Have you ever been told you couldn’t get funding because you weren’t asking for enough of it? Sounds absurd, right? That’s how Richard J. Roberts of New England Biolabs in Massachusetts felt when he heard over and over from funding agencies that they simply didn’t have a mechanism to provide him with the series of small grants he was asking for—each $5,000 to $10,000 to annotate microbial genes of unknown function. He was hoping to provide the modest funds to labs that could quickly and cheaply annotate a wide range of genes. But the National Institutes of Health (NIH), the National Science Foundation, even the US Department of Energy all said the same thing—they couldn’t support such a project “because the amounts of money were smaller than they were...
“I thought it was stupid [and] ridiculous,” he says. “To say, ‘That’s a good idea, but we don’t know how to fund it’—that makes no sense.”
The “good idea” was to start a type of Wikipedia for bacterial and archaean genes—create a database listing the unknown genes and predictions for what they do, and ask biologists to pitch in to identify their functions. The end goal: Gain a comprehensive understanding of microbial biology and possibly discover genes with useful medical or agricultural properties.
After nearly 5 years of campaigning towards this goal, Roberts’s luck finally turned. The NIH established a new program as part of the American Recovery and Reinvestment Act of 2009. The “Grand Opportunities” (GO) grants program provided 2 years of funding for large “biomedical and biobehavioral research endeavors,” and with a slight tweak to his funding strategy, Roberts’s gene annotation database fit the part.
Roberts and two other PIs (biotechnologist Martin Steffen and computational genomicist Simon Kasif of Boston University) drafted a proposal for a single GO grant, which they would then distribute in smaller chunks of funds to labs that want to participate. The proposal was granted for $4 million.
Largely based on Roberts’s own ideas, outlined earlier in PLoS Biology in 2004 (2:0001–2, 2004), the project entails starting an online database of microbial genes of unknown function, and seeding it with existing bioinformatics-based predictions for what those genes do from the National Center for Biotechnology Information and other sources. Experimentalists could then peruse the database for genes suspected to play a role in their particular area of research, while computational biologists could look to fill in missing predictions. The researchers could then ask Roberts and his team for a cut of the funding to work on those genes.
It is to be “a community effort,” Roberts says. By recruiting the help of researchers in different fields, annotating microbial genomes “is a relatively straightforward thing to do if you have the substrates and the assays,” he says. It’s “everybody doing their little part,” adds Steffen. “[We’re] essentially forming a consortium to make [validating gene function] high throughput by getting the right project into the right lab’s hands.”
The project already has several labs on board, each with its own focused area of expertise. “It’s a rational way to go about it,” says molecular biologist Thomas J. Silhavy of Princeton University, whose lab focuses on envelope biogenesis and components of stress and signal transduction pathways. “In theory, we could [test these predictions] without a whole a lot of effort” because we already have the lab set up to study those types of genes.
The project has also recruited the help of Manuel Ferrer of the CSIC Institute of Catalysis in Madrid, who recently developed the reactome (Science, 326:252–57. 2009), which allows researchers to screen thousands of functions simultaneously—“a potentially breakthrough technology, which might go a long way to getting us started,” Steffen says.
Molecular biologist Milton Saier, who specializes in transporter proteins and has also agreed to participate in the project, notes that it could be a great opportunity for students. While he already has some 15 graduate students in his lab, there’s always room for more, he says. “These are doable bite-size pieces,” Steffen agrees, making them particularly attractive projects to rotation students, for example, who could get “something pretty significant to further their career” with just a few months worth of work. “I think there’s going to be significant economic and medical impacts,” he adds.
“There is so much sequence out there and so many genes, and we have no idea what they’re doing that there’s no need for competition,” Roberts agrees. “There is just no shortage of stuff to do.”