CA, Yale researchers win Nobel in Medicine

Randy W. Schekman, professor of molecular and cell biology at the University of California, Berkeley, has won the 2013 Nobel Prize in Physiology or Medicine for his role in revealing the machinery that regulates the  transport and secretion of proteins in our cells. He shares the prize with James E. Rothman of Yale University and Thomas C. Südhof of Stanford University.

Discoveries by Schekman on how yeast secrete proteins led directly to the success of the biotechnology industry, which was able to coax yeast to release useful protein drugs, such as insulin and human growth hormone. The three scientists’ research on protein transport in cells, and how cells control this trafficking to secrete hormones and enzymes, illuminated the workings of a fundamental process in cell physiology.

In a statement, the 50-member Nobel Assembly lauded Rothman, Schekman and Südhof for making known “the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders.”

“My first reaction was, “Oh, my god!” said Schekman, 64, who was awakened at his El Cerrito home with the good news at 1:30 a.m. “That was also my second reaction.”

Schekman and Rothman separately mapped out one of the body’s critical networks, the system in all cells that shuttles hormones and enzymes out and adds to the cell surface so it can grow and divide. The system, which utilizes little membrane bubbles to ferry molecules around the cell interior, is so critical that errors in the machinery inevitably lead to death.

“Ten percent of the proteins that cells make are secreted, including growth factors and hormones, neurotransmitters by nerve cells and insulin from pancreas cells,” said Schekman, a Howard Hughes Medical Institute Investigator.

In what some thought was a foolish decision, Schekman decided in 1976, when he first joined the College of Letters & Science at UC Berkeley, to explore this system in yeast. In the ensuing years, he mapped out the machinery by which yeast cells sort, package and deliver proteins via membrane bubbles to the cell surface, secreting proteins important in yeast communication and in mating. Yeast also use the process to deliver receptors to the surface, the cells’ main way of controlling activities such as the intake of nutrients like glucose.

In the 1980s and 90s, these findings enabled the biotechnology industry to exploit the secretion system in yeast to create and spit out pharmaceutical products and industrial enzymes. Today, diabetics worldwide use insulin produced and secreted by yeast, and most of the hepatitis B vaccine used around the world is secreted by yeast. Both systems were developed by Chiron Corp. of Emeryville, Calif., now part of Novartis International AG, during the 20 years Schekman consulted for the company.

Various diseases, including some forms of diabetes and a form of hemophilia, involve a hitch in the secretion system of cells, and Schekman is now investigating a possible link to Alzheimer’s disease.

“Our findings have aided people in understanding these diseases,” said Schekman.

Based on the machinery discovered by Schekman and Rothman, Südhof subsequently discovered how nerve cells release signaling molecules, called neurotransmitters, to communicate.

For his contributions, he was elected to the National Academy of Sciences in 1992, received the Gairdner International Award in 1996 and the Lasker Award for basic and clinical research in 2002. He was elected president of the American Society for Cell Biology in 1999. On Oct. 3, Schekman received the Otto Warburg Medal of the German Society for Biochemistry and Molecular Biology, which is considered the highest German award in the fields of biochemistry and molecular biology.

Schekman, formerly editor of the journal Proceedings of the National Academy of Sciences, currently is editor-in-chief of the new open access journal eLife.

Schekman lives with his wife, Nancy Walls, in El Cerrito, Calif. They have two children, a son, Joel, and a daughter, Lauren.


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