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A Nobel Prize for studies of cell trafficking

As he neared the end of the day in October that began with an early-morning phone call from Sweden, James E. Rothman, Ph.D., recalled before a gathering of his colleagues, students, and university leaders what he described as an “out-of-body experience”—the news that he had shared in the 2013 Nobel Prize in physiology or medicine.

“I have gotten close to 1,000 e-mails,” said Rothman, the Fergus F. Wallace Professor of Biomedical Sciences and professor and chair of cell biology, speaking at a reception in the Beinecke Rare Book and Manuscript Library on the evening of October 7. “You hear from all kinds of people: someone who practiced medicine with my father, a third grade classmate.”

Earlier in the day at a press conference he said he was still absorbing the news. “It’s a little hard to believe all this is happening,” he said. Rothman noted his good fortune in having studied at Yale and learning “to appreciate science and intellectual activity at its highest, to have matured and started my career as a researcher when your idea was the only limit. Any risk could be taken, no matter how difficult. I was fortunate to have taken a few of those risks and today’s Nobel Prize recognizes the success that came out of that.”

The prize acknowledged his contributions to the understanding of membrane trafficking, the means by which proteins and other materials are transported within and between cells. Rothman, a 1971 Yale College graduate who previously shared in the Albert Lasker Award for Basic Medical Research, the Louise Gross Horwitz Prize of Columbia University, and the Kavli Prize in Neuroscience, is one of the world’s foremost experts on exocytosis, a form of trafficking in which cargo-bearing spheres called vesicles fuse with cell membranes to deliver their contents.

This process is essential to such processes as cell division and insulin secretion, for example, but also plays a crucial role in the nervous system. Vesicles carrying neurotransmitters fuse with cell membranes at synapses and pass on chemical messages that govern movement, perception, cognition, memory, and mood. For three decades, Rothman has performed experiments that have revealed the molecular machinery of membrane trafficking in fine detail. In much of his work Rothman sidestepped the complexities of working with complete cells by using a “cell-free” approach—isolating the intracellular components crucial to membrane trafficking.

Rothman and the two scientists who shared in the $1.2 million award—Randy W. Schekman, Ph.D., of the University of California−Berkeley, and Thomas Südhof, M.D., of Stanford University—all faced skepticism within the scientific community when they began their research. Each went on to solve a different piece of the puzzle.

While Rothman figured out the machinery under-lying membrane trafficking, Schekman discovered a set of genes essential for vesicle traffic, and Südhof determined how vesicles know when and where to release their cargo.

Rothman began his research career after receiving his Ph.D. from Harvard in 1976. From there he went on to the Massachusetts Institute of Technology, Stanford, Princeton, Memorial Sloan-Kettering, and Columbia before coming to Yale in 2008.

“When Jim started his career, a number of successful biochemists were recognizing the importance of studying molecular processes in cell-free systems, but no one imagined that you could study vesicle trafficking in a cell-free system,” said Robert J. Alpern, M.D., dean and Ensign Professor of Medicine, at the press conference. This bold approach revolutionized the field.”

“Yale is absolutely thrilled to have one of our most distinguished faculty—who is also one of our most distinguished alumni—receive this great honor,” said President Peter Salovey, Ph.D., the Chris Argyris Professor of Psychology.