From Stickleback to interactome

Lisa Espenschade
BETHESDA, Md.—TheNational Human Genome Research Institute (NHGRI) in late summer announced twogrants illustrating the diversity of genomics research: one program, at Stanford University, investigates vertebratediversity through stickleback fish. The other, based at Boston'sDana-Farber Cancer Institute (DFCI), uses a viral model to consider how geneticvariations and pathogens combine to induce disease states in cellular networks.

The two grants were made through NHGRI's Centers ofExcellence in Genomic Science (CEGS) program, with $16 million to DCFI and $14million to Stanford. The varied topics are no accident. Although Jeff Schloss,NHGRI's program director, technology development, says the Institute tends tofund highly focused projects like large-scale sequencing or developing HapMaps,CEGS aims for ideas "that will have a large impact in genomics that can't bedone under standard grants programs" or that makes a large and exportableadvance in genomics, as did microarrays.

Although Schloss says science drives the program, CEGS alsocarries a training element, expecting institutions to involve post doctoralresearchers and graduate students. "Many of these grants," says Schloss, "haveended up being at institutions where there's already a significant presence ofgenomics, but even so, they've helped to reinforce or strengthen the genomicspresence and the ability to advance genomics research more on campus." Projectsshould also involve people from minority communities: beyond drawing moreminorities into science, Schloss says, NHGRI has selfish reasons. Genomicsresearch inherently addresses genetics in various communities, meaningscientists need to work effectively with societal expectations that maystigmatize "bad genes" or affect healthcare.

With the Stanford program entering its second five-yeargrant period, David Kingsley, professor of developmental biology, Howard HughesMedical Institute and Stanford School of Medicine, has seen results through theminority program. "Because we have an existing program," he says, "we have seenthe successes that come from students doing research, writing papers, and beingabout to talk about that in their essays and interviews" when they apply tograduate programs in medicine and other fields.

Kingsley sees stickleback fish—which are studied in dozensof labs around the world—as a valuable new model for investigatinglong-standing problems of genetic mechanisms with potential relevance tohumans.

"This is an incredibly exciting time in genetics andgenomics," says Kingsley. "Large-scale sequencing has made it possible to seethe genome of lots of different animals, including humans. I think that it'sstill very hard to stare at a genome sequence and know what all the base pairsare doing, and studies of model organisms are going to help us interpret andsort through that flood of genome information that's coming from the genomeprojects. So genomics plus genetics is much more powerful than either onealone."

Meanwhile, Marc Vidal, associate professor of genetics atDCFI and Harvard Medical School, says that the DFCI CEGSbuilds on the Center for Cancer Systems Biology, founded in 2004 to encouragemore integrative work between scientists wanting to understand disease in thepost-genomic era. He hopes to see value to drug discovery from research intohow gene products, proteins, RNA, and other macromolecules interact withincells by analyzing the human interactome network and protein-proteininteractions as well as how genetic differences between people affect theirreactions to environmental perturbations.

Lisa Espenschade

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