Lorne Genome: Gaps in the genome

Melissa Trudinger takes a candid look at the state of genomics research in Australia.

Australia has slipped behind other countries in genomics research, with little money available to fund large scale genomics projects, and apparently little interest -- with one notable exception -- from the state and federal governments in the science.

It's a frustrating situation for genomic scientists, and also for others who would like to avail themselves of the substantial resource that genome sequence data and maps provide to the biological sciences.

"It's disappointing that Australia hasn't made bigger contributions in this area," says Prof John Mattick, from Queensland's Institute of Molecular Bioscience. "All of our sciences rely on the contributions of other countries."

Australian researchers had little to do with the Human Genome Project, and since the end of that flagship project and the flowering of genome projects to sequence a wide variety of organisms, has not substantially increased its participation. In fact, Australia has participated in only a couple of major genome projects to date -- the bovine genome project and the Brassica genome project -- and has missed the boat on others. Last year, the US National Institutes of Health's National Human Genome Research Institute (NHGRI), which has coordinated many of the genome sequencing projects to date, chose to sequence a US marsupial -- the opossum -- rather than an Australian species, despite Australia being home to the vast majority of the marsupials. And the Americans are also sequencing the platypus, another iconic Australian species, with little or no input from Australian researchers.

Can't fund, won't fund

According to the genome research community in Australia, though, it's not from lack of interest but from lack of funding of the scale required to participate in the expensive programs. Neither the National Health and Medical Research Council nor the Australian Research Council, Australia's two major research funding agencies, have the funds available for large-scale genomics projects, although funding is available through standard grants schemes for smaller targeted projects aimed at identifying specific genes, or sequencing the small genomes of pathogens.

"The ARC won't fund broad genome sequencing projects, although they will fund projects answering specific questions with direct biological outcomes," says Sue Forrest, the director of the Australian Genome Research Facility, a major national research facility that provides sequencing, genotyping, microarray and other genetics and genomics services to Australian researchers. "It's disappointing, but at least it's a policy."

The NHMRC provided around $8 million in funding in 2001 for four projects in medical genomics, and is currently seeking expressions of interests for another $10 million round of funding, this time in medical bioinformatics, genomics and proteomics. But large-scale genomics projects typically cost tens of millions of dollars, and there is nothing set up in Australia to provide that kind of funding.

Playing possum

Embarrassingly, a bid to sequence the tammar wallaby genome at a low level of coverage (2X) to supplement the sequence data from the opossum almost didn't go ahead due to the lack of funding available for the project, despite a pledge of matching funds from the NHGRI. The Victorian government saved the day, upping its initial pledge of funding from $1 million to $4.5 million, which along with the $1.5 million in support, mostly in the form of equipment and reagents, from Applied Biosystems, was enough to get the project off the ground.

"It's particularly disappointing that we have found it difficult to raise funding to sequence our national icon, despite the US offer to pay half," says Mattick, who is on the board of the AGRF, which along with the ARC's Special Research Centre for Kangaroo Genomics led by Prof Jenny Graves at the ANU is spearheading the wallaby genome project. "With the notable exception of the Victorian government, none of the other state or federal governments have seen the importance of doing this."

The problem, according to Mattick, is a lack of understanding by research funding agencies and governments of the importance of genome research as an underpinning to other biological sciences research. He says the view that genes lead to proteins is a limited one, and that more information on the workings of the genome is required.

Strategic benefits

One way or another, the consensus from genomics researchers is clear -- they would like to see more money for large-scale genomics in Australia. And it isn't likely that the money would be thrown at random projects -- the genome projects currently being planned or conducted bring with them strategic as well as scientific benefits. According to Forrest there are currently three or four top quality genome projects in the planning stages (see separate story, 'True Blue Genomics') with Australian leadership or participation.

"It's not as if we'd be sequencing any old genome -- these are very strategic choices for biological, evolutionary and commercial reasons," Forrest says. "For projects to be proposed they have to be important just to get the consortium together."

University of Melbourne geneticist Phil Batterham, who is behind two insect genome projects -- the sheep blowfly and the cotton bollworm moth -- with the promise of substantial agricultural benefits downstream, says genomics will provide a solid platform for continuing research into insect pests in a more targeted fashion, to identify the mechanisms of developing resistance to insecticides, vulnerable points in the life cycle, and so on. "For some of these organisms, tens of millions of dollars have been spent so far with little effect," he says.

Finding funding

One thing to consider is how to fund the genome projects. Mattick says it would be best to fund them completely separately from the existing research funding agencies -- and that it's important that any funding designated for genome research doesn't result in a diminishing of general research funding by the NHMRC or ARC. "There should be a targeted genomics program in Australia that could be modelled on the either that of the US or of Canada," he says.

While the US genomics program, which is coordinated by the NHGRI, takes a strategic look at what genomes should be sequenced and why, Genome Canada (see separate story, 'O Canada!) provides funding to projects submitted based on merit. "It would be good to look at the stronger aspects of those two countries," Mattick says.

In any case, he says, the genome portfolio should be mixed, with projects of economic and scientific interest -- preferably both. Budget-wise, Mattick believes that Australia should invest about half the amount that Genome Canada has to date, given that Australia is about two thirds the size of Canada. The Canadian government has so far invested C$386 million into Genome Canada, with a further C$469 million raised through contributions from provincial governments, industry and foreign support.

Forrest says she can see the need for Australia to have about 10 major sequencing projects underway, in addition to other kinds of large-scale genomics projects such as linkage studies. In addition, smaller scale studies to map genomes and generate databases of ESTs would be necessary for biological discovery, she says.

"If we can fund manageable genome projects, then we have a significant advantage in capturing intellectual property locally -- that's a major issue," Forrest says. "We're not asking to sequence everything under a rock in this country -- it's about choosing relevant projects. If we don't do these projects, we will find it difficult to stay in or even maintain our position -- we risk slipping backwards and losing our position of strength and scientific capability.

"For a country that has such high standards of research, it's a travesty, really."