The $6 million wallaby: push continues for homegrown genome project

In what Francis Collins has termed "an unprecedented offer," the US NIH's National Human Genome Research Institute has offered to share the cost of generating the sequence of the tammar wallaby genome despite going ahead with an American opossum species as the chosen marsupial for comparative genomics.

The wallaby has been designated a 'moderate priority' species, compared with the high priority status of the opossum, Monodelphis domestica.

According to marsupial genomics researcher Prof Jenny Graves, Monodelphis is a well studied marsupial in US labs. But not much is known about the South American species in its native environment, she said. In contrast, the tammar wallaby Macropus eugenii has been intensively studied both in the lab and in its natural habitat.

The collaboration would see Australia and the US working together to generate 1-2 times high quality coverage of the wallaby sequence -- a task made easier by the larger scale Monodelphis effort, but still requiring a minimum of 5.5 million sequencing reads to cover the 3.5 billion base pairs of the wallaby genome.

But Australia risks being left out in the cold if it doesn't take up the offer to participate in the project, particularly with the generous offer of support from the US team, say leading genomics scientists who are trying to raise AUD$6 million in support of Australian participation.

"The message is that the NIH has faith that we can do this and has offered is this opportunity. So let's take it with both hands and run with it," says Dr Sue Forrest, the director of the Australian Genome Research Facility.

Graves, who is head of the Centre for the Kangaroo Genome, which received ARC funding earlier this year to begin mapping the tammar wallaby's genome, says she is extremely buoyed up by the US offer to co-fund the project. "This could be a big opportunity for Australia to not just hand over our DNA to the US, but to do it ourselves," Graves says. "I think we'll get a lot out of it."

Now that Collins has given the green light to the project, Forrest is swinging into fundraising mode. She is hoping that the federal and state governments and funding agencies are willing to kick in up to $1 million each. Qantas has also been approached to sponsor the project, and there are plans to go after philanthropic organisations, conservation groups and zoos to try to pull in the funds. Sequencing equipment supplier Applied Biosystems is also keen to support the project, Forrest says.

"We'd like to get some commitments in the next couple of weeks," she says, stressing that as the project is likely to run for a couple of years at least, the funding will not be required all at once. But support from the federal level, at least, has been non-committal so far. While the new Centre for the Kangaroo Genome was recently awarded $2.6 million from the Australian Research Council, this has been earmarked for genetic and physical mapping efforts and for setting up an expressed sequence tag (EST) database rather than sequencing.

Federal Science Minister Peter McGauran told Australian Biotechnology News he is "strongly supportive of Prof Graves' groundbreaking work." But McGauran is more guarded when asked about the possibility of federal funding for the genome sequencing project. "Further financial assistance will depend on applications to funding bodies such as the ARC being again successful. I cannot predict the outcome of these applications given that they take place on a competitive basis and are assessed by peer review."

Forrest says AGRF calculations estimate that $6 million is enough for Australia to complete about three million sequencing reads -- about half of what is required for one times coverage. The funding would pay for the cost of personnel and consumables, while the four new high-throughput sequencing instruments required would come out of the AGRF's Major National Research Facility grant.

According to Forrest, the AGRF currently has a workload of 200,000 reads a year, with the capacity to expand that somewhat. The current plan would be to spend between two and three years generating the sequence, she says, given that Australia's capacity to sequence is around a tenth of the big sequencing labs in the States.

The upgraded capacity won't go astray either, Forrest says. "We hope it would set a precedent for future collaborative efforts," she says. "It's a fantastic opportunity to gain a reputation as high-quality sequencers."

The project will also bring with it opportunities for training, particularly in the area of bioinformatics. "There are a lot of downstream activities to benefit, and lots of potential collaborations," Forrest says.

But what are the implications for Australian genomic science if the funds can't be raised for the project?

According to former AGRF director Prof John Mattick, the need for Australia to participate in the project is important for two reasons.

"Unless we do the genome of the wallaby, Australian marsupials will no longer be the focus of marsupial research," he says. "It's also a symbol of Australia's ability to participate in international projects -- we can't even do our own species."

Mattick says the failure to sequence an Australian marsupial would not go unnoticed by the international scientific community, and it would be seen as an act of hypocrisy that the country with the vast majority of marsupial species was unwilling to participate in the sequencing project.

"Australia likes to think it's doing leading-edge science, but in the biggest transition in scientific history, the Human Genome Project, Australia did diddly-squat," Mattick says bluntly. "This is our chance to make a contribution."

An ironic twist to the situation is that the AGRF was set up precisely to allow Australian researchers access to cutting edge technologies and enable participation in global efforts.

"If we were not able to raise the funds, then I would say the AGRF would keep going as a medium-sized facility... but lacking the opportunities to collaborate on internationally focused projects," Forrest says. "We'd be doing everyone else's work and not using our skilled science base to drive bigger science for the country. We're a major national research facility, not a minor one."

Mattick says he believes there is a lack of commitment to doing significant genome projects in Australia, due to a lack of appreciation of the role of genomics as an information science in its own right.