Fraser appointed to Bowes Biomedical Investigator Program

James Fraser, PhD, has been appointed to the Bowes Biomedical Investigator Program. Fraser studies the shapes and movements of macromolecules, a category of molecules that includes proteins and carbohydrates. Over the course of his career, he has developed several new tools for creating maps of these tiny structures, a critical first step for finding new drugs. As a program investigator, Fraser will receive $1.25 million over the next five years to support his research and teaching.

Program investigators are early- and mid-career UCSF faculty researchers who are chosen based on the quality of their scientific contributions, the significance of their potential impacts, and the novelty of their approaches to discovery. Fraser is a faculty member in the Department of Bioengineering and Therapeutic Sciences, a joint department of the UCSF Schools of Pharmacy and Medicine.

One key step in the drug discovery process involves designing molecules that fit into proteins, like keys in locks. Scientists often use a technique called x-ray crystallography to create a 3-D model of proteins to test how smaller molecules bind to them.

Traditional x-ray crystallography has limitations, however. Some of Fraser’s earliest work showed that the cold temperatures usually required for the technique actually change the behaviors of proteins, which normally function inside of warm, living cells. Fraser developed new ways of doing crystallography over a wide range of temperatures, allowing him to see how molecules move, change, and function in a cell.

It’s the difference between looking at blueprints of the parts that make up a Boeing 747 engine and actually testing how those same parts behave during a flight.

“Using this technique, we’re witnesses not just to static structures, but to moving ensembles,” Fraser said. “At different temperatures, we can finally glimpse nooks and crannies in proteins that might be good targets for new drug therapies.”

Fraser is currently applying the technology to the problem of antibiotic resistance in a research project with Ian Seiple, PhD, a faculty member at the UCSF Cardiovascular Research Institute, who holds a joint appointment in the School of Pharmacy’s Department of Pharmaceutical Chemistry.