate a Role for the microRNA Machinery in Regulating skeletal ryanodine receptors but junctin alone Autoimmunity . In: The Epigenetics of Autoimmune mediates functional interactions with calsequestrin . Disease . M . Zouali (Ed .), John Wiley & Sons Ltd ., International Journal of Biochemistry and Cell Chichester, U .K . pp . 261-274 Biology 41(11):2214-2224 Zhang, Y., Wu, J.H.Y., Vickers, J.J., Ong, S.L.H., Temple, Wei, L., Hanna, A.D., Beard, N.A., and Dulhunty, S .E .L ., Mori, T .A ., Croft, K .D . and Whitworth, J.A. A.F. (2009) Unique isoform-specific properties of (2009) The role of 20-hydroxyeicosatetraenoic acid in calsequestrin in the heart and skeletal muscle . Cell adrenocorticotrophic hormone and dexamethasone- Calcium 45(5): 474-484 induced hypertension . Journal of Hypertension 27(8):1609-1616 Wölfle, S.E., Schmidt, V .J ., Hoyer, J ., Köhler, R ., and de Wit, C . (2009) Prominent role of KCa3 .1 in endothelium-derived hyperpolarizing factor- type dilations and conducted responses in the microcirculation in vivo . Cardiovascular Research 82(3):476-483
102 The John Curtin School of Medical Research Annual Review 2009 Patents 2009
Jill Gready and Babu Kannappan Steven Weiss
Process for generation of protein and uses thereof . CA2661448 Patent Applications (No .) Reducing myocardial damage and the incidence of arrhythmia arising from loss, reduction or interruption Argentina (P070104488), Australia (2007306926), in coronary blood flow . Brazil (PI0717758 .5), Canada (2665766), China AU2009900789 (200780045611 .6), Europe (07815347 .5), India (02498/ CHENP/09), USA (12/422190) Positive Inotrope, Positive Lusitrope and Treatment for Related Diseases . AU2009900848 Positive Inotrope Agent, Positive Lusitrope Agent and Agent for the Treatment of Related Diseases . AU2009903235 Treatment of cell, tissue and organ damage and associated pain .
The John Curtin School of Medical Research Annual Review 2009 103 Presentations 2009
Dr N . Beard Professor A . Dulhunty The C-terminus of skeletal muscle calsequestrin is The elusive ryanodine receptor: Ca2+ Signalling, essential for calsequestrin function and RyR regulation Mobility and Heart Beat The Curtin Conference on Ion Channels and Asian Biophysical Association, Hong Kong, China Transporters, Canberra, ACT Calsequestrin regulation of skeletal RyR1, coupled gating Dr E M. . Bertram of RyR1 channels in the presence of calsequestrin, and Linking causal relationships between genes and different interactions with cardiac RyR2 phenotypes of the immune system through large scale Gordon Conference on Excitation-Contraction ENU mutagenesis of the mammalian genome Coupling, Waterville Valley, NH, US Fudan University, Shanghai, China Peter Gage: A Wonderful Life in Science The Curtin Conference on Ion Channels and Professor P .G . Board Transporters, Canberra, ACT The γ-Glutamylcyclotransferase family, its role in the The Ryanodine Receptor – its role in heart disease regulation of glutathione homeostasis and other Cardiac Society of Australia and New Zealand novel pathways Chair; The Robertson Prize Lecture University of Sydney, Sydney, NSW The 33rd Annual Meeting of the Australian Society for GSTs, are we there yet? Biophysics, Ballarat, VIC Scientific Achievement Award Lecture, International Society for the Study of Xenobiotics, Bangkok, Professor S . Easteal Thailand The Role of Genetics γ-Glutamylcyclotransferase and the regulation of Workshop on the Design of the Athlete, Australian glutathione homeostasis Institute of Sport and University of Canberra, International Society for the Study of Xenobiotics, Canberra, ACT Lisbon, Portugal Short tandem repeat variation in human evolution Dr J-D . Breton and health Lorne Genome Conference, Lorne, VIC Regulation of neuronal excitability in the barrel cortex: role of GABAergic-mediated inhibition and Dr A . Enders sensory deprivation Genetic control of T cell differentiation Laboratoire Neurobiologie des Canaux Coniques, 39th Annual Scientific Meeting of the Australasian Universitie de la Mediterranee, Marseille, France Society for Immunology, Gold Coast, QLD Dr M . Casarotto Dr C . Freeman Biophysical interactions of the skeletal II-III loop Roles of Heparanase and Heparan Sulfate in Gordon Conference on Excitation-Contraction Type 1 Diabetes Coupling, Waterville Valley, NH, US Biochemical Society 67th Harden Conference: Investigations into the mechanisms regulating cell "Decoding the biology of heparan sulphate uptakes of GSTs proteoglycans" Robinson College, Cambridge, UK The Curtin Conference on Ion Channels and Transporters, Canberra, ACT Professor C .C . Goodnow Therapeutic Design, Targets, Strategies and Translating DNA Sequence into Immunological Systems New Molecules National Institutes of Allergy and Infectious Diseases, Monash Institute of Pharmaceutical Sciences, Monash National Institutes of Health, Bethesda, MD, US University, Melbourne, VIC The dendritic cell marker CD83 opposes the downregulation of MHC II and CD86 by MARCH1 Dr J . Chen ubiquitin ligase and IL-10 Mechanism and function of IL-3 receptor α in National Institutes of Health, Bethesda, MD, US differentiation of mouse hematopoietic cells International Union of Biochemistry and Molecular Biology World Congress, Shanghai, China
104 The John Curtin School of Medical Research Annual Review 2009 Presentations 2009
Systems biology approaches in immunology Professor C .E Hill. 22nd Annual Spring Meeting Canadian Society for How important is myoendothelial coupling to the Immunology, Whistler, BC, Canada control of vascular tone? Checkpoints in the immune response to prevent Symposium Speaker: "Cellular mechanisms that autoimmune disease initiate and coordinate changes in vascular tone", Royal Society New Fellows Seminar, London, UK Experimental Biology, New Orleans, LA, US Immunological Tolerance Myoendothelial coupling: What is the relevance to Postgraduate Lecture Series, The Walter & Eliza Hall vascular function? Institute, Melbourne, VIC Weill Cornell Medical College, Doha, Qatar Translating DNA sequence data into understanding of New Targets for Hypertension? Physiological and immunological systems transgenic approaches Jonathan Sprent Oration 2009, Brisbane Immunology Novartis Medical Practioners Dinner, Canberra, ACT Group, Gold Coast, QLD Dr G .F . Hoyne Mendel’s long tail: Implications of quantitative phenotypes in heterozygous carriers of recessive T cell homeostasis is regulated by a program of mRNA syndrome mutations alternative splicing mediated by heterogeneous Vern Chapman Lecture, International Mammalian nuclear ribonuclear protein L-like(hnRNPLL) Genome Society Meeting, La Jolla, CA, US 39th Annual Scientific Meeting of the Australasian Society for Immunology, Gold Coast, QLD 39th Annual Scientific Meeting of the Australasian Society for Immunology, Gold Coast, QLD Studies on the genetics of autoimmune disease ASI Workshop on Immunity, JCSMR, ANU, Canberra, Consequences of Genetic Variation in Lymphocyte ACT Signalling Pathways Monash University, Melbourne, VIC A new mouse model for fatty liver disease and type 2 diabetes Signalling life vs death in germinal centres and thymus School of Health Sciences, University of Notre Dame 13th Australasian Autoimmunity Workshop, Australia, Fremantle, WA Adelaide, SA From KMA to ANU...a lifelong fascination with B cells Dr G .A . Huttley thanks to RLR Measurement of evolutionary processes using Comparative and Molecular Immunobiology continuous time Markov models Symposium: A celebration of the contributions of Department of Chemistry and Biochemistry, University Emeritus Professor Robert L . Raison, Sydney, NSW of Colorado, Boulder, CO, US Professor J .E . Gready Measurement of evolutionary processes using Status of options for improving photosynthetic continuous time Markov models capacity through promotion of performance of Rubisco: Annual Conference of the Genetics Society of Rubisco re-engineering and chloroplast transformation Australasia, Brisbane, QLD Workshop: Applying photosynthesis research to PyCogent: an integrated framework for improvement of food crops, ANU, Canberra, ACT computational genomics Status of options for improving photosynthetic Bioinformatics Australia Conference, Melbourne, VIC capacity through promotion of performance of Rubisco: Exploiting natural diversity of Rubisco from Associate Professor G . Karupiah germplasm collections Protective immunity to secondary poxvirus infections Workshop: Applying photosynthesis research to 39th Annual Scientific Meeting of the Australasian improvement of food crops, ANU, Canberra, ACT Society for Immunology, Gold Coast, QLD What a difference one or two water molecules make Viral Immunology to an enzymic mechanism: the final solution to the 10th FIMSA Advanced Immunology Training Course, mechanism of dihydrofolate reductase? Tangalooma Island Resort, QLD Australian Society for Biophysics Conference, Ballarat, VIC
