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Cash-Strapped COMBREX Seeks Funds to Improve Understanding of Pathogenic Gene Function

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Organizers of the nonprofit Computational Bridges to Experiments, or COMBREX, project are seeking funding to support experiments that will add to the existing body of knowledge on the functions of pathogenic genes in several microorganisms.

Richard Roberts, chief scientific officer of New England Biolabs and one of the project's founders, told BioInform this week that the COMREX team would like to explore the functions of potentially pathogenic genes in organisms like Helicobacter pylori, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis.

He said the project would look to experts in the function prediction field to identify potential genes for study. The organizers are particularly interested in studying the functions of genes that play a role in multiple pathogens — for example a gene than has 100 homologs — since there’s more value to be had from such characterization than would be gained from looking at genes with fewer homologs.

Once it has identified potential genes, COMBREX will then provide small grants to research labs or undergraduate teaching programs to fund experiments aimed at validating predicted functions, Roberts said.

For now, however, those plans are in limbo as the project has run out of funds and its organizers are awaiting the outcome of several funding applications; all the while seeking additional support from other sources. In addition to Roberts, researchers from Boston University are also involved with COMREX.

COMBREX developers have been seeking a long-term source of funding since the expiration last year of a $4 million grant from the National Institute of General Medical Sciences under the 2009 American Recovery and Reinvestment Act.

COMBREX was set up in 2009 to provide small grants to fund experiments aimed at validating computationally predicted gene functions; serve as a host for high-quality functional predictions; and to provide traceable gene annotations (BI 5/18/2012).

Roberts told BioInform that the project needs between $2 million and $3 million per year to maintain its operations and fund experiments. But it’s been difficult to garner that kind of support since COMBREX doesn’t meet the criteria for R01 funding set forth by the National Institutes of Health’s study sections.

The organizers had previously tried to apply for an R01 grant from the NIH but were turned down because portions of the project — such as support for the development of gold standard database of experimentally verified gene protein products — did not fit the stated criteria, Roberts said. They’ve also looked into funding opportunities from the Department of Energy and the National Science Foundation, even crowd sourcing, to no avail, he said.

But COMBREX developers aren’t giving up yet. They’ve put in a funding application to the National Institute of Allergy and Infectious Diseases, which is currently pending, Roberts said. He also told BioInform that his team amended and resent its application to the NIH and is awaiting the institute’s decision. He also hopes to garner some support from members of the biocuration community at a meeting in Cambridge, UK later this year.

Meanwhile, the COMBREX team has continued to develop the database and accompanying algorithms, Roberts said.

Activities include a collaborative project between NEB and China’s Fudan University where students at the institution worked on characterizing some genes for the resource, he said. Also, Roberts has worked on characterizing some genes and proteins involved in restriction modification in bacteria using a separate Small Business Innovation Research grant.

The Case for COMBREX

The current next-generation sequencing boom provides at least one justification for why COMBREX should continue to exist, according to Roberts.

“We are spending an enormous amount of money sequencing DNA and you have to ask, 'What is the point of sequencing all this DNA if you are not going to try to work out what the genes in it are doing?'” he said.

Also, compared to the amount of R01 funding needed to establish a working lab specialized in studying particular genes, “one might have thought that in times of austerity, [COMBREX] would be the kind of project that would be viewed as being rather a good use of money,” he noted.

Roberts further argued that COMBREX could provide a solid base on which larger and more complex gene function studies could be built.

Microbial genes are “simpler” and “many of the genes that you find in microbes, you find in all the higher organisms, too,” he said. So, “if you can establish the methodology … [and] get the gold standard database going … in microbes then it should make it much easier to extend it into higher organisms later on,” a step which he and his co-organizers hope to take within a few years if they can secure a stable cash flow, he said.

He also noted that a more in-depth analysis of genetic components of the microbiome makes sense in light of the fact that human health and disease are influenced by the microorganisms that are part of the body.

Historically, people tended to overlook microbes, he said, but now that the “microbiome is recognized to be pretty important, it may be possible to get the human research community more interested” in COMBREX.

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