UCSF Research into Tiny Organisms Has Big Implications

By Robin Hindery

Thanks to a recently awarded federal grant targeting “unconventional” research, two UCSF scientists are breaking new ground in the field of bacterial genetics. The scientists, Carol Gross, PhD, a UCSF professor of cell and tissue biology, and Nevan Krogan, PhD, a UCSF assistant professor of cellular and molecular pharmacology, will receive up to $800,000 over a four-year period as part of the new Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) program of the National Institutes of Health (NIH). According to the NIH, the program “targets investigators who are testing novel, unconventional hypotheses or are pursuing major methodological or technical challenges.” The projects selected for funding must be “substantial in terms of both the size of the scientific community affected and the magnitude of [their] impact on the community,” according to the NIH website.. Gross and Krogan say their work has major implications for the scientific community. “There are potentially really significant outcomes, not only for what we’ll find, but we also expect it will really change the way prokaryotic biology is done,” said Gross, referring to the study of organisms that lack nuclei – a group that includes bacteria. The two scientists are focusing specifically on E.coli, a bacterium commonly found in the lower intestine of warm-blooded animals. Later, they plan to expand their research to include S.pneumoniae, a pathogen linked to pneumonia, bacterial meningitis and ear infections. In order to study E.coli, Gross and Krogan are developing methods to remove the bacterium’s genes two at a time to observe what happens. By doing so, they hope to develop the first comprehensive picture of how E.coli’s 4,000 genes relate to and interact with one another. The pair’s research also has evolutionary implications: It could provide insight into how bacteria may be genetically linked to more complex organisms such as plants and animals, which are known as eukaryotic organisms because their cells contain nuclei. “This would be the first type of dataset [compiled] for prokaryotic cells,” Krogan said. “We could then look at global trends, the architecture of eukaryotic cells, to see if it is similar to [that of] prokaryotic cells.” The scientists have been working on their project for about a year, but when they applied for the EUREKA grant, they had “just a few preliminary results” to show for their efforts, Gross said. “There’s no way we could have gotten funded with anything else except for this [NIH] grant,” she said, noting that the grant program was created to support projects that venture into unexplored scientific territory. Gross also praised UCSF for creating an environment where scientists from different departments can join forces and collaborate. In addition to herself and Krogan, Jonathan Weissman, PhD, a UCSF professor of cellular and molecular pharmacology, is also taking part in the project. “We’re able to play off what one group is doing and allow other groups to make progress in parallel things,” Gross said. “The atmosphere at UCSF allows us to do that.” Gross’s and Krogan’s project was funded in late September, after the NIH had publicly announced its initial group of 38 grant recipients. That group included two other UCSF researchers: David Sretavan, MD, PhD, a UCSF professor of ophthalmology and physiology, and John Sedat, PhD, a UCSF professor of biochemistry and biophysics.