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The Umbrella Institute

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If all that springs to mind when you hear "Australia" are kangaroos and coral reefs, think again. Known for its cutting-edge translational research, the Hunter Medical Research Institute centered in Newcastle, New South Wales, is leading the way in a country taking big steps toward translational medicine. Started with seed money from the state government, HMRI brings together a group of diverse biomedical researchers and clinicians from the University of Newcastle, Hunter New England Health, and Calvary Mater Newcastle Hospital. Located mere kilometers from one another, the disparate locations are soon to be consolidated into one building. The project is estimated to cost Aus$90 million (US$60 million) and will be constructed on 13,000 square meters of the Rankin Park Campus of the Hunter New England Health Service.

While HRMI is known for its wide-ranging research, it does focus on a few choice areas. The most recent, a program in information-based medicine started several years ago by Hunter scientists Rodney Scott and Pablo Moscato, brings that number to seven: brain and mental health; cancer; cardiovascular disease; information-based medicine; pregnancy and reproduction; public health; and viruses, infections/immunity, vaccines, and asthma. "The Hunter has always been recognized for its focus on clinical research, about taking a clinical problem and addressing [it] as opposed to being at the basic biomedical end of the research spectrum," says Director Maree Gleeson. "Our strengths are very much in how to implement good clinical research."

HMRI was set up 10 years ago as a joint venture between the University of Newcastle and the Hunter New England Health services "to provide an umbrella organization to ensure that biomedical researchers from the university could be integrated with healthcare as well as clinical research being conducted in the hospital," says Gleeson. "The model of HMRI was really to bring together researchers that span the whole spectrum of health and well-being — from biomedical science through to clinical trials through to population and public health. It brings together health education, health services, and health research into a single model."

Initially supported by an Aus$600,000 grant from the state government, HMRI has matured rapidly during the past 10 years. Among a list that includes 11 state-supported research institutes, HMRI now holds the number three spot in terms of quality of research and continued grant funding. Even though it was a new idea for how to conduct translational research, says Gleeson, it works — and in the process it has become a state-wide model. "The reason it works is that having the education, the research, and the clinical services integrated ensures very fast translation of that research into better healthcare practices and better health outcomes."

While collaborations cut across the entire country as well as internationally, researchers are mostly located across several campuses in the area of the University of Newcastle. But plans are in the works to build an entirely new facility to house the growing number of affiliated researchers and clinical scientists by 2012. "People often say to us, 'Well, why are you doing that? The model has worked so well without bricks and mortar,'" Gleeson says. But in the past decade, she notes, the institute has grown a lot. "When you've grown from 100 to 700 in 10 years, you actually have to find somewhere to house them," she says. "We're building bricks and mortar really to give them a world-class medical research facility to work in."

Biofx to the rescue

Three years ago, the institute added a bioinformatics and information-based medicine program. "It was set up specifically to provide [to] those research programs access to bioinformatics and molecular genetics [research]," Gleeson says. The area that the program has taken on first has been cancer — specifically breast cancer, prostate cancer, and melanoma. The bioinformatics team has also been involved with neuroscience research, brain imaging, and multiple sclerosis. The program is co-led by Rodney Scott, who works as a medical geneticist at the University of Newcastle, and Pablo Moscato, a bioinformatics specialist also affiliated with the university.

Scott is using the bioinformatics program to analyze large, clinical datasets. His aim is to identify disease predisposition and risk, and use the data to establish personalized treatment guidelines based on genetic information.

In previous clinical studies, Scott had been working with Moscato and "it had come to the stage in the work … that we were gathering together huge amounts of information and it was very difficult to analyze by just looking at it and doing simple statistical analyses," Scott says. "It became very apparent that we needed some sort of bioinformatic input into analyzing large collections of genome-wide gene expression data and, more subsequently, genome-wide association study data."

In treating diseases, the most important thing to understand is that one disease might have many different genotypes, Scott says. Using only the statistical approach to analyzing gene expression and GWAS data, he says, "you can't link pathways together." Being able to apply a bioinformatics analysis to large sets of disease data would help researchers "tease out the information that's related to disease."

A problem with GWAS is that these studies are mined only for genetic susceptibility information, but not for information about which pathways are associated with the disease in question. "If you interrogate two or three particular pathways, you may in fact identify something that's much more useful in the interpretation of genome-wide association studies than just individual genes," Scott says. "We're currently putting a lot of effort into that."

Over the last year, one area of focus has been on melanoma, and specifically on performing gene-expression profiling on melanoma cells or samples from patients. "When we look at the data — just eyeballing it using gene expression analysis and observing what changes we see — it's very difficult to categorize particular individuals into groups," Scott says. "When we're looking at a disease like melanoma, we're not actually looking at one disease. We're probably looking at a series of different diseases that have a very similar phenotype." At the molecular level, these differences are likely to have an impact on what will be the best treatment for a particular individual. "What we're aiming at is individualized medicine," he says, with the goal being to develop therapies that are appropriate for each genetic subcategory of melanoma.

"We're setting up the model for cancer, but it's equally applicable to other diseases — bioinformatics and acquisition of large data sets to try and identify just how many types of diseases there are and what the underlying factors are that result in a predisposition to disease," Scott says. He's recently begun a study of schizophrenia, is in the middle of a large study on macular degeneration, and just finished an Aus$1 million study on the genetic basis of multiple sclerosis.

Hunter Medical Research Institute
Newcastle, New South Wales, Australia

Director: Maree Gleeson
Established: 1998
Size: A new 13,000-square-meter building will be constructed to house more than 340 researchers.
Staff: Almost 700
Funding: An initial Aus$600,000 came from the state government.
Additional state grants over the last three years total Aus$7 million.
Focus: HMRI focuses on translational research in seven main areas: brain and mental health; cancer; cardiovascular disease; information-based medicine; pregnancy and reproduction; public health; and viruses, infections/immunity, vaccines, and asthma.
Facilities: HMRI has a variety of shared resources, including a localized clinical trials unit, a research register, a schizophrenia register, the Australian EEG database, a biomolecular research facility (which houses protein sequencing, 2D gel facilities, and a MALDI-TOF mass spectrometer), the NSW Center for SNP Analysis, and a biohazardous human tissue handling facility.

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