UCSF protein researcher wins NIH's Early Independence Award

James Fraser, PhD, a protein researcher who studies structural biology at the California Institute for Quantitative Biosciences (QB3) at the University of California, San Francisco (UCSF), is one of 10 recipients of a prestigious award for young scientists given for the first time by the National Institutes of Health.

Fraser, 29, a QB3 fellow at the UCSF Department of Cellular and Molecular Pharmacology, will receive $1.25 million in direct support for his laboratory for five years. The award, given by the NIH director, will support Fraser's work in deciphering complex mutations in proteins and could lead to better understanding of a broad array of genetic diseases.

Fraser spent four years as a graduate student working in the lab of Tom Alber, a professor of biochemistry and molecular biology at UC Berkeley. There, he helped develop methods to look at the molecular structure of proteins that allowed to understand how the movement of enzymes influenced their rate of reactions. Alber's lab is now using these methods to probe the development of drug resistance among people infected with human immunodeficiency virus, or HIV.

"He's one of the best students I've had, very original, talented and creative," Alber said of his former student. "The methods he and other developed define a whole new way to use structural X-ray crystallography to analyze molecular structure. This has vast application in research and drug discovery.''

In his own lab, in Byers Hall on UCSF's Mission Bay campus, Fraser and his colleagues use computational and biophysical methods to discern how molecules that bind to enzymes at sites distant from their active site can affect that enzyme's behavior. They also study how protein interactions are reshaped during evolution.

Applying these concepts, Fraser will now study how mutations in proteins can cause disease.

"We don't really understand how most point mutations in proteins cause disease,'' Fraser said. "A lot of what we've been describing as causal is really just a symptom. We hope to use the tools I developed in Tom's lab and new collaborations I've established at UCSF to understand the real mechanisms that are causing these diseases.''

While Fraser's team won't initially focus on any one disease during the grant period, "the fundamental lessons should apply to any disease that is caused by point mutations in proteins, which is most genetic disease.''

The Early Independence Awards are part of an NIH effort to support investigators early in their careers to allow qualified young scientists to leapfrog over the traditional post-doctoral training period. The first group of awardees includes 10 exceptional junior investigators. NIH plans to commit approximately $19.3 million to support their research projects over a five-year period.

"The Early Independence Award enables outstanding investigators to establish their independent research careers as soon as possible," said NIH Director Francis S. Collins, M.D., Ph.D. "These Early Independence Award recipients have demonstrated exceptional scientific creativity and productivity."