The John Curtin School of Medical Research Annual Review 2009 105 Dr M . Kole Antidepressants: Friend or Foe Axonal Kv7 channels control membrane potential stability Australasian Society for Psychiatric Research Australian Neuroscience Society Annual Conference, Conference, Manning Clark Center, ANU, Canberra, ACT Canberra, ACT Chair: Early Career Research Colloquium Australasian Society for Psychiatric Research Professor T . Lamb Conference, Manning Clark Center, ANU, Canberra, ACT Rods, cones and bipolar cells Chronic Fluoxetine Treatment Increases Daytime Keynote Lecture, University of California Davis Vision Melatonin Synthesis in the Rodent Research Symposium, University of California, Davis, 48th Annual Meeting of the American College of CA, US Neuropsychopharmacology, Hollywood, FL, US Evolution of the vertebrate eye Keynote Lecture, University of California Davis Vision Dr M . Lobigs Research Symposium, University of California, Davis, Flavivirus vaccines CA, US Symposium: Cutting Edge Vaccines for the 21st Evolutionary origin of the vertebrate eye Century, Flinders University, Adelaide, SA and photoreceptors The Australian encephalitis - Japanese School of Medical Science, University of New South encephalitis vaccination dilemma: risks and benefits Wales, Sydney, NSW of cross-protective immunisation against The molecules of vision and their evolution low-disease-incidence flaviviruses Keynote Lecture, Molecular Frontiers Symposium, Symposium: Emerging Infectious Diseases: the Global The Royal Swedish Academy of Sciences, Perspective, ANU, Canberra, ACT Stockholm, Sweden Dr C . Mastronardi Evolution of the eye Central and peripheral transcriptional responses Public lecture: Vision Science Lecture Series, during LPS-induced inflammatory stress Questacon, Canberra, ACT 48th Annual Meeting of the American College of Evolution of vision Neuropsychopharmacology, Hollywood, FL, US Keynote Lecture, Biosciences Research, Victorian Professor K . Matthaei Department of Primary Industries, Melbourne, VIC Stem Cells and Regenerative Medicine Professor J . Licinio Plenary Lecture: Women’s Section for Sciences and Medical Science, King Saud University, Riyadh, The The Genomic Marker Payoff Kingdom of Saudi Arabia 1st Annual Meeting on Personalised Medicine for the Brain: Current Realities and Opportunities, Lessons from animal models for stem cell research Washington, DC, US Department of Anatomy, King Saud University and King Khalid Medical School, Riyadh, The Kingdom of T1-Related Immunity Genes as Candidates in Saudi Arabia Major Depression Symposium: Immune/Brain Cell Systems and Regenerative Medicine via Stem Cells Infectious Agents, The 10th Psychoimmunology Expert University of the Third Age, Canberra, ACT Meeting, Reisenberg, Germany Stem Cell Regenerative Medicine: Lessons from Symposium Chair Animal Models? Immune Cell and Antibody Alterations, The 10th Plenary lecture: 1st International Conference on Psychoimmunology Expert Meeting, Reisenberg, Germany Stem Cells and Regenerative Medicine in Riyadh, The Depression and Obesity: What to do when one Feels Kingdom of Saudi Arabia Sad and Fat Genetically modified mice: A powerful tool with ANU Wellbeing Week, ANU, Canberra, ACT unsuspected caveats Keynote Address: Pharmacogenomics of Depression as Weill Cornell Medical School, Doha, Qatar a Model of Translation Research in Psychiatry The Pros and Cons of Eugenics Australasian Society for Psychiatric Research Café Scientifique, Telopea Park High School, Canberra, ACT Conference, Manning Clark Center, ANU, Canberra, ACT
106 The John Curtin School of Medical Research Annual Review 2009 Presentations 2009
Dr P . Papathanasiou PKC-theta physically associates with chromatin ENU Stem Cell Mutants in T cells Icahn Medical Institute, Mount Sinai School of Agilent Technologies microarray seminar series, Medicine, New York, NY, US University of Queensland, St Lucia, QLD Agilent Technologies microarray seminar series, New York University Medical Center, New York, NY, US University of Sydney, Sydney, NSW Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, US Dr C . Ranasinghe Institute for Molecular Bioscience, University of HIV Vaccines Progress and Pitfalls Queensland, Brisbane, QLD Emerging Infectious Diseases: the Global Perspective, ANU, Canberra, ACT World Day of Immunology, Canberra, ACT Recombinant HIV-1 vaccines that co-express IL-13 Professor C R. . Parish inhibitors can enhance HIV-specific CD8+ T cell avidity From carbohydrate-based drugs to vaccines: A and protective immunity. multifaceted approach to cancer control 39th Annual Scientific Meeting of the Australasian Society for Immunology, Gold Coast, QLD Bosch Institute Annual Scientific Meeting: New Horizons in Biomedical Research, University of Sydney, Dr D . Rangasamy Sydney, NSW Genomin instability: Hip hopping of L1 Antigen receptor sharing: A new immunological retrotransposon out of control in cancer cells paradigm Duke-NUS Graduate Medical School, Comparative and Molecular Immunobiology Singapore, Singapore Symposium, University of Technology Sydney, Dr C . Raymond Sydney, NSW Role of NR2B Subunit-Containing NMDA Receptors in Cancer immunotherapy: Fact or Fiction Different Forms of LTP Gordon Ada Oration, Tumour Immunology Workshop, Australasian Winter Conference on Brain Research, 39th Annual Scientific Meeting of the Australasian Queenstown, NZ Society for Immunology, Gold Coast, QLD Memories are not always forever: Multiple forms of Angiogenesis inhibitors long-term potentiation at a single synapse Canberra Region Annual Scientific Meeting, Canberra, ACT Brain and Mind Research Institute, University of The skin as an immunological barrier to pathogens Sydney, Sydney, NSW Public Lecture, University of the Third Age, Compartmentalised calcium signaling supports Canberra, ACT multiple forms of long-term potentiation Anderson Stuart Seminars, Departments of Anatomy The role of heparanase and heparan sulfate in health and Physiology, University of Sydney, Sydney, NSW and disease Children’s Medical Research Institute, Sydney, NSW Compartment-specific neuronal calcium signals trigger different forms of long-term potentiation Role of heparanase and heparan sulfate in Symposium: Australian Neuroscience Society Annual type 1 diabetes Conference, Canberra, ACT Baker IDI Heart and Diabetes Institute, Melbourne, VIC Dr Stuart Read Mrs A . Prins The NHMRC Australian Phenome Bank Co-presenter: Surgical Cut-Up Workshop, South Victorian Animal Managers Group, Monash University, West Division of the Australian Institute of Medical Melbourne, VIC Scientists Annual Conference, Orange, NSW Vascular Biology Workshop, ANU, Canberra, ACT Dr S . Rao Murdoch Children's Research Institute, Melbourne, VIC Global ChIP-on-chip analysis in resting and activated T cells Agilent Technologies microarray seminar series, ANU, Canberra, ACT
