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Stanford's Sudhof shares Nobel-winning work

Synaptic trafficking could have implications in neurological disorders

Stanford University Professor of molecular and cellular physiology Thomas Sudhof, won the 2013 Nobel Prize in Physiology or Medicine for his research on how brain cells communicate.

Sudhof, 57, shares the prize with James Rothman, Ph.D., a former Stanford professor of biochemistry who now works at Yale University, and Randy Schekman, Ph.D., who did his doctoral work at Stanford and now works at the University of California, Berkeley.

Reached by cellphone in Spain, Sudhof said that as a scientist, he had always dreamed of winning the Nobel Prize.

"… I never imagined I could get one," he said. "I am honored beyond words. I was stunned and literally speechless."

The 2013 Nobel Prize acknowledges the individual contributions of the three scientists to the body of research identifying the biochemical mechanisms by which brain cells, called neurons, bridge a physical gap to communicate information from one cell to another.

Neurons do not physically touch one another but are instead separated by physical gaps called synapses. Communication across synapses happens because of the function of special parts of neuronal cell walls, called synaptic trafficking proteins.

Synaptic trafficking proteins enclose around other molecules, enabling them to be released for travel to a second neuron.

Sudhof's research focused on the attachment of synaptic trafficking proteins to neuronal cell walls.

Knowing how the brain wires itself could help determine how and why connections become dysfunctional, which instead has implications for treating brain diseases such as mental health disorders, Parkinson's Disease and Alzheimer's Disease.

"The best chance we have is to try and counteract the loss of synapses," Sudhof said. "We need to identify a point along a pathway where we can use drugs or activate a pathway to counteract the developments [of the disease. I think we can do it, but at the same time it is a really difficult problem and a large amount of work must be done."

The large amount of research that remains to be done is, in part, because of the massive scale and complexity of the brain. More than 80 billion neurons make up the human brain, and each one connects to thousands of others. These synaptic connections form networks that control all functions of the body, from respiration to behavior and thought.

Sudhof's research shows that even single synapses are complicated.

"A synapse is not just a relay station. It is not even like a computer chip, which is an immutable element. Every synapse is like a nanocomputer all by itself," he stated in a release.

The entire brain is often compared to a complex computer. Modeling brain function is an active area of research, and Sudhof said he believes simulating portions of what the brain does is possible.

"I am not sure about simulating the whole brain with computers. To be honest, I am not even sure that is a particularly important goal right now," he said. "My hopes and feelings of success would be much easier to satisfy: if we could find a pathway that causes synapse loss in disease. Maybe we should be a little more humble towards the enormous wonderful organ that is the brain."

Sudhof said he is very optimistic about the possibilities of future work translating into treatment, in spite of the hugeness of the research questions.

"I think we can do it," he said, "but at the same time, it is a really difficult problem."

Because of deep cuts to federal funding for science and medical research that predate the current government shutdown and sequester of March 2013, Sudhof said he worries about whether it will be even possible to conduct necessary research.

"I think (federal) funding is endangered," he said. "I'm not sure it's there to be honest," Sudhof explained about the effects of cumulative funding cuts to the NIH budget.

"In general, the value of science is being heavily discussed in the U.S. It worries me tremendously. In my view … science is the search for truth," continued Sudhof. "It seems to me that there is a significantly increasingly vocal population that thinks we should not go after truth. That it is not important. That worries … me. The amount of money is not important. What is important is the discussion in the U.S. and worldwide of the importance of true, unbiased, information."

Sudhof lives in Menlo Park with his wife, also a scientist, and two children.

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