NIMH Grantee Receives 2013 Nobel Prize

October 17, 2013 • Science Update

Congratulations to current NIMH grantee Thomas C. Südhof, M.D., at Stanford University School of Medicine, for winning the Nobel Prize in Physiology or Medicine  for his work on how the brain sends and receives chemical messages.

“We are extremely proud of Dr. Südhof,” said National Institute of Mental Health (NIMH) Director Thomas Insel, M.D. “NIMH has supported Dr. Südhof's ground-breaking research for more than two decades as part of our commitment to understanding the fundamental mechanisms of brain function."

The human brain houses about 100 billion neurons—about half the number of stars in the Milky Way. Each of these neurons “converses” with, on average, thousands of other neurons, sending molecular messages in a matter of milliseconds, about the same timeframe as a camera flash. How these messages are sent in such a rapid and precise manner has long been a mystery to neuroscientists. When these messages go awry, mental disorders such as schizophrenia, autism, and depression may arise.

Specifically, Dr. Südhof parsed the proteins that are used in a synapse—the gap between neurons where one neuron reaches out to talk to another via chemical messengers known as neurotransmitters. These specialized spaces are comprised of three components: the messenger or presynaptic neuron, the recipient or postsynaptic neuron, and the cleft or space between these two neurons. Dr. Südhof’s work identified key molecules involved in the rapid release of neurotransmitters from the terminals of presynaptic neurons and revealed how electrical signals in the form of calcium ions instruct a protein called synaptotagmin. Once calcium binds to synaptotagmin, the protein serves as a switch for neurotransmitter-carrying cellular shuttles called vesicles to fuse with the outer surface of the presynaptic neuron and release these chemical messengers into the synaptic cleft. Upon release, the neurotransmitters cross the synaptic cleft and bind to docking sites or receptors on the postsynaptic neuron, triggering an electrical signal to pulse through it. Südhof’s work revealed that synaptotagmins also act as universal calcium sensors in non-neuronal cells, functioning, for example, in the release of hormones such as insulin from pancreatic beta cells.

Dr. Südhof shares the world’s most prestigious science award with James E. Rothman, Ph.D., at Yale University, and Randy W. Schekman, Ph.D., at the University of California, Berkeley. Dr. Rothman unraveled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. Dr. Schekman discovered a set of genes that were required for vesicle traffic. The researchers will share a prize that totals roughly $1.2 million USD.

Previously, Dr. Südhof and Richard H. Scheller, Ph.D., at Genentech, collected the 2013 Albert Lasker Basic Medical Research Award for their work. Known as “America’s Nobels,” the Lasker Awards often predict future Nobel Prize recipients.

The National Institutes of Health (NIH) has supported Dr. Südhof’s research over the past 22 years. In turn, Dr. Südhof has served on several study sections at the NIH Center for Scientific Review, in addition to the Molecular, Cellular, and Developmental Neuroscience study section at NIMH. Over the years, Dr. Südhof’s work on the neurotransmitter release machinery has been supported with research program grants as well as center grants from NIMH. He is also the recipient of an NIMH MERIT (Method to Extend Research in Time) award , which along with an additional NIMH grant  and funding from the Howard Hughes Medical Institute helped support his Nobel work. MERIT awards provide up to 10 years of stable research support for highly productive outstanding investigators working on projects well aligned with the mission of NIMH.

Dr. Südof also holds an NIH TR01 award for work to facilitate the creation of neurons from non-neuronal cells (skin fibroblasts of human patients). This work is anticipated to provide a novel way for scientists to study the biological effects of gene mutations associated with neuropsychiatric diseases.