The John Curtin School of Medical Research Annual Review 2009 107 Dr C .J . Simeonovic One point mutation, many autoimmune diseases Improving Beta cell survival by ECM preservation Mon-Man III workshop: Genetically modified mouse The 27th Annual Scientific Meeting of the Transplantation models of human disease, Government House, Society of Australia and New Zealand, Canberra, ACT Melbourne, VIC Professor G . Stuart Associate Professor H .S . Warren The action potential NK cells in Transplantation Plenary Lecture: The Australian Neuroscience Society Transplantation Society of Australia and New Zealand Annual Conference, Canberra, ACT Postgraduate Training Course, Canberra, ACT Local network interactions in the cortex Professor J .A . Whitworth Structure and Function of Neural Circuits, Address Obergurgl, Austria CAPSE 10th Anniversary Meeting on Global Health, The action potential ANU, Canberra, ACT Spring School in Systems Neuroscience, Kyoto, Japan Perspectives in Chronic Kidney Disease Dendrites Adelaide, SA Okinawa Computational Neuroscience Course, Intellectual property reform Okinawa, Japan Melbourne, VIC The action potential Dinner Oration Dartmouth Medical School, Dartmouth College, Menzies Research Institute, Hobart, TAS Hanover, NH, US Global health research Dr M .L . Tierney Annual Meeting of the WHO Advisory Committee on Health Research, Panama City, Panama GABAA Receptors; Beyond the Synapse The University of New South Wales, Sydney, NSW Dr S .E . Wölfle TRP channels provide the depolarisation initiating GABAA Receptor Cross talk The Curtin Conference on Ion Channels and vasomotion and vessel tone in cerebral resistance arteries Transporters, Canberra, ACT Experimental Biology, New Orleans, LA, US Voltage dependent calcium channels provide the Dr C .G . Vinuesa mechanism underlying long distance propagation of Tfh cell development and consequences of dysregulation vasodilation in vivo Microanatomy of Immune Responses in Health and Eccles Seminar Series, Neuroscience Program, ANU, Disease, University of Birmingham, Birmingham, UK Canberra, ACT Bcl-6 directs Tfh cell differentiation RCAI-JSI International Symposium on Immunology, Professor M-L . Wong RIKEN Research Center for Allergy and Immunology Role of Inflammation in Major Depressive Disorder: Clinical and Genetic Evidence RCAI, Yokohama, Japan Australasian Society for Psychiatric Research T follicular helper cells in systemic autoimmunity Workshop: Neurobiology of Stress and Emotion EMBO Conference – Co-sponsored by ENII: Tackling Regulation, Manning Clark Center, ANU, Canberra, ACT and Imaging the Complexity of the Immune System, Capo Caccia, Sardinia, Italy Dru . Z . W Pre-mRNA alternative splicing is essential in Immunogenetics of Antibody Responses regulating T cell immunity and homeostasis 2009 Federation of Immunological Societies of Keystone Symposia: Human Immunology and Australasia (FIMSA) Advanced Immunology Training Immunodeficiency, Beijing, China Course, Tangalooma Island, QLD The Roquin family of E3 ligases regulate their targets Dr Y . Zhang via repression of mRNAs The role of 20-hydroxyeicosatetraenoic acid (20-HETE) 4th Barossa Meeting: Cell Signalling in Cancer and in glucocorticoid-induced hypertension Development, Barossa Valley, SA Cardiology Unit, The Queen Elizabeth Hospital, Adelaide, SA
108 The John Curtin School of Medical Research Annual Review 2009 Student presentations 2009
Student presentations 2009
Addis, S., Bettadapura, J ,. Lee, E . and Lobigs, M . Hanna, A., Janczura, M ,. Dulhunty, A F. . and Beard, N A. . Genetic and functional analysis of the proteolytic Ryanodine receptor dysfunction in anthracycline- cleavage at the junction of the NS1 and NS2A induced cardiotoxicity proteins of Murray Valley encephalitis virus Gordon Conference on Excitation-Contraction Australian Society for Medical Research Young Coupling, Waterville Valley, NH, US Investigator’s Forum, Canberra Region Annual Scientific Meeting, Canberra ACT Henderson, J., Cho, V ,. Garvican, L ,. Gray, B ,. Gore, C ,. Williams, R . and Easteal, S . Chen, G. Altered transcriptional responses in elite endurance Understanding the mechanisms that activate LINE-1 athletes exposed to moderate altitude in breast cancer cells Biomolecules for Quality of Life 9th Annual Meeting of The Australian Microarray & The 21st International Union Biochemistry and Associated Technology Association: “High-Throughput Molecular Biology International Congress and 12th Genomic Technologies”, Katoomba, NSW FAOBMB Congress of Biochemistry and Molecular Biology, Shanghai, China Hewawasam, R.P., Liu D ., Casarotto M .G ., Board P .G . and Dulhunty A F. . Cho, V., Luo, O ,. Henderson, J ,. Easteal, S . and Williams, R . Activity of GSTM2C terminus and its mutants on A gene set approach to measuring inter-individual cardiac ryanodine receptor Ca2+ release channels in variation in gene expression the presence and absence of ATP Annual Conference of the Genetics Society of Gordon Conference on Excitation-Contraction Australasia, Brisbane, QLD Coupling, Waterville Valley, NH, US
Chua, A.H. Hewawasam, R.P., Liu D ,. Casarotto M G. ,. Board P G. . and Role of sympathetic, parasympathetic and sensory Dulhunty A F. . nerves of the cerebral circulation Destabilization of the interaction between helix 6 Kioloa Neuroscience Colloquium, Kioloa, NSW and cardiac ryanodine receptor reduces the inhibitory action of GSTM2-2 Coupland L.A. The Curtin Conference on Ion Channels and Inhibitory receptors control Fc-gamma receptor- Transporters, Canberra, ACT mediated ITP: implications for pathological autoantibodies Johnstone, V.P.A. 39th Annual Scientific Meeting of the Australasian Alterations in vesicle turnover rates associated with Society for Immunology, Gold Coast, QLD three different forms of long-term potentiation in the hippocampus Cui, Y., Norris, N ,. Karunasekara, Y ,. Board, P G. ,. Dulhunty, A F. . Australasian Winter Conference on Brain Research, and Casarotto, M G. . Queenstown, NZ Domain interactions involving the skeletal DHPR and RyR Karunasekara, Y., Gallant, E .M ., Board, P .G ., and Gordon Conference on Excitation-Contraction Casarotto, M .G . Coupling, Waterville Valley, NH, US Interactions of the skeletal DHPR Ca2+ channel Beta subunit with the II-III loop of the alpha 1s subunit Feng, J., Easteal, S . and Huttley, G A. . Gordon Conference on Excitation-Contraction A genome-wide scan reveals candidate loci Coupling, Waterville Valley, NH, US associated with differential viability between the sexes in humans Annual Conference of the Genetics Society of Australasia, Brisbane, QLD
The John Curtin School of Medical Research Annual Review 2009 109 Kuo, I.Y. Seymour, V.A.L., Kuo, I Y. ,. Cribbs, L L. . and Hill, C E. . Aspects of calcium signalling in cerebral vessels Characterization of voltage dependent calcium Department of Pharmacology, University of Virginia, channel subtypes in rat basilar arteries Charlottesville, VA, US The Curtin Conference on Ion Channels and Calcium channels in cerebral vessels: more than Transporters . Canberra, ACT one subtype? Eccles Seminar Series, Neuroscience Program, ANU, Teh C. Canberra, ACT Combinatorial defects in central and peripheral tolerance checkpoints precipitate autoimmune Larena, M., Lee, E ,. Regner, M ,. and Lobigs, M . pancreatitis and sialitis Role of Cytotoxic CD8+ T cells in Primary Japanese 39th Annual Scientific Meeting of the Australasian Encephalitis Virus Infection Society for Immunology, Gold Coast, QLD Australian Society for Medical Research Young Partial inhibition of PKCß disrupts T cell independent Investigator’s Forum, Canberra Region Annual type 2 antibody responses Scientific Meeting, Canberra, ACT Australasian Society for Immunology (ACT Branch) Symposium, Canberra, ACT Lee, S-H. Functional analysis of L1 retrotransposable elements Vassilieva, T., Chakka, N ,. Gready, J . E . in mouse genome Origin and evolution of new functions: example of the Epigenetics 2009, Melbourne, VIC prion-protein family genes, PRNP and PRND . Darwin Conference: Evolution – the Lindsay, H. and Huttley, G A. . experience, Melbourne, VIC Do sex-specific differences in DNA methylation and transcription levels contribute to male-biased evolution? Ying, H., Epps, J ,. Williams, R . and Huttley, G A. . Evolution – The Festival, Melbourne, VIC The influence of epigenetic state on genetic variation Annual Conference of the Genetics Society of Australasian Microarray & Associated Technologies Australasia, Brisbane, QLD Association Conference, Katoomba, NSW Evidence that localised variation in primate sequence Randall, K. divergence arises from an influence of nucleosome Humoral immunodeficiency associated with placement on DNA repair DOCK8 mutations Annual Conference of the Genetics Society of 39th Annual Scientific Meeting of the Australasian Australasia, Brisbane, QLD Society for Immunology, Gold Coast, QLD
Seymour, V.A.L., Curmi, J . and Tierney, M L. . GABAA receptors use a general mechanism to generate high conductance channels The Curtin Conference on Ion Channels and Transporters, Canberra, ACT
110 The John Curtin School of Medical Research Annual Review 2009 Our Community
JCSMR is committed to maintaining contact with our past staff and students through our Alumni and Friends network. We strive to strengthen our ties with our local Canberra community through visits and speaking engagements.
