- Person
- James Rothman
- Lived
- b. 1950
- Field
- Cell biology, biochemistry
- From
- American
The story
James Rothman, the son of a Jewish small-town paediatrician in Haverhill, Massachusetts, set out to be a theoretical physicist. At Yale his father persuaded him to try biology, and as a first-year student at Harvard Medical School he learned that cells move their products around in tiny membrane bubbles called vesicles. How each vesicle found the right destination and emptied its cargo there was a complete mystery. It became his life’s work.
At Stanford University from 1978, Rothman took an unusual approach. Instead of watching whole cells, he tried to reproduce vesicle transport in a test tube, using broken-open cells, so that every ingredient could be isolated and identified. In 1984 his laboratory reported that it had done so for the Golgi apparatus, the cell’s packaging centre. Using this system, his team purified the proteins that make vesicles fuse: first a protein called NSF, then its partners, the SNAPs, and in 1993 the receptors they act on, which Rothman named SNAREs.
SNAREs work like a zipper. One half sits on the vesicle and the matching half on the target membrane. When the right pair meet, they wind tightly together and pull the membranes into contact so that they merge and the cargo is released. Because each SNARE pairs only with particular partners, the system also acts as an address label, ensuring delivery to the right place. Some of the genes that Randy Schekman had discovered in yeast turned out to encode the same machinery, revealing an ancient system shared by all complex life. Rothman, Schekman and Thomas Südhof shared the 2013 Nobel Prize in Physiology or Medicine.
The discovery explains processes vital to health. Insulin is released from the pancreas, and messages are passed between nerve cells, by vesicles fusing through SNAREs, and the Nobel committee noted that faulty vesicle transport contributes to diabetes and to neurological and immune disorders. It also explained how botulinum toxin works: it cuts SNARE proteins in nerve endings, blocking the release of the signal that makes muscles contract. That is the basis of both the paralysis of botulism and the medical use of tiny doses of the toxin to treat muscle spasms and chronic migraine.
Why it matters
Rothman’s SNARE machinery underpins today’s understanding of insulin release, nerve signalling and toxins such as botulinum, guiding research on diabetes and brain disorders.
About James Rothman
Physicist-turned-biochemist who discovered how cells package and deliver molecules in vesicles, the machinery behind insulin release and nerve signals, and the target of botulinum and tetanus toxins.
Sources
- Press release: The Nobel Prize in Physiology or Medicine 2013 NobelPrize.org
- James E. Rothman, Biographical NobelPrize.org
- Association of Botulinum Neurotoxin Serotype A Light Chain with Plasma Membrane-bound SNAP-25 Journal of Biological Chemistry (PubMed Central)
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.