Medicine Nobel for solving how cells shuttle molecules

2019-02-28 03:01:05

By Andy Coghlan (Image: TT News Agency/Reuters) Revealing how vital chemicals like insulin are transported within and between cells has earned the Nobel prize in physiology or medicine for two Americans and one German-born researcher. Aside from advancing our knowledge about cells, the work has revealed the mechanisms of many diseases. “We honour three scientists who have solved the mystery of how the cell organises its transport system,” said the chairman of the Nobel committee, Juleen Zierath of the Karolinska Institute, as she announced the prize today at a press conference in Stockholm, Sweden. James Rothman of Yale University in New Haven, Connecticut, Randy Schekman of the University of California, Berkeley, and German-born Thomas Südhof of Stanford University in California, share the 8 million Swedish kronor ($1.2 million) prize. Collectively, they revealed how multitudes of tiny chambers in cells called vesicles pass on their contents, either to other vesicles and compartments within cells or to neighbouring cells. Vesicles work by fusing with the surface of another vesicle within the cell or with cell membranes. At just the right moment, they deliver their contents to where they’re needed next, either to another vesicle or expelled out of the cell to pass a signal to a neighbouring cell. Because the vesicles contain and release vital chemicals such as insulin and neurotransmitters that trigger brain signalling vital for thought, studying defects in such systems can reveal the workings of diseases including diabetes, neurological conditions and immunological disorders. They can also explain how bacteria causing diseases such as typhoid and botulism can kill with toxins that disrupt vesicle transport. Schekman set the ball rolling in the 1970s by developing mutated forms of yeast with faulty vesicle transport. “He created mutants with defective transport machinery, causing pile-ups in certain parts of the cell,” said Zierath. Through trial and error, he discovered three sets of genes that, when mutated, triggered the traffic jams. In the next two decades, Rothman worked out how vesicles in mammalian cells dock and fuse in the right place. He discovered that proteins on one vesicle bind counterparts on target vesicles or membranes to form a kind of molecular zip, capable of releasing the contents on order. “It ensures it fuses at the right destination and releases it in the right place,” said Zierath. In the 1990s, Südhof completed the puzzle by showing in nerve cells how calcium ions give vesicles the order to release their cargo. His discovery revealed how nerve cells release neurotransmitters which carry signals to and within the brain. When this article was first published on 7 October 2013, it mistook Juleen Zierath’s sex. Apologies to her. More on these topics: