THE NEWSLETTER OF ST VINCENT’S INSTITUTE OF MEDICAL RESEARCH/DECEMBER 2008

THE

UNRAVELLING LEUKAEMIA

BlackRock Investment Management (Australia) Limited Proudly sponsoring the SVI December Newsletter EgdjYanhedchdg^c\i]ZHK>6j\jhiCZlhaZiiZg the grant and help from our grants offi cer, Dr Anne Johnston. NEW Missing out on grants is a major problem for our scientists – a time when they need the er THERAPY

Institute’s support. The way i grants are awarded it is very diffi cult to build up a “rainy-day” HOPE fund therefore much rides on whether grants are successful. New therapies for The support of the community - leukaemia are under your support - is also vital to our development at SVI scientists. Even when successful following the discovery of Tom in obtaining a competitive grant, the structure of a protein this is usually not suffi cient to responsible for the fully fund the work being done. production of It is especially common for malfunctioning blood cells. says essential items of equipment not SVI’s Michael Parker and to be funded at all. Applications his collaborators discovered to Trusts and Foundations and the structure of a molecule funds donated by individuals are involved in leukaemia

Our NHMRC Project Grant Front The essential ways that important and certain infl ammatory results get top billing in this work can be done. There are diseases such as rheumatoid newsletter. It seems like also shortfalls in funding the arthritis and asthma. tempting fate and makes me “indirect” cost of research reach out to “touch wood” Work has already such as building operations, – a desperate measure for a commenced to fi nd maintenance and administration. researcher – to talk about them antibodies to block its action These are funded by Government too much. We had a very high holding great promise for infrastructure grants. Again success rate and congratulations new treatments. there is a funding “gap” here to all those who were funded. It is The announcement of which we support from Institute just so exciting for our scientists this latest discovery from funds. to receive a “thumbs-up” from Michael Parker’s Structural this extremely competitive Therefore, a vital part of SVI’s Biology Unit was reported system. Of course it is also a success is to be able to purchase around the world in August. diffi cult time for those who were equipment and facilitate our Following years of unsuccessful and this happens staff’s research at crucial career painstaking research by at times to the best of scientists. stages. Your support is essential. two groups of scientists The NHMRC will never be We are very aware of the tough based at SVI and the Hanson able to fund all the worthwhile economic conditions that will Institute, Adelaide, the applications it receives. make for trying times over the discovery was published in Applying to a scheme that funds coming year. These are sure to the prestigious journal, Cell. create problems for all of us. SVI on average about a quarter The research focuses on the is in a sound fi nancial position of the grants submitted for a receptor of a hormone called but we are obviously very three-year period and then is GM-CSF which transmits highly competitive again to get dependent on continued support messages into white blood renewed support is daunting for for medical research from the cells to direct them to all scientists. There is no doubt Federal and State Governments reproduce. that the diffi culties of doing this and from the community. Professor Tom Kay, SVI Director Abnormalities in this cell dissuade many from a career in Thank you for your support signaling process cause science even when they may in 2008 – We look forward to the over-production of have much to offer. staying in touch with you and cells, the production of We do our best to help people hope you will be able to continue malfunctioning cells, or prepare grants prior to your support in 2009. Have a very allows cells to persist for too submission through the efforts of enjoyable Christmas and holiday long, causing diseases such experienced colleagues reading season. as leukaemia. Using synchrotron and its structure is such that Photo: Professor technology the structure of antibodies are the therapy of Michael Parker, the receptor bound to its choice which is a relatively who led the hormone was established SVI team in the straight-forward technology discovery of the and Michael Parker’s group leading to a faster result.” GM-CSF receptor developed a 3D virtual structure “It should be stressed that, image for use in the next stage of research. as for any drug development program, there are no In partnership with guarantees of success and pharmaceutical company a number of hurdles are CSL, researchers will use still to be overcome as the knowledge of the receptor’s structure to fi nd potential development proceeds.” DRUG drug compounds that could “However, if we can stop block its action. the signal for uncontrolled discovery Michael Parker said: growth of the cells, we can “Normally drug design is stop the development of Our body is made of proteins 15 years from start to fi nish certain leukaemias,” he which control the body’s but the nature of this protein continued. functions. Determining the structure of a protein can help us to understand its function and “ its role in disease. If we can Unravelling the Traditionally, drugs to treat a stop the specifi c disease causing protein leukaemia link signal for were identifi ed through a painstaking process of trial and The GM-CSF hormone controls the production of blood cells and is uncontrol- error. sent by the body to give the signal for more blood cell production if, led growth The modern, or rational for example, more white blood cells are required. approach involves identifying of the cells, the 3-D structure of the protein we can involved in disease and then The GM-CSF hormone (purple) designing a drug to block or binds to the receptor which stop the promote its action. consists of two chains (red and develop- SVI houses the ACRF Rational blue) on the cell surface. ment of Drug Discovery Facility, led by Professor Michael Parker, which certain allows researchers to visualise St Vincent’s Institute and Hanson Institute scientists have leukaemias the 3-D structure of proteins discovered the structure of the GM-CSF receptor bound to the involved in disease. hormone for the fi rst time and have created a computerised 3D The atomic structures are model to visualise it. defi ned by shooting X-rays The binding process happens at crystals of the protein to several times,creating a chain of generate X-ray scattering bound receptors leading to signals patterns that can be converted being generated and sent into ” into 3D images. the cell. This knowledge provides fundamental information about Abnormal receptor signaling causes the over-production of cells, the architecture of a protein the production of malfunctioning cells or cells that persist too long, including its active site, which resulting in diseases such as leukaemia. can be targeted for drug design. Over the past thirty years ANTIBODY DRUG SVI has solved more protein structures than all other The next stage is to fi nd drug Front cover and crystallography units in illustration by Jack compounds that will block the King-Scott, SVI Australia and is currently abnormal GM-CSF receptor working on therapies for cancer, signaling. Alzheimer’s, asthma, rheumatoid arthritis, infection, neurobiology and leukaemia. Pancreatic islet cells

from donor to recipient

Tom Loudovaris - have progressive secondary isolation process, taking breaks has been working complications despite is diffi cult, the perseverance and in the St Vincent’s adherence to their insulin dedication of our team members Islet Transplant regimen. is to be commended. Program for four Although islet transplantation as How successful has the years, managing currently practiced has program been? the team that limitations and will not Each recipient usually requires isolates the insulin signifi cantly relieve the burden of two transplants. Our fi rst producing islet cells from the type 1 diabetes in the recipient has had two transplants donor pancreas prior to community, it will provide a and no longer requires insulin “ transplantation. platform to trial future insulin- injections. Two other patients The best Part of the dedicated team who producing cell therapies that will have had their fi rst transplant ensured the success of the fi rst be more widely applicable. and their requirement for part of the Victorian Islet Transplant in What do you need to match injected insulin has reduced to December 2007, here Tom gives when seeking a donor less than half. We have two more job is ... us an insight into the isolation pancreas? recipients who are waiting for process that makes this We don’t age or gender match their fi rst transplant. transform- treatment possible for people but we do match for blood type. What are the long-term with a severe form of type 1 What happens when you get results? ing the diabetes. word that a matching On average, patients who lives of our What is the best part of your pancreas is available? respond well to islet job? I get an offer of a pancreas from transplantation report being free transplant The best part of the job is that it the organ donor coordinators, of the need for insulin for at least is a team effort. I work with a usually in the middle of the night. a year, with some islets still wonderful group of people, who Once I accept, VTIS is notifi ed functioning after 7 years. This is recipients share a similar passion and and tissue matching with our similar to the rate of insulin whose involvement makes the recipients occurs. The results are independence achieved and their islet transplant program happen faxed in two to three hours and following whole pancreas and the ultimate result – we then make the decision to go transplantation. Although only a families transforming the lives of our ahead. small percentage of islet transplant recipients and their Once surgical retrieval of the transplant patients are insulin families. donor’s pancreas has occurred, independent long term, the What are the criteria for we organise collection. The control of blood sugar levels is needing an islet transplant? isolation of the insulin-producing greatly improved in most patients. Those needing a transplant are cells or islets occurs in a adults aged 18-65 with unstable cleanroom at the Peter Do you carry out research on unused islets? ” type 1 diabetes who: MacCallum Cancer Centre and takes six to eight hours with a Occasionally, we do not get - have lived with type 1 diabetes team of four people. More time in transplantable quantities of islets for a period of at least 5 years the cleanroom is required the from donors and some donors are - have unstable blood glucose next day if we go on to unsuitable for transplant. If levels including severe and transplant. research consent is given by the frequent hypoglycaemic With the use of sterile protective donor family, we use these islets episodes that cause a major gowning, arduous entry and exit in our research to fi nd ways to disruption in lifestyle procedures and the intensive make the clinical outcome better. SVI’s Carl Walkley recently research is directed to creating made a leap forward in the ‘mouse models’ of human study of osteosarcoma, the most diseases by altering the genes common primary cancer of bone responsible for a particular through the development of a disease. new research model. In collaboration with former It is diffi cult to study the colleagues at the Dana-Farber “ progression of serious diseases, Cancer Institute at Harvard, Carl develop- such as cancer, in humans. is developing a mouse model of ing the However, the introduction of osteosarcoma. The model will be transgenic mice in 1982 used as a means to test new model as a Carl’s transformed modern medical therapies that could prevent the means to research making it possible to initiation and spread of this replicate, study and fi nd devastating cancer. test new cancer solutions to human diseases Carl is working with Natalie therapies inside the laboratory. Sims and Jack Martin in SVI’s The DNA of mice is very similar Bone & Cancer Unit to further that could study to that of humans and much this research. prevent the initia- tion and spread of this dev- astating cancer Greg on obesity increased risk of heart failure ” At SVI’s Obesity Seminar who could benefi t from JOCK’S held in October, Greg preventive treatments. Steinberg gave his audience To study the mechanisms of an insight into his research heart heart failure, he has collaborated into obesity, type 2 diabetes with cardiologists and surgeons and the benefi cial effects of at St. Vincent’s Health to exercise. insights establish a cardiac tissue bank. With patient consent, small Greg explained that type 2 pieces of heart muscle are taken diabetes arises because the body In SVI’s June Heart Seminar, gradually becomes unable to during open heart surgery. Jock Campbell described the respond to insulin due to the high three main themes of his The heart muscle from patients levels of fat in muscle cells. research into heart failure: with and without heart failure He illustrated that many studies the development of will be studied to identify why have shown that exercise can strategies to better prevent the muscle is unable to work reverse or slow the progress of properly in heart failure. heart failure, the study of type 2 diabetes. Aliskiren is a new treatment for the mechanisms of heart Greg’s research group works high blood pressure, and Jock failure, and the evaluation of closely with Bruce Kemp who has has found it increases the new therapies for heart shown that the effects of exercise amount of bradykinin in the failure. are mediated in the cells by a heart. Bradykinin is a hormone protein called AMPK. With collaborators at St. that protects the heart from Vincent’s Health, and Melbourne disease, and he is studying how Research at SVI is focused on and Monash universities, he is Aliskiren is able to increase discovering more about how investigating how general bradykinin levels, and how this AMPK works with the potential practitioners can use a blood property of Aliskiren can be to develop new therapies to test for a protein called NT- exploited for the benefi t of prevent type 2 diabetes and other proBNP to identify people at patients. diseases caused by obesity. congratulations to SVI’s NHMRC 2008 grant recipients Cancer research: Type 1 diabetes Michael Parker research: Carl Walkley Stuart Mannering Jo.. rg Heierhorst Mark Waltham Obesity research: David Izon Greg Steinberg and Manisha’s Bruce Kemp Heart research: Jock Campbell and U.S. grant David Prior SVI researcher, Manisha Shah has been awarded a postdoctoral fellowship by Susan G. Komen for the Cure, the leading breast cancer advocacy organisation in dedication the United States. The three year grant will enable dividends Manisha, under the guidance of Rik Thompson and Mark SVI beat the national Waltham, to continue research average for the second into the cause of bone “ year running with 47% of metastasis, a major problem in Our grant its 19 applications being metastatic breast cancer. awarded funds this year. funding Government research grants students success is are very competitive with an average of only 27% of SCHOOLS a mark applications being funded. awarded The NHMRC announced the tour svi SVI students received some 2009 round of project grant of the Year 11 & 12 school students funding in October and 9 groups prestigious awards during from Genazzano and Xavier excellent of SVI scientists received more 2008. than $5.5 million for research to At the recent Australian and visited SVI to fi nd out more research be conducted over the next 3-5 New Zealand Bone & Mineral about medical research on years. Society Annual Scientifi c 10th September. being However, the end result only meeting, the following students The tour of SVI gave students the tells half the story. NHMRC received awards: opportunity to link concepts carried grant applications take months studied in the classroom with the Jonathan Gooi received the of preparation, writing and latest work in various areas. Roger Melick Young Investigator out at SVI refi nement to ensure that the Award Explanations of the use of protein best case is put forward for the structure in drug design were and the project to be funded. Hasnawati Saleh received the particularly interesting for the SVI Director, Tom Kay said: Christopher & Margie Nordin students who had recently dedication “Those who received funding Young Investigator Poster Award studied protein structure and and those who narrowly missed of our Julie Quach received the function as part of their VCE funding this year should be Wyeth Young Investigator Award studies. commended for their hard work researchers At the XXII International and determination”. Clare Allemand, Head of Biology “Our grant funding success is a Congress of The Transplantation at Xavier said: “It was a wonder- mark of the excellent research Society an award was given to: ful and rare opportunity for the being carried out at SVI and the Pete Campbell who was students to gain a real under- dedication of our researchers,” awarded the TSANZ Young standing of the importance of ” he continued. Investigators Prize. scientifi c research.”

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. ” th . i . xty n . i “We “We i se : i owers d p w i i . rectors, a i ng i nner i i ch i onsh eu of fl i i onate about i s and Lou n l Moore i i rman, John (JT) i i ve hope to the i nued support and i ng relat i nto leukaem i . ewed SVI researcher, Carl ewed SVI researcher, rector, Tom Kay sa Tom rector, i i nted Cha i ng SVI g i ned SVI’s Board of D ned SVI’s i ntroduced Deutsche’s key ntroduced Deutsche’s nterv n the years before her death o SVI D are very grateful for Deutsche cont Bank’s welcome JT to the SVI Board SVI at a celebratory d August people donated to cancer research at SVI JT Macfarlane, who recently j hosted the event wh ABC presenter and SVI Al ambassador, i research customers to SVI’s i about h Walkley Purton’s groundbreak Purton’s research Deutsche Bank’s newly Deutsche Bank’s appo DINNER Macfarlane cemented the bank’s long-stand Deutsche SVI would like to express SVI would like to the its condolences to of family and friends who lost Annette Mascitti her battle with breast cancer in October. Annette was pass Annette’s Annette’s passion help In her memory, more than s In her memory, many people touched by cancer i : r sed i i nner i ddle top) The Foundation i Photo (m The SVI Support Group who ra October d $28,000 at the SVI AFL Discovery Day Breakfast Raising $40,000 for diabetes research at SVI was the focus of the Collingwood vs St Kilda pre-match breakfast in August, hosted by ambassadors James Clement and Luke Darcy. THANK YOU TO OUR EVENT SPONSORS Supported by:

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MC, Luke Darcy interviewing Lila Holbrook about living with diabetes SVI Bloom Fashion Parade Jacqui and Rachel Bloom hosted a unique fashion parade in September, featuring outfi ts made from exquisite Bloom fabrics. The event held in honour of their late mother and founder of Bloom Fabrics, Evelyn, raised $22,000 for cancer research at SVI.

THANK YOU TO OUR EVENT SPONSORS Thank you to our Thank you to our in Unleeshed celebrity models and kind supporters: Dan-Joe Workwear designers: Barry Plant Real Estate Campbellfi eld Concrete Craig Braybrook designer Silverstone Jaguar MJR Photography for Marianne Van Dorslar TS Press Ozone Coffee Shirley Keon designer for Romanin Design Patti Newton Floral Butterfl y Novat Shoes Luci di Bella designer for Bridget Allen Celebrity models, Bev Brock, Lauren Newton, Lauren Newton Deep Hair & Beauty Photography Patti Newton & Melinda Gaze in their Bloom Carmen Licuria designer Fresh Faces Fabric outfi ts. for Melinda Gaze Choreography Thank you to Paul and Bev Brock who designed Victoria University Barbara Licuria’s her own outfi t Fine Art Make Up bridal party

SVI Nissan Golf Day SVI’s inaugural golf day at Albert Park, sponsored by Nissan Fleet was a great success, raising $30,000 for SVI and giving ‘foodie’ golfers an amazing array of gourmet food and wine. THANK YOU TO OUR MAJOR EVENT SPONSOR:

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SVI Tours Have you ever wondered what researchers at SVI are working on right now? Would you like to fi nd out about their work in more detail? It is well worth the effort to come into SVI and meet researchers working on diabetes, arthritis, cancer and Alzheimer’s disease. A tour can be tailored to suit your interest in a particular disease. So get in contact today and arrange a tour by calling 9288 2480 or by email: [email protected]. Getting involved General Donation to SVI: General Donation $ Pledge $ per month per year

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