Nobels 2013: Physiology or Medicine

Posted by Daniel Cressey

The 2013 Nobel Prize in Physiology or Medicine has been awarded to James Rothman, Randy Schekman and Thomas Südhof.

The three take the prize for “their discoveries of machinery regulating vesicle traffic, a major transport system in our cells”, the Nobel Assembly says. Vesicles are structures that can transport molecules around cells and deliver them to where they are required.

Schekman, of the University of California, Berkeley, identified genes essential to vesicle traffic, and Rothman, of Yale University in New Haven, Connecticut, worked out how vesicles transfer their cargo. Südhof, now based at Stanford University in California, finished the picture by detailing how vesicles are signalled to release their cargo, the prize committee reports.

“Through their discoveries, Rothman, Schekman and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes and immunological disorders,” says the Nobel statement on the award.

Rothman and Schekman previously won the 2002 Lasker Prize for their work in membrane trafficking. In 2010 Südhof and Rothman shared a Kavli prize with Richard Scheller of the biotechnology company Genentech for work on signalling between brain cells.

The award is “long overdue”, says Bill Wickner, a molecular biologist at Dartmouth University in Hanover, New Hampshire. “I heard from Randy [Schekman]. He was happily in shock, but delighted.” Wickner says that the award “reflects a fundamental problem of cell biology that was approached by these investigator in three very different ways”. Schekman screened mutated strains of yeast and identified dozens of proteins involved in vesicle trafficking. Rothman, meanwhile, used cell extracts to identify proteins needed for membrane vesicles to fuse.

All three laureates are previous winners of the Lasker award, which is sometimes called the mini-Nobel. Südhof won it last year (with Richard Scheller) for their work on the release of neurotransmitters. Schekman and Rothman shared the award in 2002.

Hidde Ploegh, an immunologist at the Whitehead Institute in Cambridge, Massachusetts, says that the trio’s work is so fundamental to cell biology that it’s easy to take it for granted. “This is the stuff when we teach cell biology to biology majors and graduate students, many aspects of vesicular transport are presented as if it’s been there all long.”

Nature has published a number of the key papers, cited by the Nobel Comittee:

“Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C.”

“SNAP receptor implicated in vesicle targeting and fusion.”

“Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin.”

Our sister journal Nature Medicine will soon publish an essay (PDF here) by Südhof to commemorate his Lasker award:  “Our work, together with that of other researchers, uncovered a plausible mechanism explaining how membranes undergo rapid fusion during transmitter release, how such fusion is regulated by calcium and how the calcium-controlled fusion of synaptic vesicles is spatially organized in the presynaptic terminal. Nevertheless, many new questions now arise that are not just details but of great importance. For example, what are the precise physicochemical mechanisms underlying fusion, and what is the role of the fusion mechanism we outlined in brain diseases? Much remains to be done in this field.”

Rothman (PDF here) and Schekman (PDF here) have their own Nature Medicine essays.

With additional reporting by Ewen Callaway./Nature