For information about joining this growing network of friends and supporters, please contact our Public Affairs Manager:
Dr Madeleine Nicol E: [email protected] T: +61 2 6125 2577 F: +61 2 6125 2337
The John Curtin School of Medical Research Annual Review 2009 Our community 2009
Flowcytometry Workshop at JCSMR The Inaugural Flowcytometry Workshop was held on 15 September at JCSMR . Approximately 30 enthusiastic participants from ANU, UC, CSIRO and The Canberra Hospital attended the lectures and laboratory exercises . The workshop was jointly organised by Microscopy and Cytometry Resource Facility staff at JCSMR and Becton Dickinson .
A*STAR A delegation of fourteen representatives from the Singapore Agency for Science and Technology Research (A*STAR) toured the JCSMR laboratories and facilities in Frank Gibson Laboratory, JCSMR June as part of their visit to The Australian Professor Frances Shannon and Mrs Robin Gibson unveil National University . the plaque at the naming ceremony for the Frank Gibson Laboratory . Professor Gibson took up the Chair of Biochemistry at JCSMR in 1967, which he held until his retirement in 1988 . He held the position of Director and Howard Florey Professor of Medical Research from 1977- 1980 . Many former colleagues and staff returned to the School for the opening ceremony .
Narrabundah College Visit Senior Biology students undertaking the International Australian Brain Bee Challenge Baccalaureate at Narrabundah College visited JCSMR Year 10 students from ACT High Schools participated in laboratories in March . The Membrane Physiology and the ACT Final of the Australian Brain Bee Challenge at Biophysics Group, the Gene Expression and Epigenomics JCSMR on Tuesday 16 June . Questions related to brain Group and the BRF guided these students through anatomy and physiology, with the students participating practical applications, providing them with a hands on in both individual and team competition rounds . experience of medical research .
112 The John Curtin School of Medical Research Annual Review 2009 Director’s Morning Tea The Director’s morning tea in Arawang Probus Club visit December was held to raise funds for the Salvation Army’s Christmas appeal .
Community contact 2009
National Youth Science Forum National Youth Science Forum students arrived in Canberra during January and four groups visited JCSMR . These students are from Year 11 and are planning careers in science, engineering and technology . The students were hosted by Dr Anneke Blackburn, Dr Nicole Beard, Associate Professor John Bekkers, Dr Kaori Ikeda, Dr Caryl Hill, Dr Dianne Webb, Professor Jill Gready and Mrs Anne Prins who introduced them to their research programs and facilities within the School .
World Day of Immunology JCSMR and The Australasian Society for Immunology celebrated World Day of Immunology on 29 April by inviting high school students from the ACT and around the surrounding region to attend a series of seminars in The Finkel Theatre . The first World Day of Immunology was held on 29 April 2005. It was brought to life by the European Federation of Immunological Societies in order to strengthen the public awareness of immunology as a basis for individual health and well-being.
St Francis Xavier College visit Laura Beaton, Honours student in the Humoral and Auto Immunity Group hosted a visit by St Francis Xavier College students, discussing her research and what it means to study at ANU .
Federal Members Visit JCSMR Federal Member for Canberra Annette Ellis MP and Federal Member for Fraser Bob McMullan MP visited JCSMR in July, following the delivery of $16 5. million of Federal funding for ANU towards Stage Three of the JCSMR redevelopment project .
The John Curtin School of Medical Research Annual Review 2009 113 Open day 2009
Every year, JCSMR holds an Open Day as part of the Australian Science Festival . • Open Day provides an opportunity for you to speak with working scientists in their laboratories .
On Open Day, the School is open to all members of the public.
We encourage all members of the general public, and students with an interest in medical research to visit JCSMR on Open Day.
Scientists carrying out research in fields such as cancer, diabetes, hearing, asthma and high blood pressure are available to answer your questions on Open Day.
114 The John Curtin School of Medical Research Annual Review 2009 Commitment to serving our community
Staff and students of the JCSMR are involved in many activities which extend beyond their laboratory work . JCSMR staff and students speak with community groups and interested members of the public through such activities as National Youth Science Forum and JCSMR Open Day, act as referees for many scientific publications and act as expert assessors for a wide range of national and international granting bodies . Some of the activities undertaken by JCSMR researchers are listed below .
Professor G .L . Ada Member: Australian Influenza Vaccine Committee Scientific Patron: Burnet Institute, Melbourne, VIC Dr N . Beard Presenter and Host: JCSMR Outreach Program, Canberra, ACT Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, ACT Associate Professor J .M . Bekkers Director: Australian Course in Advanced Neuroscience (ACAN), Moreton Bay Research Station, North Stradbroke Island, QLD Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, ACT Presenter and Host: JCSMR Outreach Program, Canberra, ACT Reviewing Editor: Frontiers in Neuroscience Reviewing Editor: BMC Neuroscience Member: Australian Neuroscience Society Member: Australian Physiological Society Member: Society for Neuroscience Dr E .M . Bertram Member: Australasian Society of Immunology Treasurer: Australasian Society of Immunology - ACT Branch Dr A . Blackburn Coordinator and Chair: Cancer Biology Workshop, JCSMR, Canberra, ACT Presenter and Host: JCSMR Outreach Program, Canberra, ACT Professor P .G . Board Member: ACT Gene Technology Advisory Council Member: International Society for the Study of Xenobiotics Council Editorial Board Member: The Open Drug Metabolism Journal Editorial Board Member: Drug Metabolism Reviews Editorial Board Member: The Sirraj Medical Journal Dr M .G . Casarotto Presenter and Host: JCSMR Outreach Program, Canberra, ACT Member: Biochemical Society (UK) Member: Australian and New Zealand Society for Magnetic Resonance Member: Protein Society Member: Australian Society for Medical Research (ASMR) Member: Australian Society for Biochemistry and Molecular Biology (ASBMB) Member: Australian Biophysics Society (ABS) Dr M . Cavazzini Presenter and Host: JCSMR Outreach Program, Canberra, ACT Participant and Demonstrator: ACT regional finals: Australian Brain Bee Challenge, JCSMR, Canberra, ACT
The John Curtin School of Medical Research Annual Review 2009 115 Dr G . Chaudhri National Coordinator: Australian Society of Immunology Celebration of World Day of Immunology Member: Australian Society of Immunology Member: Australian Society for Medical Research Member: International Society for Cytokine and Interferon Research
Dr J . Chen Chair: Canberra Society of Chinese Scholars Vice-President: Federation of Chinese Scholars in Australia
Dr M . Cook Presentation: Lupus Association Presentation: Immune Deficiency Foundation of Australia
Ms L .A . Coupland Conference Convener: Australian Vascular Biology Society 17th Annual Scientific Meeting, Canberra, ACT
Professor A .F . Dulhunty President: Australian Society for Biophysics Organiser: Curtin Conference on Ion Channels and Transporters, Canberra, ACT Member: Australian Physiological Society Member: USA Biophysical Society Editorial Board Member: Calcium Binding Proteins Editorial Board Member: Ion Channels Editorial Board Member: The Biochemical Journal Grant Assessor: ARC AusReader, NHMRC, European, USA and NZ Granting agencies
Professor S . Easteal Advisory Board Member: ARC Bioinformatics Centre of Excellence, University of Queensland, Brisbane, QLD Member: National Selection Committee, Australian-American Fulbright Commission Editorial Board Member: International Journal of Evolutionary Biology
