Yale's Fergus F. Wallace Professor of Biomedical Sciences James E. Rothman, UC Berkeley's Professor of Molecular and Cell Biology Randy W. Schekman, and Stanford's Professor of Molecular and Cellular Physiology Thomas C. Südhof today were jointly awarded the 2013 Nobel Prize in Physiology or Medicine. The Nobel Assembly at Karolinska Institutet in Stockholm, which awards the prize in physiology or medicine, cited "their discoveries of machinery regulating vesicle traffic, a major transport system in our cells"
The new laureates responded to the announcement in a variety of ways. Professor Rothman was "completely shocked and surprised." Professor Schekman "danced around with my wife and repeatedly said 'oh my god, oh my god'" and Professor Südhof simply said "Are you serious?".
The process of choosing a particular discovery for recognition from among the hordes of truly fine work nominated for the Prize (380 nominations this year) is quite difficult. In the end, the Nobel Assembly is seeking "a discovery that has changed the paradigm in an area of physiology or medicine, one who has changed our understanding of life or the practice of medicine."
The existence of every living cell depends on the production and transport of a huge range of molecules within the cell. Many of these molecules must be exported from the cell, such as insulin, which acts within the blood stream, and neurotransmitters, which function in the synapses between nerve cells. However, most molecules are too large to pass freely through internal or external cellular membranes. To get around this problem, large molecules are packaged within vesicles, in which they are wrapped within small spherical membranes having a structure closely related to that of the cellular membrane.
The newest Nobel Laureates won the prize for sorting out just how vesicles manage the precise timing and location required for delivery of their contents. In the 1970s, Professor Schekman studied the genetic basis for vesicle formation and control. He used yeast cell strains whose genetics produced defective vesicle control, in which vesicles piled up in specific parts of the cell. By identifying the mutated genes, Schekman identified three classes of genes that control the machinery that determines how a cell forms and transports vesicles to maintain its health.
In the 1980s and 1990s, Professor Rothman studied vesicle transport in mammalian cells. He discovered that a particular protein complex provides the machinery that lets vesicles dock and fuse with the membranes for which they are targeted. These vesicle binding proteins only allow a given vesicle to transport its cargo through the right type of membrane – one that has matching proteins embedded in its structure, which ensures that the contents of a vesicle are delivered only to their intended location. The process is controlled by the same genes Schekman had discovered in yeast cells, indicating that vesicle transport has survived the evolutionary process for at least half a billion years.
Professor Südhof is a neuroscientist who is interested in how nerve cells communicate. While it was known that neurotransmitters are released from vesicles as described by Rothman and Schekman, these vesicles only open when a nerve cell communicates with its neighbors. In the 1990s, he decided to study how this very specific behavior was controlled. He identified molecular machinery that triggers the vesicles to bind to a nearby cell membrane when in the presence of calcium ions, thereby explaining how the contents of a vesicle can be liberated by external control.
This year's monetary prize has been set at eight million Swedish kroner, or about $1.25 million US dollars. The prize money is usually split even between multiple Laureates. The Nobel Prize Award Ceremonies will be held in Stockholm on December 10.
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