Nobel Prizewinners: Physiology or Medicine

Our series on 2013's Nobel prizewinners concludes with the work of Thomas Südhof, Randy Schekman and James Rothman on cell delivery systems. Elizabeth Finkel reports.

Thomas Südhof of Stanford University.

It’s awe-inspiring when nature and mankind hit on the same solution to a problem. This year’s Nobel Prize winners for Physiology or Medicine, Thomas Südhof of Stanford University, Randy Schekman of the University of California, Berkeley and James Rothman of Yale University revealed just such a convergence.

If you want to send a parcel from Melbourne to Boston, you need to package and address it, then take it to the post office for it to be shipped via various carriers to arrive at the precise street and house number. A cell also needs to send cargo to different places. It may be the insulin produced by the cells of the pancreas, or the neurotransmitters that send signals from one nerve cell to the next.

James Rothman of Yale University.

In these cases, the cargo is delivered with precision using a mechanism stunningly similar to the postal system. The cellular cargo is often despatched to a “post office” called the Golgi apparatus, which is found in most cells. From here it is bundled into membrane-wrapped parcels and addressed with so-called SNARE proteins. The curious thing is that once the parcels reach their target, their membranes melt into those of the receiving compartment, spewing their contents into it. Scientists had seen evidence of the cell’s delivery system ever since Camillo Golgi peered through his microscope in 1898 and identified the complex of canal-like structures and tiny parcels (vesicles) that now bear his name. But just how the system operated required the intersection of the three researchers’ efforts over two decades.

Randy Schekman of the University of California, Berkeley

From the late 1970s, Rothman tracked cargo inside cells using a virus like a transponder (viruses hitch a ride on the same service). Schekman tried the time-honoured approach of breaking the system to see how it works. He looked for mutant yeast cells with a dysfunctional delivery system and identified which genes had gone awry. In the 1980s Südhof studied how nerve cell vesicles, triggered by calcium, fused at precise locations on nerve terminals in the space of a few hundred microseconds.

“A great moment came in the early 1990s when they realised they were all studying variations on a theme,” neuroscientist Tom Schwarz at Harvard Medical School explains. These three strands converged, as the researchers realised they were all studying members of the SNARE complex and the proteins that controlled it.

The study has been crucial for understanding diseases where the system fails, such as diabetes and neurodegenerative diseases such as Alzheimer’s.

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