Dr C . Freeman ACT representative: Matrix Biology Society of Australia and New Zealand Adviser for ACT cancer website: http://www .hotkey .net .au/~string/listing
Dr A . Garrett Member: Australian Neuroscience Society (ANS)
Professor C .C . Goodnow Member: Australian Academy of Science Special Elections Committee Medical Science Review Board Member: Juvenile Diabetes Research Foundation Member: Infection and Immunity Strategic Advisory Committee, The Wellcome Trust, UK Editorial Board Member: Immunity, The Journal of Experimental Medicine, Mammalian Genome, Journal of Autoimmunity, BMC Biology Communicating Editor: International Immunology
116 The John Curtin School of Medical Research Annual Review 2009 Service to our community 2009
Member: Australasian Society for Immunology Member: American Association for the Advancement of Science Member: American Association of Immunologists
Professor J .E . Gready Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, ACT Editorial Board Member: Bioinformatics and Biology Insights Initiator and Organising Committee Member: Workshop: Applying photosynthesis research to improvement of food crops, ANU, Canberra, ACT Fellow: Royal Australian Chemical Institute Member: Australian Society for Biochemistry and Molecular Biology Member: Australian Society for Medical Research Member: Australian Society for Biophysics
Dr R . Haddock ACT State Representative: Australian and New Zealand Microcirculation Society Member: National Association of Research Fellows Member: Australian Physiological Society Member: Australian Society for Clinical and Experimental Pharmacologists and Toxicologists
Professor C .E . Hill ACT Representative: ANZ Microcirculation Society Editor: Journal of Physiology (London) Editor: Journal of Vascular Research NHMRC Grant Review Panel Member Committee Member: Cardiovascular Special Interest Group, Australian Physiological and Pharmacological Society Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, ACT Presenter and Participant: JCSMR Open Day
Professor T . Hirst Editorial Board Member: International Journal of Medical Microbiology Editorial Board Adviser: Molecular Membrane Biology Board Director: Cryptopharma Pty Ltd Board Director: Warm Contact Pty Ltd Board Director: Dosimetry & Imaging Pty Ltd Board Director: Savine Therapeutics Pty Ltd Board Director: Synergetic Services Pty Ltd Board Director: Mylexa Pty Ltd
Dr G .F . Hoyne Councillor: Australian Society for Immunology - ACT Branch Coordinator: World Day of Immunology student workshop and Public Lecture, Canberra, ACT Co-organiser: Australian Society for Immunology Branch Meeting, ACT and NSW branches, Bowral, NSW Presenter and Host: JCSMR Outreach Program, Canberra, ACT
The John Curtin School of Medical Research Annual Review 2009 117 Dr G .A . Huttley Committee Member: High Throughput Sequence Steering Committee Committee Member: JCSMR Performance standards Member: IT/IS working party Committee Member: JCSMR Operations committee Editorial Board Member: The Open Genomics Journal, Biology Direct
Dr B . Kannappan Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, ACT
Associate Professor G . Karupiah Councillor: The Federation of Immunological Societies of Asia-Oceania Australian Delegate: International Union of Immunological Societies Member: Australasian Society for Immunology Member: Australian Society for Medical Research Member: American Society for Microbiology Member: American Society Virology Member: International Society for Cytokine and Interferon Research Member: Society for Natural Immunity
Dr M . Kole Instructor and presenter: Australian Course in Advanced Neuroscience (ACAN), Moreton Bay Research Station, North Stradbroke Island, QLD Co-Organiser: Kioloa Neuroscience Colloquium, Kioloa, NSW Member: Australian Neuroscience Society
Professor T .D . Lamb Chair: JCSMR External Relations Committee Member: JCSMR Executive Committee Research Director: ARC Centre of Excellence in Vision Science Editorial Board Member: Philosophical Transactions of the Royal Society B, Journal of General Physiology Finance Committee Member: Australian Academy of Science Member: Association for Research in Vision and Ophthalmology, Physiological Society Assessor: PhD Thesis, SISSA Italy
Professor J . Licinio Review Panel Member: US National Institute of Mental Health, National Institutes of Health, Interventions Committee for Adult Disorders (ITVA) Member: United States Department of Health and Human Services, Secretary Advisory Committee on Genetics, Health and Society Scientific Program Committee Chair: American Psychiatric Association Member, Membership and Scientific Program Committees: American College of Neuropsychopharmacology Member, Scientific Program Committee: American College of Psychiatrists Member, Communications Committee: Association for Clinical Research Training
118 The John Curtin School of Medical Research Annual Review 2009 Service to our community 2009
Founding President: International Society of Pharmacogenomics (ISP) Member: American Society of Human Genetics Member: Association for Patient-oriented Investigation Member: Collegium Internationale Neuro-Psychopharmacologicum (CINP) Member: Society for Neuroscience Member: The Endocrine Society Member: American Federation for Medical Research Member: Society of Biological Psychiatry
Professor K .I . Matthaei Deputy Chair: ANU Institutional Recombinant DNA Biosafety Committee Reviewer: Royan Institute International Research Awards Reviewer: National Health & Medical Research Council Reviewer: Australian Research Council Affiliate Member: Centre for the Molecular Genetics of Development Member: ARC Centre for Network in Genes and Environment in Development Participant: University of the Third Age (U3A) Ageing Forum Presenter and Host: JCSMR Outreach Program, Canberra, ACT
Dr P . Papathanasiou Presenter and participant: P & F Careers Forum for high school students at Canberra Grammar School, Canberra, ACT - “Biomedical Research”
Professor C .R . Parish Editor-in-Chief: Immunology and Cell Biology Medical Research Advisory Committee Member: The Australian Cancer Research Foundation Council Member: The International Union of Immunological Societies (IUIS) Organising Committee Chair: 17th Annual Scientific Meeting, Australian Vascular Biology Society, Canberra, ACT Revision Consultant: AllergoOncology Abstracts, XXI World Allergy Congress, Buenos Aires, Argentina
Dr G . Paz-Filho Reviewer: Grant application to The French National Institute of Health and Medical Research (INSERM) 2010 Call for Proposals in Translational Clinical Research
Ms A . Prins Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, ACT Presenter and Host: JCSMR Outreach Program, Canberra, ACT Presenter and Participant: JCSMR Open Day Coordinator and Instructor: Surgical Cut Up Workshop: Upskilling Histological technique and practice for current practicing histologists
The John Curtin School of Medical Research Annual Review 2009 119 Professor I .A . Ramshaw Scientific Advisory Panel Member: Westmead Institute for Cancer Research Editorial Board Member: Viral Immunology Editorial Board Member: Microbes and Infection
Dr C . Ranasinghe Volunteer Assistant: Holy Family Care Centre for HIV/AIDS orphans, Ofcolaco, Limpopo, South Africa Presenter: Forum for high school students, HIV/AIDS can we find a vaccine?, Canberra Girl's Grammar School, Canberra, ACT ACT Representative: Mucosal Immunology special interest group Member: Australasian Society for Immunology Member: Society for Mucosal Immunology
Dr D . Rangasamy Executive Editor: Biotechnology Letters Member: ANU Human Research Ethics committee
