This year’s Nobel Prize in Medicine or Physiology was awarded jointly to three scientists for solving a mystery of how the cell organizes its transport system. One of the laureates is Thomas Südhof. This professor of molecular and cellular physiology was born in Göttingen, Germany in 1955. He obtained a medical degree from the University of Göttingen in 1982. As he performed research for his doctoral degree at the Max-Planck-Institute for Biophysical Sciences under Victor P. Whittaker, a pioneer in neurochemistry, he became interested in neuroscience. In 1983 Thomas Südhof moved to the United States. In order to expand his knowledge of biochemistry and molecular biology he worked as a postdoctoral fellow at the University of Texas Southwestern Medical Center in Dallas. This is where he cloned the gene for the receptor of LDL (low-density lipoprotein), a molecule in the blood that transports cholesterol. Furthermore, through his work the sequence that mediates the regulation of LDL receptor gene expression by cholesterol was identified. 

After a few years he was offered the chance to start his own laboratory at the UT Southwestern. Südhof then began to investigate the presynaptic neuron. What scientists mainly knew about the presynaptic neuron at the time was that calcium ions stimulate the release of neurotransmitters from membrane-bound sacs, called vesicles, into the synapse, in a process that takes less than a millisecond. This release was known to involve fusion of the vesicles with the plasma membrane. However, how such fusion occured, and how it was triggered by calcium was unknown. In the 1990s Südhof searched for calcium sensitive proteins in nerve cells. His work was able to identify molecular machinery that responds to an influx of calcium ions and directs neighboring proteins to rapidly bind to vesicles at the outer membrane of the nerve cell. The zipper opens up and signal substances are thus released. Through Südhof’s discovery it could be explained how temporal precision is achieved and how the contents of vesicles can be released on command. This can lead to better understand of neurodegenerative diseases in the future, says Südhof.

“At this point, my findings are primarily of use in understanding better how the brain works. Maybe some time in future my findings will be useful for understanding diseases as well, especially neurodegenerative diseases, but my work has no immediate application.”

In more recent studies, which were intensified after he moved to Stanford in 2008, Thomas Südhof examined how pre and postsynaptic proteins form physical connections during synapse formation. More specifically, he was able to identify proteins on presynaptic neurons called neurexins and proteins on the postsynaptic neuron called neuroligins and LRRTMs, which come together and bind to each other across the synaptic cleft. The union of neurexin and neuroligin at the synapse is very important for normal brain functions. Any changes in these proteins impair the brain’s chemistry. Mutations in neurexin or neuroligin genes can cause schizophrenia or autism. When introduced into mice, these mutations change the properties of synapses and impair neurotransmission, according to Südhof’s findings. 

Thomas Südhof’s current research aims to clarify how neuroligin and neurexin, as well as other proteins, control synapse formation and synapse function, and how they mediate synapse remodeling during learning or other adaptive changes of the brain. These kinds of studies are important to improve our understanding on how the brain is wired normally and how such wiring becomes impaired in neuropsychiatric diseases. 

After all of his years of research the most fundamental thing that he has come to learn about the human brain is that “complexity and ability are not directly encoded in the genome, but are indirectly specified by specific genes,” he says. Thomas Südhof’s dedication to science lies in the joy of understanding how it all works.

“I love the pleasure of understanding something, of gaining insight into an important process or property – it is simply rewarding for me to contribute to the knowledge base of our world.”

His advice to other young scientists at the beginning of their careers is to stay true to what they find to be essential. “Follow our passions, not fashions. Always focus on what is important and not on what is particularly noteworthy at a time.” 

Thomas C. Südhof
  • Born: 1955, Göttingen, Germany
  • Family: Wife and two children (plus four adult children from a previous marriage). 
  • Position: MD, Professor of molecular and cellular physiology and, by courtesy, of Neurology and of Psychiatry and Behavioral Sciences at Stanford University School of Medicine.
  • Career: Medical Degree University of Göttingen (1982), postdoc University of Texas Southwestern Medical School, started his own laboratory at UT Southwestern (1986), investigator, Howard Hughes Medical Institute (1991), Professor of Molecular and Cellular Physiology, Stanford University (2008).