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The three scientists who shared this year's Nobel Prize in Physiology or Medicine all made discoveries that illuminate how the body's cells communicate.
The research has sweeping implications for our understanding of how nerves in the brain transmit signals, how the immune system attacks pathogens and how hormones, like insulin, get into the bloodstream.
Bioengineers have already harnessed the discoveries to manufacture new vaccines and improve the quality of insulin for diabetics.
The winners include two Americans — James Rothman of Yale University and Randy Schekman of the University of California, Berkeley — and the German-born Thomas Suedhof of Stanford University. Both Schekman and Suedhof are also investigators at the Howard Hughes Medical Institute.
Their discoveries took place over the course of 30 years. The work got its start with a few simple experiments in cells of yeast – the same organism that leavens bread and brews beer.
In the 1970s, biologists already knew that cells weren't just sacks of fluid. Rather, they contain sophisticated highway systems that shuttle material from one compartment to the next. This cargo moves around cells in bubble-like compartments called vesicles.
In a healthy cell, some of these vesicles make their way to the cell's surface, where the material is released outside the cell. That's one way that cells communicate with each other and with organs in the body.
In 1976, Schekman, a new professor at the University of California, Berkeley, had recently found mutant yeast cells that had faulty transport systems. The cargo just piled up at the cell's surface, like cars stuck in a traffic jam.
By figuring out which genes were defective in these yeasts, Schekman discovered dozens of components that built and controlled the cell's transport system.
But there were still many pieces missing. In particular, it wasn't known how a cargo vesicle knows where to go on the cell's surface and then when to dump out its contents.
"Imagine hundreds of thousands of people who are traveling around hundreds of miles of streets. How are they going to find the right way? Where will the bus stop and open its doors so that people can get out?" Nobel committee secretary Goran Hansson said Monday. "There are similar problems in the cell, to find the right way ... and out to the surface of the cell."
Take for instance two neurons in your brain. One neuron communicates with another by secreting neurotransmitters, such as dopamine and serotonin. But a neuron must release the neurotransmitter at a particular place — and at the right time. Otherwise the message will never make it to the second neuron, or the signal will get scrambled.
That's where Rothman and Suedhof's research comes in. In the 1980s and 1990s, Rothman, now 62, figured out that a signal on the vesicle's surface that helps it dock at just the right place on the cell's surface. The process works a bit like a zipper: A protein on the vesicle zips up with another one on the cell's membrane to position the cargo in the correct location.
Then a few years later, Suedhof, who is now 57, identified the trigger mechanism that dumps the neurotransmitter outside the cell at just the right time by unzipping the two proteins.
This transport system has served as the foundation of modern cell biology and neuroscience.
And breakdowns of the process is involved in a vast range of diseases, including Alzheimer's, cystic fibrosis, muscular dystrophies and some autoimmune disorders.