Dr C .R . Raymond ACT Council Representative: Australian Neuroscience Society Master of Ceremonies ACT regional finals: Australian Brain Bee Challenge, JCSMR, Canberra, ACT Co-Organiser: Kioloa Neuroscience Colloquium, Kioloa, NSW Deputy Director: Australian Course in Advanced Neuroscience (ACAN), Moreton Bay Research Station, North Stradbroke Island, QLD Local Organising Committee Member: The 29th Annual Meeting of the Australian Neuroscience Society, 2009 Reviewing Editor: Frontiers in Cellular Neuroscience
Dr R . Rigby Participant: CSIRO “Scientists in Schools” program
Professor M .F . Shannon Editorial Board member: FEBS Letters (The Journal of the Federation of European Biochemical Societies) Management Committee Member: Centre for Vascular Research, The University of New South Wales, Sydney, NSW President: Lorne Genome Inc ACT Council Representative: Australian Society for Biochemistry and Molecular Biology
Associate Professor C . Stricker Instructor and presenter: Australian Course in Advanced Neuroscience (ACAN), Moreton Bay Research Station, North Stradbroke Island, QLD
Professor G .J . Stuart Instructor and presenter: Australian Course in Advanced Neuroscience (ACAN), Moreton Bay Research Station, North Stradbroke Island, QLD Associate Editor: Frontiers in Cellular Neuroscience
120 The John Curtin School of Medical Research Annual Review 2009 Service to our community 2009
Chair: Gordon Research Conference, Lucca (Barga), Italy Member: Local organisation committee for the 2009 Australian Neuroscience Society meeting, Canberra, Australia . Research Committee Member: Motoneuron Disease Research Institute of Australia Member: Sydney Chapter of the American Society of Neuroscience Council
Dr M .L . Tierney Instructor and presenter: Australian Course in Advanced Neuroscience (ACAN), Moreton Bay Research Station, North Stradbroke Island, QLD Scientific Member: ANU Animal Experimentation Ethics Committee (AEEC) Organising Committee Member: 2010 Curtin/Gage Conference - Ion Channels and Transporters, Canberra, ACT Presenter and Host: JCSMR Outreach Program, Canberra, ACT
Professor D J. . Tremethick Committee member: ACT branch of Australian Society for Medical Research ACT representative: The Australian Society of Biochemistry and Molecular Biology Editorial Board Member: Chromosome Research, Epigenetics, Chemtracts for Biochemistry and Molecular Biology Member: Lorne Genome society Member: Australian Society for Biochemistry & Molecular Biology Member: American Society for Microbiology
Dr C .G . Vinuesa Member: EC Scientific Advisory Council: SYBILLA European Community Program Editor: News & Commentary, Immunology and Cell Biology Permanent Member: ANU Animal Experimentation Ethics Committee (AEEC) Member: Australasian Society for Immunology Member: American Association of Immunologists
Professor B . Walmsley Presenter and Host: JCSMR Outreach Program, Canberra, ACT Participant: University of the Third Age (U3A) Ageing Forum Presenter and Participant: JCSMR Open Day
Associate Professor H .S . Warren Editorial Board Member: Immunology and Cell Biology
Dr D .C . Webb Presenter and Host: JCSMR Outreach Program, Canberra, ACT Participant: ACT and NSW Asthma Foundations- Promotion of Asthma Awareness and Research Presenter and Participant: National Youth Science Forum, JCSMR, ANU, Canberra, ACT
Professor J .A . Whitworth Patron: TADACT, Technical Aid to the Disabled, Canberra, ACT (until November) Patron: Wesley Institute, QLD
The John Curtin School of Medical Research Annual Review 2009 121 Service to our community 2009
Trustee: High Blood Pressure Research Council of Australia Board Member: Menzies Research Institute, Hobart, TAS Co-Chair: NSW Health Care Advisory Council Chair: Global Advisory Committee on Health Research, WHO Member: WHO Expert Advisory Panel on Health Science and Technology Policy
Dr R . Williams Member: Organising Committee, Australasian Microarray and Associated Technologies (AMATA) Meeting, Katoomba, NSW Member: Organising Committee, 57th Genetics Society of Australasia Conference, Brisbane, QLD Session Organiser and Chair: ComBio, Christchurch, NZ External Reviewer: National Health and Medical Research Council of Australia PhD thesis Examiner: University of Sydney, Sydney, NSW Presenter and Participant: JCSMR Open Day
Professor M-L . Wong Associate Editor: Molecular Psychiatry Reviewer: Pharmacogenomics Special Emphasis Panel for applications in response to the RFA Pharmacogenomics Research Network, National Institute of General Medical Sciences (NIGMS/NIH), US
Professor I .G . Young Awards Committee Member: Australian Society for Biochemistry and Molecular Biology Assessor: Chinese University of Hong Kong
Dr Y . Zhang Presenter and Participant: JCSMR Open Day
122 The John Curtin School of Medical Research Annual Review 2009 Support to the School 2009
• Grants • Statistics • Donors
The John Curtin School of Medical Research Annual Review 2009 Grants 2009
Australian Capital Territory Health and Professor C.R. Parish, Dr J . Altin, Professor P.G. Medical Research Council Large Project Board, Dr M. Cassarotto, Dr M . Djordjevic, Professor Development Grant A. Dulhunty, Professor C . Easton, Professor C.E. Hill, Professor K.I. Matthaei, Professor G . Otting and Professor I.A. Ramshaw Dr M.L. Tierney The Development of a Cross-strain and Cross- Microwave Assisted Peptide Synthesiser subtype Pre Pandemic Influenza Vaccine using Savine $115,000 Technology $156,250 Professor C.G. Vinuesa, Professor C.C. Goodnow, Professor C. Parish, Associate Professor G. Australian Institute of Sport General and Karupiah, Professor H . O’Neill, Dr S. Rao, Dr G. Collaborative Grants Hoyne, Dr K. Hardy, Dr M.C. Cook, Dr A . Fahrer and Dr P. Pouliquin Dr J .A . Hawley, Dr J. Henderson, Dr R.B.H. Williams, High Performance/high throughput fluorescence and Professor S. Easteal activated cell sorter What is the predictive utility of exercise-induced gene $320,000 expression in blood and muscle? $20,000 Australian Research Council Centre of ANU Major Equipment Committee Awards Excellence for Integrative Legume Research Professor P . Gresshoff, Professor C . Beveridge, Dr B . Dr G . Allison, Professor M . Spriggs, Dr A. Blackburn, Carroll, Professor B . Rolfe, Professor C.R. Parish, Dr Dr B .J K. . Evans, Dr R . Arkell, Dr M. Cook, Professor S. M . Djordjevic, Dr G . Weiller, Dr U . Mathesius, Dr R . Easteal, Professor W . Foley, Dr J .S . Keogh, Professor Rose, Professor M . Singh and Dr P . Bhalla J . Graves, Dr G.F. Hoyne, Dr G.A. Huttley, Professor $100,000 S . Broer, Dr J . Cavanaugh, Dr A . Millar, Dr S. Rao, Professor R . Saint, Dr R. Williams, Professor M.F. Shannon, Professor M . Badger, Dr C . Cazzonelli, Australian Research Council Centre Professor C.C. Goodnow, Dr D . Gordon, Professor R . of Excellence in Vision Science (in Peakall, Dr B . Pogson, Dr E . Ball, Dr S . Bedford, Dr C . partnership with University of QLD, Behm, Dr M . Djordjevic, Dr C.G. Vinuesa, Professor University of Sydney, University of J.E. Gready, Dr D . Hayward, Dr I . Nijat, Dr U . Western Australia) Mathesius, Professor C.R. Parish, Dr D. Rangasamy, Professor T.D. Lamb, Dr S . Cringle, Professor B . Professor B .G . Rolfe, Professor D.J. Tremethick, Dr G . Dreher, Professor M . Edwards, Dr M .R . Ibbotson, Dr A . Weiller, Dr G . Collins, Professor E . Dennis, Dr D . Lovell, James, Dr T . Maddess, Professor I . Morgan, Professor Dr T . Agostino, Dr G . Kennedy and Dr A . Young J . Provis, Professor M .V . Srinivasan, Professor J . Stone, Next generation high throughput DNA sequencer Dr K . Valter, Professor D I. . Vaney, Professor D .-Y . Yu, $175,000 Professor J . Zeil, Dr S . Zhang Professor C.R. Parish, Professor P.G. Board, $2,381,932 Professor K.I. Matthaei, Professor A.F. Dulhunty, Dr M. Hulett, Professor D.J. Tremethick, Professor C.E. Australian Research Council Discovery Hill, Dr D. Rangasamy, Dr M.G. Casarotto, Dr C.J. Grants Simeonovic, Dr J. Altin and Dr R. Li Professor P.G. Board Confocal Microscope System The role of gamma glutamyl cyclotransferase in $482,000 glutathione homeostasis $45,000 Professor A.F. Dulhunty and Professor R . Dirksen Structural determinants of an intracellular calcium store $80,000
