Australian research makes a play in the post-genomic era

In the biggest party the science community has ever seen, Australia was a wallflower.

While researchers around the world contributed to the mapping of the human genome, Australia's contribution was minimal - a situation that ran contrary to the country's popular view of itself as a bastion of key research.

Now, two years since the draft map of the genome was completed, the genomics landscape has changed. New buzzwords -'post-genomic era', 'proteomics' - are being thrown about to describe the next wave of medical research.

Even Celera, genomics powerhouse and the major player in the Human Genome Project, has expanded its business to include drug discovery and development.

Medical genomics is one facet of genomics that is at the forefront. Spanning research into human genes and their roles in development and disease, as well as examining the genomes of micro-organisms for weaknesses to exploit for drug discovery purposes, the field is rapidly expanding.

How is Australia using the power of the new technology in its medical research efforts?

Competitive

According to Prof Grant Sutherland, former president of the Human Genome Organisation (HUGO) and director of the Department of Cytogenetics and Molecular Genetics at the Women's and Children's Hospital in Adelaide, "research in Australia is highly competitive with research done anywhere in the world."

Sutherland, whose team was one of the few that contributed to the Human Genome Project - it sequenced 2 megabases of DNA out of the total 3200 - admits Australia was one of the few major industrialised countries that did not have a properly funded effort.

According to Dr Sue Forrest, scientific director of the Australian Genome Research Facility (AGRF), Australia's lack of participation in the Human Genome Project was in part due to the lack of high-end genomic facilities.

"The infrastructure hadn't previously allowed us to take part in the Human Genome Project," she says. But, she adds, the establishment of the AGRF now allows Australia to do large-scale sequencing and genotyping studies.

Prof John Shine, executive director of the Garvan Institute of Medical Research, agrees, but cautions that Australia can't afford to lag behind.

"It is very important that we keep developing the infrastructure and not fall behind," Shine says. "The AGRF is providing an excellent national service - we need to foster it, continue to improve and add to it. We are in reasonable shape, but need to keep on top of it."

Forrest claims the challenge now is to come up with sufficient funding for Australian researchers to effectively use the new state-of-the-art facilities. Setting up joint ventures between Australian researchers and international organisations such as the US National Institutes of Health is one solution; linking researchers in academic institutions and biotechnology companies is another.

"The Australian dollar puts us at a disadvantage," Shine says. He notes that reagents and equipment are often priced in US dollars, making research here more expensive. And Australia's spend per capita on medical research still lags behind the US, despite recent increases in the National Health and Medical Research Council budget.

Quantum step

And now that the genome has been mapped, there are new ways of doing medical research. According to Shine, "Having the whole human genome database available has made research a lot easier. It has been a quantum step in the progress of our understanding of the genome and a quantum change in the way we do things.

"A decade ago, researchers spent 90 per cent of their time cloning and sequencing and maybe 10 per cent on the computer analysing the data. Now 50 per cent of the time is spent on the computer analysing the databases."

Dr Matthijs Smith, director of genomics at Cerylid Biosciences, agrees that biological research is becoming increasingly dependent on computers.

"The Human Genome Project generated an extraordinary amount of data and changed dramatically the way experiments are done," he says.

"Gene hunting will increasingly be done on a computer. But you'll always have to come back to the biological function."

Australia's genomic researchers have had access to both the public and the private databases of the Human Genome Project since the NHMRC bought the first license for grant-holder access to the Celera database in 2000.

Forrest says that both were invaluable tools for researchers and each had different information that could be utilised in different situations.

"The Human Genome Project has given us another tool for discovery," says Prof Greg Collier, chief operating officer at Autogen, a Melbourne genomics company focussed on using functional genomics to identify 'druggable' targets for obesity and diabetes, as well as anxiety and depression. "Ultimately we are interested in the biology of the disease." A typical project at the Garvan Institute that takes advantage of everything the new technology has to offer is its prostate cancer research program. Shine claims that the Garvan has "arguably the world's best prostate cancer tissue banks, with the associated clinical records and patient histories."

Using microarray analysis, researchers at the institute are screening samples to identify genes that are clearly turned on in particular types of cancer. Once identified, the protein function can be studied using a variety of techniques, and therapeutic targets can be identified and developed.

