Nobel Laureate Rothman advanced cell research at Princeton

Oct. 8, 2013 8 p.m.

The insights into the way cells organize their transport systems that earned James Rothman the 2013 Nobel Prize in Physiology or Medicine on Oct. 7 were built through a career that included advances made during three years on the faculty at Princeton.

Rothman, a professor and chair of the Department of Cell Biology at Yale University, was awarded the prize along with Randy Schekman of the University of California-Berkeley and Thomas Südhof of Stanford University. The Royal Swedish Academy recognized Rothman for unraveling the protein machinery that allows tiny transporters inside cells, known as vesicles, to deliver their cargo within and outside the cell. This process allows cells to secrete insulin into the bloodstream, for example, and neurons to release neurotransmitters.

Frederick Hughson, a professor of molecular biology at Princeton, said work Rothman conducted at Princeton laid the groundwork for his key findings and offered important clues that Rothman was on the right track in his search for the proteins needed for the membrane, or covering, of the vesicle to fuse with its target's membrane, allowing for the vesicle's cargo to be delivered.

The proteins that cause the membrane of the vesicle to fuse with the membrane of its target are called SNAREs, Hughson said, and Rothman's work at Princeton included identifying and purifying other proteins that led directly to the discovery of the SNAREs themselves.

"He used these other proteins as bait to fish the SNAREs out of cell extracts containing thousands of other proteins," Hughson said. "The groundwork for that breakthrough was laid at Princeton."

Also during Rothman's time at Princeton, Hughson said, it became clear that Rothman and fellow Nobel laureate Schekman had separately identified the same protein as a key driver of cellular transport.

"Schekman was using a genetic approach and Rothman was using a biochemical approach, and they realized it had yielded the same answer," Hughson said. "That was a pivotal moment when it became clear to everyone that both of them were on the right track."

Hughson, whose own research focuses in part on revealing the exact three-dimensional structures of such proteins, first met Rothman when Hughson was a prospective graduate student in the mid 1980s and Rothman was a Stanford professor. Rothman spent an hour and a half with Hughson, drawing on a whiteboard to describe the system of cellular transport and explain how proteins must be involved.

"And almost 30 years later, you could say that almost everything he drew on that white board has come to be understood, much of it through his work," Hughson said.