124 The John Curtin School of Medical Research Annual Review 20082009 Grants 2009
Professor J.E. Gready and Dr P.L. Cummins Dr D . Talaulikar and Associate Professor H.S. Warren Importance of conformational and electrostatic Lymphocyte populations in diffuse large B-cell (and contributions in simulations of enzyme reaction other aggressive) Non-Hodgkins’s lymphoma mechanisms $28,882 $90,136 Professor D.J. Tremethick Commonwealth Department of Health The dynamic control of chromatin structure and Ageing Anti-Doping Research $85,000 Program Professor S. Easteal, Dr M . Ashenden, Dr C . Gore, Dr Australian Research Council Federation R.B.H. Williams and Dr J. Henderson, Fellowship Novel high throughput c-DNA sequencing (RNA-seq) Professor C.C. Goodnow to identify a genomic signature for autologous blood Discovering genes and mechanisms regulating transfusion immune responses $146,329 $316,222 Commonwealth Department of Australian Research Council Linkage Innovation Industry Science and Grant: Infrastructure Equipment Facilities Research (DIISR) International Science Dr G . Allison, Professor A . Hardham, Professor M.F. Linkages Program Shannon, Professor M . Badger, Dr C . Cazzonelli, Dr D . Professor C.C. Goodnow, Dr E. Bertram, Mr G. McNevin and Dr E . Dennis Sjollema, Dr S. Winslade, Professor P . Doherty, A massively parallel genome analysis facility for the Professor D .J . Hilton, Professor S . Turner, Dr P . ACT region Hertzog, Dr H . Tang, Dr G . Gao and Dr S . Wang $550,000 Genetically resistant mouse strains of avian influenza $475,000 Bioplatforms Australia Ltd/National Collaborative Research Infrastructure Commonwealth Department of Strategy in conjunction with ANU and Innovation Industry Science and CSIRO Research (DIISR) National Collaborative Professor M.F. Shannon and Dr E . Dennis Research Infrastructure Strategy Epigenomics node of Genomics Australia – Dr S. Winslade Bioplatforms Australia Implementing the Australian Phenomics Network for $262,000 the National Collaborative Research Infrastructure Strategy’s Research Capability known as ‘Integrated The Canberra Hospital Private Practice Fund Biological Systems’ Dr M. Cook $1,146,904 Investigation of phenotype and genotype of primary immune deficiency disease Grains Research and $60,000 Development Corporation Professor P . Gatenby, Dr P Smith, Dr R Li, Dr C Professor J.E. Gready Freeman and Dr J . Scarvell Identifying wheat germplasm with superior Rubiscos Heparanase may be a potential biomarker of disease for breeding for increased drought tolerance activity in Rheumatoid Arthritis $150,035 $50,000
The John Curtin School of Medical Research Annual Review 20082009 125 Juvenile Diabetes Research Foundation Translating population-based mental health and Professor C.C. Goodnow and Dr S. Daley ageing research into evidence-based prevention Antibody-enhanced antigen presentation for CD4 cell and policy tolerance of islets $354,050 $180,000 Dr C.G. Vinuesa National Health & Medical Research Roquin prevents autoimmune diabetes through a Council Development Grant novel tolerance pathway Associate Professor H.S. Warren $51,710 NK cells and monoclonal antibody therapy in lymphoma patients The Menzies Foundation $50,000 Professor S . Leeder, Mr R . Wells and Professor J.A. Whitworth National Health & Medical Research The Menzies Centre for Health Policy Council Enabling Grant $62,000 Professor C.C. Goodnow Australian Phenome Bank Sir Robert Menzies Memorial Foundation $225,000 Menzies Research Centre Grant Dr A. Liston National Health & Medical Research RG Menzies Fellowship Council Program Grants $5,000 Professor C . MacKay, Professor J . Sprent, Professor C.C. Goodnow, Dr F . MacKay, Dr C.G. Vinuesa, National Breast Cancer Foundation of Professor A . Basten, Professor B . Fazekas de St Groth, Dr S . Tangye and Dr R . Brink Australia Novel Concept Award Molecular and cellular studies of the adaptive Dr A.C. Blackburn and Professor P.G. Board immune response in health and disease Chemoprevention of breast cancer with a $707,000 nonhormonal, non-toxic anticancer agent Dr M . Berndt, Professor C . Chesterman, Professor $90,046 B . Chong, Professor P . Hogg, Associate Professor L . Khachigian, Professor C.R. Parish and Dr R . Stocker National Health & Medical Research Vascular biology Council CJ Martin Fellowship $486,123 Dr A. Cook The role of the histone NSAP in regulating histone National Health & Medical Research dynamics Council Project Grants $115,013 Dr N.A. Beard Mr A. Sutherland Identification of cardiac sarcoplasmic reticulum: Mechanisms of metabolic and immunological Targets for cardiotoxic drugs regulation by the novel transcription factor DPZF $88,500 $68,500 Associate Professor J.M. Bekkers Synaptic inhibition and the control of excitability in National Health & Medical Research the rodent piriform cortex Council Capacity Building Grant in $147,000 Population Health Research Professor P.G. Board Professor H . Christensen, Dr K . Anstey, Dr P . The evaluation of gamma-gluamylcyclotransferase as Butterworth, Professor S. Easteal, Dr K . Griffiths and a novel target for cancer therapy and diagnosis Professor A . Mackinnon $138,875
126 The John Curtin School of Medical Research Annual Review 20082009 Grants 2009
Professor P.G. Board, Professor A.F. Dulhunty and Dr M.D. Hulett Dr M.G. Casarotto The function of histidine-rich glycoprotein in Communication between calcium ion channels in inflammation and cancer skeletal muscle excitation-contraction coupling $144,000 $192,938 Dr M.D. Hulett and Professor K.I. Matthaei Professor P.G. Board, Professor A.F. Dulhunty and Dissecting the function of heparanase in inflammatory Dr M.G. Casarotto disease using genetic tissue-specific ablation Glutathione transferase-derived compounds as $185,916 therapeutic agents Dr M. Kole $133,875 Identification and function of Kv7/M-channels in Professor P.G. Board, Professor K.I. Matthaei, Dr A. axons of cortical neurons Blackburn, Dr A. Shield, and Dr J . Dahlstrom $107,500 Glutathione transferase deficient mice to probe for Dr A . Kromykh and Dr M. Lobigs adverse drug reactions Viral factors involved in flavivirus replication and $180,500 virus-host interactions Dr G. Chaudri and Associate Professor G. Karupiah $72,250 Regulation of antiviral and anti-inflammatory Professor C.R. Parish and Dr B. Quah responses by mTNF: Key role of reverse signalling by Antigen receptor sharing by lymphocytes during an host and viral TNFR immune response $183,500 $91,750 Dr M . McGuckin, Dr T . Florin, Dr G . Radford-Smith, Dr Dr C. Ranasinghe R . Eri and Dr M.C. Cook Enhancement of mucosal immunity and CTL avidity Goblet cell stress and intestinal inflammation against HIV-1 $584,250 $180,500 Dr K . Anstey, Professor H . Christensen, Professor A . Dr S. Rao Mackinnon, Dr P . Butterworth and Professor S. Easteal Transcriptional regulation and the role of key histone A longitudinal study of depression, anxiety, substance variants in defining gene-specific chromatin states use and cognitive change: PATH Through Life Wave 3 $147,800 $544,200 Dr S . Turner, Dr S. Rao, Professor D.J. Tremethick Professor P .S . Foster, Professor R K. . Kumar, Professor and Dr T. Juelich K.I. Matthaei, Associate Professor J . Mattes Chromatin remodeling and transcriptional regulation The role of microRNA as a target for a novel of CD8 T-cell effector gene expression treatment of Asthma $90,725 $200,125 Dr C.R. Raymond Professor C.E. Hill and Dr S . Sandow The role of action potentials in local calcium Voltage dependent calcium channels and vascular signalling and induction of different forms of LTP function: Do microdomains determine function? $104,250 $183,500 Professor M.F. Shannon Professor C.E. Hill and Professor K.I. Matthaei The role of c-Rel in controlling chromatin architecture The role of connexins in blood pressure regulation: and transcription networks in T lymphocytes Use of a conditional gene expression system $170,500 $196,625 Professor M.F. Shannon, Dr K. Hardy and Dr A . Professor T. Hirst Holloway Cholera toxin co-receptor interaction in the Epigenomic marks as indicators of the kinetics of prevention of inflammatory autoimmune disorders gene expression in immune cells $115,875 $188,500