"Array analysis gives us an undreamt of number of clinical targets," Shine says. But funding shortages, not just a problem in Australia, mean that not everything can be followed up.

New links

The funding shortfalls have led to new interactions between institutions and industry.

Almost every university and institute in Australia now has links with biotech companies, often creating them as spin-offs from their research programs. In some cases this creates a conflict of resources as the new companies are competing for funding and for qualified people with the institutions that fathered them.

But the obvious advantage to such close links is a change in attitude, and recognition that biotech companies are capable of performing research to the same high standards as academic researchers.

The CRC for Discovery of Genes for Common Human Diseases (the Gene CRC), is a big player in medical genomics in Australia and an excellent example of the increased cooperation between industry and academia. It was formed in 1997, with a mission to "bring together Australia's strategic genetic resources to identify disease susceptibility genes" in a range of different diseases.

The Gene CRC consists of several major research institutes including Murdoch Children's Research Institute, Walter and Eliza Hall Institute for Medical Research (WEHI), Queensland Institute of Medical Research (QIMR) and the Institute of Molecular Biosciences (IMB) at University of Queensland, as well as biotech company Cerylid Biosciences and the Menzies Centre for Population Research.

The Gene CRC has a diverse range of projects ranging from cancer, metabolic disorders and autoimmune diseases to issues of women's health and public health. Major diseases being studied include Type 1 diabetes, multiple sclerosis and endometriosis.

"The Gene CRC has tried, through its selection of projects, to focus on areas where Australia has a competitive advantage," says Cerylid CEO Dr Jackie Fairley.

Long term

In some cases the advantages are particular skills, and in others resources, such as the large patient cohorts represented by the Menzies Centre or the Twin Registry organised by Dr Nick Martin at QIMR.

"These are large, long-term projects," says the Gene CRC's CEO, Dr Andrea Douglas. "It can take a while to accomplish results."

There's the CRC's endometriosis project, for example. Endometriosis is a severe condition affecting about 10 per cent of women that causes severe pelvic pain and fertility problems. The CRC has assembled more than 3000 sister-pairs and family members affected by the disease, with a total of more than 10,000 patients in the study.

"Internationally, this is the largest cohort of women affected by the disease," Douglas says, adding that this gives the CRC team the best chance of finding genes involved in endometriosis. Last year, the Gene CRC and Cerylid Biosciences announced a major collaboration with Oxford University and UK biotech company Oxagen. The collaboration is known as the International Endogene Study and is the largest endometriosis study in the world. Dr Douglas predicts that gene discoveries will be made in the next one or two years.

Similar results are expected from the other major projects at the gene CRC, including the multiple sclerosis program. Douglas explains that it can take a long time just to obtain sufficient numbers of patients to do the studies.

The Gene CRC is soon to apply to the Federal government for a second round of funding. A shift in emphasis is likely to happen as this occurs, leading to more focus on functional genomics and drug discovery and less on gene discovery. This mirrors the shift in focus of medical genomics from discovery to application.

The importance of research and development using genomics-based approaches can't be overstated.

Dr Deborah Rathjen, CEO of Adelaide-based company Bionomics, says that these technologies will ultimately lead to a "more personalised approach to medicine." She believes that it is not simply enough to know what a gene is anymore, but also what it does, what pathways it is involved in and how it is controlled. By examining these factors and others, researchers can identify potential targets for therapeutic development.

Niche

Bionomics is using genomics-based approaches to identify genes and pathways involved in epilepsy, breast cancer and angiogenesis. The company has patent applications on more than 230 genes and has discovered several important genes involved in breast cancer and epilepsy. It has several clinical collaborations, including one with Grant Sutherland's team.

The company has also formed several industry alliances both in Australia and overseas, including one with US company Hybrigen, which is doing drug discovery research using angiogenesis and breast cancer genes identified by Bionomics. According to Rathjen, Bionomics is in the process of generating more international partnerships with pharmaceutical and biotechnology companies this year.

The consensus in the industry is that Australia needs to make sure that it keeps up with genomics - technologically, at least. While countries like the USA have a far greater ability to fund genomics research, Australian biotech has advantages not found elsewhere in its close interaction with clinical medicine and access to unique patient cohorts.

"We're competing against a very large group of companies internationally," says Autogen's Collier. "It is important that Australia finds its niche."