Medicine Nobel winners show vesicle bubbles in cells key for cargo transport

On Oct. 7, the 2013 Nobel Prize in Physiology or Medicine was awarded jointly to James E. Rothman, Randy W. Schekman and Thomas C. Südhof for their work on transportation mechanisms within the cell. Together, their research highlighted how vesicles, which are bubbles in the cell that contain molecules essential to the organism, transport their cargo. Previously, researchers had been puzzled by how vesicles know where to go and at what time. Thus, the discoveries of Rothman, Schekman and Südhof are a major step in understanding cell communication.

Upon receiving his Ph.D. from Stanford in 1974, Schekman studied yeast cells with malfunctioning transport systems. The vesicles in these cells built up significantly, creating an enormous traffic jam. The American researcher noticed that the malfunctions stemmed from genetic mutations, and, by comparison with the genome of healthy yeast cells, determined what the mutations were in the yeast’s DNA sequence. By doing so, Schekman found the sequence that was responsible for expressing important machinery in the transport system.

Rothman received his Ph.D. from Harvard Medical School in 1976. Focusing more on the mechanism of transport, he discovered how vesicles arrive at the correct locations for their cargo. Without such a mechanism, vesicles would release molecules far from the target locations, completely undermining the point of having a transport system. In addition, essential molecules, such as hormones or insulin, would be unable to arrive at their required positions, leading to undesirable phenotypes.

Rothman found that, to ensure vesicles arrive at the proper place, vesicle surfaces house proteins that bind to the target destination, where the cargo is then released. The combination of proteins is extremely specific, so vesicles will only bind at particular targets with the exact correlating group of proteins, much like a lock and key. This discovery also confirms Schekman’s finding since the surface proteins have been found to be coded by Schekman’s transport system DNA sequence.

Hailing from abroad, Südhof was awarded his Ph.D. in 1982 from Georg-August-Universität. Südhof studied signaling and tackled the question of how vesicles know when to release time-based cargo. The timing of release must be highly regulated or else the cell will be chaotically releasing various molecules at random times.

For instance, without regulation, the vesicle would constantly release neurotransmitters into the cell’s exterior, causing muscle cells to contract and the organism to undergo continuous spastic movement. Südhof found that nerve cells consist of proteins that are sensitive to calcium ion concentration. When there is a net flux of calcium ions going in the cell, these proteins signal the vesicles to bind and release neurotransmitters at the cell surface.

The trio’s contributions to physiology have a major impact on transport system research. Genentech, a large biotechnology company, is currently using the knowledge to optimize the secretion of insulin from engineered yeast cells. For example, with the insight provided by these researchers on transport system mechanisms, employees may mutate cells so its vesicles release molecules like insulin at a higher rate. The collected insulin can be employed to control diabetes.

The 2013 Nobel Prize in Physiology or Medicine, one of world’s renowned and prestigious accolades, was certainly a well-merited award for the three researchers. Their work offers a better understanding of transport systems in the cell, providing a radical breakthrough in physiology. New technology incorporating their discoveries is already being developed for medicine. Thanks to their contributions on transport machinery, cures for diseases caused by secretion issues, such as diabetes and Alzheimer’s, may be found.