The John Curtin School of Medical Research Annual Review 20082009 127 Dr S . Barry, Professor M.F. Shannon, Professor H . Professor I.G. Young and Professor P .S . Foster Zola and Professor R . D’Andrea Role of IL-3 in allergic inflammation: modulation of Functional validation of FoxP3 targets genes in basophils mast cells eosinophils and remodelling human regulatory T cells in asthma $25,000 $158,500 Dr S . Gerondakis and Professor M.F. Shannon Dr Y. Zhang and Professor J.A. Whitworth The transcription factors c-Rel and Rel! serve distinct Nitroso-redox imbalance in glucocorticoid-induced roles in the development and function of CD4 hypertension regulatory T cells $109,250 $64,750 Professor G.J. Stuart National Health & Medical Research Cellular mechanisms underlying absence epilepsy Council R .D . Wright Biomedical Career $93,750 Development Awards Professor G.J. Stuart Dr A. Blackburn Investigating action potential initiation and $87,250 propagation in neurons using voltage-sensitive dyes Dr D. Rangasamy $101,500 $90,500 Professor G.J. Stuart and Dr J-D. Breton Brain plasticity following changes in sensory input National Health & Medical Research $100,000 Council Research Fellowship Dr M.L. Tierney Dr P. Papathanasiou Structural determinants underlying high conductance An investigation of reprogramming and lineage GABA–A channels switching/selection in somatic mouse stem cells $110,000 through the manipulation of critical nuclear Professor D.J. Tremethick regulatory factors Regulation of the histone code by histone variants $17,125 $188,500 Professor D.J. Tremethick National Health & Medical Research The organisation of the chromosome into distinct Council Senior Research Fellowships epigenetic domains and its link with development and Associate Professor G. Karupiah disease $119,000 $168,750 Dr C.G Vinuesa, Dr M.C. Cook, Professor C.C. National Health & Medical Research Goodnow, Dr G.A. Huttley and Associate Professor N . Council Special Program in Diabetes Manolios Professor C.R. Parish, Dr G.F. Hoyne, Dr C. Freeman Genetic pathology of Roquin in human autoimmune and Dr C.J. Simeonovic disease Role of heparan sulfate heparanase and heparanase $158,500 inhibitors in the development and prevention of Professor B. Walmsley Type I Diabetes Plasticity in central auditory pathways $600,000 $90,750 National Health & Medical Research Dr D.C. Webb and Professor P.G. Board The role of glutathione transferase P1 in regulating Council Training (Postgraduate) Awards allergic airways disease Dr E. Amyes $139,750 Enhancing and Evaluating T Cell Responses to Candidate HIV Prime-Boost Vaccines $67,250
128 The John Curtin School of Medical Research Annual Review 20082009 Grants 2009
Dr J. Ellyard Ramaciotti Foundation Major Research The effect of follicular helper T cells on AID regulation Award and selection of high affinity germinal centre B cells Professor C.C. Goodnow and Dr A. Enders $105,181 Ramaciotti Immunization Genomics Laboratory Dr R. Haddock $200,000 Obesity and Diabetes: Understanding cardiovascular risk factors and identification of novel Roche Organ Transplantation Research targets for treatment Foundation / Juvenile Diabetes Research $36,625 Foundation (Switzerland) Dr A. Liston Dr C.J. Simeonovic, Professor C.R. Parish, Dr C. Genetic Characterisation of Factors Affecting Freeman, Ms S. Popp and Ms D. Brown Generation of Foxp3+ Regulatory T Cells Roles of heparanase and its inhibitor PI-88 in the $67,250 immune destruction and protection of islet grafts $30,000 Dr B. Quah Intercellular communication of antigen receptors during immune response development Vaxine Pty Ltd Dr M. Lobigs $67,250 Flavivirus vaccines based on inulin adjuvants Dr L. Tze $12,500 Genetic Characterisation of Factors Involved in Regulating the Production of Autoantibodies Sylvia and Charles Viertel Senior Medical $67,250 Research Fellowship Dr C.G. Vinuesa National Institute of Allergy and The Roquin tolerance pathway: biology, pathology, Infectious Disease, National Institutes of and therapeutic strategies Health, US $195,000 Professor R . Ulevitch, Dr A . Aderem, Dr B . Beutler, Professor L . Teyton, Professor C.C. Goodnow, Dr The Wellcome Trust Strategic Programme G . Nolan, Dr E. Bertram, Dr D . Tscharke, Associate Grant and Dr I . Schmulevitch Professor G. Karupiah Professor R .J . Cornall, Professor J .I . Bell, Professor C.C. Systems approach to immunity and inflammation Goodnow, Dr M . Lathrop, Professor W . Britton and Dr $1,100,984 C.G. Vinuesa Immunity and Infection Genomics Consortium National Institutes of Health (US) $797,911 Program Grant Dr D. Tscharke and Associate Professor G. Karupiah World Anti-Doping Authority CD8+ T cell specificity in mouse models of small pox Dr M .J . Ashenden, Professor S, Easteal, Dr R.B.H. vaccination and challenge Williams and Dr J. Henderson $103,939 Confirmation of differentially expressed genes associated with autologous transfusion . National Institutes of Health (US) $64,000 Project Grants Professor A.F. Dulhunty and Professor R . Dirksen Control of calcium movements in muscle $19,278 (in conjunction with The University of Rochester, NY, US)
The John Curtin School of Medical Research Annual Review 20082009 129 Statistics 2009
Staff Numbers 2009 2008 2007 Academic staff 91 93 92 General Staff — administration, technical & support 114 110 203 Graduate students 85 69 81
Income Base Allocation $14,480,000 Special Purpose Funds (SPF) $12,082,000 IGS, RTS, RIBG $3,403,000 Other Income $4,917,000 Adjustments -$1,895,000 TOTAL INCOME $32,997,000
Expenditure Staff Costs $9,365,000 Special Purpose Funds (SPF) $12,082,000 Other $3,170,000 Expendable Research Material (ERM) $2,714,000 Scholarships $768,000 Equipment $1,914,000 Travel $465,000 Transfers to Other (ABS) $3,012,000 TOTAL EXPENDITURE $33,490,000
Special Purpose Funds Government Grants $8,820,000 Other $3,262,000 TOTAL $12,082,000
130 The John Curtin School of Medical Research Annual Review 20082009 Donors 2009
The Director, staff and students of JCSMR are extremely grateful for the continued generosity of our friends and donors .
We would like to thank the following donors for their generous support in 2009
Professor Gordon Ada Family and Friends of Professor Frank Gibson Mrs Vera Bailey Hughes Baptist Church U3A Group Mr Gordon and Mrs Gretel Bootes Ms Noeleen M. Jeffery Ms Evelyn Bugna Mr Michael Kneebone Mr Phil and Mrs Sue Bunyan Mr B. and Mrs J. Le Mesurier Mr Richard I. Christopherson Mr Lou and Mrs Mavis Martignago P. Clarke Mr John B. McLean M.J. Cockburn Ms Heather McLoughlin Mr P.A. and Mrs N. Deasey Mr John Milne Department of Defence Professor Robert K. Poole Mr Lennard W. Dyer Mr Tony Puglisi Mr Bert and Mrs Maureen Finney Ms Christine E. Purdon Mrs Yvonne Finney Mr Robert P. Routh Family and Friends of Mr Keith Finney Mr Owen E. Ryan
Professor Frank Fenner Mr Robert M. Tupper
Dr Joyce Fildes Mr R.J. and Mrs M.L. Williams
Dr Alan and Dr Elizabeth Finkel Dr Gwen Woodroofe
Professor Joe Gani The Zonta Breakfast Club of Canberra
The John Curtin School of Medical Research Annual Review 20082009 131 The John Curtin School of Medical Research needs your support
Gifts and bequests to the School are used to fund vital research projects in areas such as asthma, cancer, diabetes, hearing loss and vision, as well as providing scholarships and purchasing specialised equipment. Your support can be provided in a number of ways including a gift or bequest that may assist in funding a particular area of research, or a scholarship or prize.
If you would like to discuss options for supporting JCSMR, please contact:
Dr Madeleine Nicol T: +61 2 6125 2577 F: +61 2 6125 2337 M: 0407 278 913 E: [email protected]
132 The John Curtin School of Medical Research Annual Review 2009