October 22, 2014

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Scientists share win for work on cells

Lisa M. Krieger | San Jose Mercury News

Scientists Dr. Thomas Sudhof of Stanford and Randy Schekman of the University of California Berkeley have won the 2013 Nobel Prize in Medicine, shared with James Rothman from Yale University.

The three scientists, working independently, solved the mystery of how a cell organizes its internal transportation system, controlling the creation and release of important hormones and enzymes. They discovered the principals that govern how this cellular cargo is delivered to right place at the right time.

This trafficking system is so critical that errors in the machinery lead to neurological diseases, diabetes, immunological disorders and ultimately death. Their insights have led directly to the success of the biotechnology industry, which enlists yeast to release useful protein drugs, such as insulin and human growth hormone.

In a Monday morning statement, the 50-member Nobel Assembly lauded Rothman, Schekman and Sudhof for making known “the exquisitely precise control system for the transport and delivery of cellular cargo.” They will share the $1.25 million prize.

Awakened at his El Cerrito, Calif., home with the good news at 1:30 a.m., “My first reaction was, “Oh, my god!” Schekman told UC Berkeley spokesman Robert Sanders. “That was also my second reaction.”

Sudhof heard the news while traveling in Spain for a conference.

Sudhof, 57, is molecular and cellular physiology professor at Stanford. Schekman, 64, is professor of molecular and cell biology at UC-Berkeley. Rothman, 62, is professor of biomedical sciences at Yale University.

Each scientist contributed a key part to the discoveries, according to the Nobel committee.

Schekman decoded a set of genes that were required for the traffic of this cargo in tiny bubbles of fluid called vesicles, which ferry molecules around the cell interior. Rothman unraveled protein machinery that allows the vesicles to fuse with their targets to permit transfer of cargo. The two men worked “collaboratively and competitively” over the years, using different approaches to uncover the same pathway with the same molecules, Schekman told UC Berkeley Media Center.

Sudhof revealed how cellular signals instruct vesicles to release their cargo with precision.

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 cellular traffic system in yeast, according UC Berkeley Media Center.

In the ensuing years, Schekman 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.

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 two decades Schekman consulted for the company.

Sudhof has spent the past 30 years prying loose the secrets of the synapse, the junction where nerve cells communicate with one another in the brain, according to Stanford News Service. The signaling molecules, called neurotransmitters, are released from vesicles that fuse with the outer membrane of nerve cells by using the machinery discovered by Rothman and Schekman.

The firing patterns of our synapses underwrite our consciousness, emotions and behavior. “The computing power of a human or animal brain is much, much higher than that of any computer,” Sudhof told the Stanford News Service. “A synapse is not just a relay station. It is not even like a computer chip…Every synapse is like a nanocomputer all by itself. The amount of neurotransmitter released, or even whether that release occurs at all, depends on that particular synapse’s previous experience.”

Now his laboratory at Stanford studies how malfunctioning signals in the brain may contribute to disease such as Alzheimer’s and autism.

The Nobel prizes, which award achievements in physics, chemistry, medicine, peace and literature, were established in the will of Alfred Nobel, the Swedish inventor of dynamite, who died in 1896. An economics prize was created almost seven decades later in memory of Nobel by the Swedish central bank.

The 2013 Nobel Prize in physics will be announced on today and the chemistry award is set for Wednesday. The Swedish Academy will reveal its choice for the Nobel literature award on Thursday and a Norwegian committee will name the winner or winners of the Nobel Peace Prize on Friday. That award is always announced in Oslo, in line with the wishes of prize founder Alfred Nobel. This year’s Nobel season ends with the economics award on Oct. 14.