Functional genomics is exactly what it says on the tin: a growing field in which the staggering amounts of data gained from the multitude of international genomic sequencing projects are brought together to work out what it is that genes do.

Expression cloning is the one of the best methods available that allows scientists to ask some very important questions, to understand this core problem of what genes do.

Complementary DNA (cDNA) libraries using retroviral vectors have been used for this purpose for many years, but a consortium of researchers and institutes - the University of Queensland's Diamantina Institute, based at the Princess Alexandra Hospital campus in Brisbane, UQ's Institute for Molecular Bioscience and the University of Adelaide - have now come together to create a facility that uses this method in a much faster, simpler and more flexible way.

Tom Gonda and his colleagues call the project ARVEC, or arrayed retroviral expression cloning. The consortium has received several large grants from the NHMRC, the ARC and more recently from the Australian Cancer Research Foundation to establish a new, automated system at the Diamantina that they hope will allow Australian researchers to discover genes of biomedical importance.

"The idea of establishing this facility is to make it as generically applicable as possible," Gonda says. "It's not so much that we are designing it to do one specific type of assay or one kind of experiment. There are lots of people in the consortium and lots of our collaborators are interested in doing screens like this, so the idea is to make it as flexible as possible."

The project involves two stages: one, a robotics platform, is already up and running. The other is the creation of a cDNA library representing all of the genes in the human genome (although it will not be possible to represent all of the splice variants at this stage).

"The idea is to make a library, ultimately with all 20-odd thousand genes in the human genome represented, and to do this in an arrayed format, basically 96-well plates with one representative cDNA per gene," he says.

The consortium is not actually creating a new library, as it is far easier to buy a set of cloned open reading frames, which it has done.

"We've got about 12,000 at the moment, about half a genome's worth, and we'll hopefully acquire the rest as they are released. What we have to do now is to transfer each of those individually into a lentiviral vector and again we'll have a whole series of 96-well plates with one lentivirus containing one gene, and we will know where and which gene it is."

Robots will be used to transfect the viral vector DNAs, along with viral packaging constructs, individually into 96-well plates containing packaging cells. These will then make the lentivirus from the DNA, releasing the lentivirus into the supernate.

"It will incubate the cells - we have incubators as part of the robotics platform - and then we will harvest the virus from those cells, and as a separate run we will use that virus to transduce target cells, which after an appropriate incubation period will be assayed for whatever phenotype we are interested in."

The robotics platform includes a high-content imaging device, which works like an automated fluorescence microscope, as the readout system, he says.

"The kind of assays we use are those that have fluorescence as a readout in one way or another. Typically we will be staining cells with fluorescent antibodies. There are all kinds of things you can address doing that, but the main advantage of doing things this way is that we are not looking for cells that have any particular growth advantage or so on - we are only putting one gene in each well of target cells."

The consortium is currently fine-tuning the robotics platform, most of the components of which were provided by Millennium Science, and optimising processes such as virus production.

A small pilot library of about 1500 cDNA clones has been created and the first sets of transfections are now being tried.

"So far that's looking pretty good so the next step will be to screen this pilot library that we've made," Gonda says. "We are using some pretty simple screens just to show that it works."

A $3.2 million grant from the ACRF is helping further research, with part of the fund going towards new equipment for the new ACRF Comprehensive Cancer Genomics Facility, which will be based at the Diamantina and run in association with the Queensland University of Technology.

More robotics platforms are planned, as is the purchase of siRNA and shRNA libraries to identify drug targets.