And The Winners Are…

Well it’s the time of year we’ve all been waiting for. That’s right ladies and gentlemen, it’s time to name the winners of the Nobel Prize in Physiology or Medicine! Who needs the Emmys or the Oscars when you’ve got big names like Barbara McClintock and her discovery of genetic recombination or Earl Sutherland Jr. and his work with epinephrine and cyclic AMP signaling? Nobody, that’s who. So who gets to take home the Nobel this year? That would be James E. Rothman, Randy W. Schekman, and Thomas C. Südhof, for their groundbreaking work with vesicle mechanics, both within cells and between cells.

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From left to right: Nobel laureates Randy W. Schekman, Thomas C. Sudhof, James E. Rothman (Source: http://www.nytimes.com)

Each of the three honorees’ research helped to reveal how these vital little organelles function in a wide variety of processes, from neurotransmitter signaling to the genetics of intracellular transport. Vesicles are like little bubbles within cells that contain some chemical or protein and move it from one place to another. When Rothman, Scheckman, and Südhof did their respective work, this role as a key part of transport was already well-known. The question for them was how did vesicles manage to keep a cell functioning so precisely, with such pitch-perfect movement?

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Basic structure of a vesicle (Source: en.wikipedia.org)

Schekman used a dysfunctional system to expose the genetic basis of vesicle transport. He examined yeast, a widely studied organism, when its cellular transport system ran amok. By looking at those cells where vesicles were unable to move correctly (identified by the inevitable traffic jam caused by a broken transport system), he was able to describe three groups of genes that helped to regulate all the smaller processes which guide vesicles safely across the cell’s jumbled inner landscape. These 50 genes encode the varying parts of the route which involves the packaging of proteins within vesicles, their correct movement throughout the cell, and their eventual use at the target site. According to Schekman, one of the most important genes he discovered was the SEC61 gene, which encodes the very beginning of the pathway a protein follows that leads to being secreted from the cell. When this gene is mutated, these proteins never even begin their already complex journey to the outside.

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Randy Schekman pictured alongside a diagram of his research with vesicles in yeast (Source: AFP, Jonathan Nackstrand)

Rothman examined how vesicles interact with cellular membranes when docking on the outside of the cell. His research found that a pair of complementary proteins, one on the surface of the vesicle and one on the target membrane, interlock like a zipper and allow the vesicle to release its cargo by fusing with the cell’s membrane. He also worked to discover how many of these protein pairs existed. By cataloging their remarkable diversity, he was able to explain how the cell managed such a complex web of transportation so efficiently and effectively. His work had remarkable overlap with Schekman’s, as many of the genes found to be involved in coding for these proteins were also present in Schekman’s yeast. This overlap led to the two being awarded the Albert Lasker Award for Basic Medical Research back in 2002.Image

James Rothman and his research on vesicle-membrane fusion (Source: http://www.theguardian.com)

Südhof’s research looked at how brain cells communicate. It was already known that neurotransmitters, the chemicals that allow for neurological messages to be passed between cells, were released from the cell by vesicles as they fused with the cell’s membrane. Südhof wanted to find out how these vesicles knew when to drop their cargo off, that is, how vesicles were able to be sensitive to nerve signals. What he found was a system of cellular machinery that was very sensitive to calcium ions. As these ions flooded into the cell (a significant part of most nerve signaling) these sensitive proteins would trigger other membrane proteins to bind vesicles, thus releasing the necessary neurotransmitters from the cell. His work explained how the contents of vesicles could be released on command and how systems of communication between cells could interact with those systems of transport within cells.

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Südhof’s neurotransmitter vesicle signaling (Source: http://www.nobelprize.org)

As a student of biology, I learned a lot about vesicles over four years. They are pretty fundamental to cellular mechanics, being functional in everything from neurotransmission to immune responses to the everyday cleaning up of broken parts of our cells. These researchers’ collective work, as broad as its goals may seem (not being concerned with fighting a specific disease or fixing a specific problem), has had an immense impact on the way that we understand our bodies. These systems of transportation and communication are pivotal to our ability to combat and cure a wide variety of diseases, ranging from neurological disorders to diabetes. Who would’ve thought a bunch of little sacs would be such a big deal?

Nobel Announcement: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2013/press.html

Some fun facts about the prize in medicine and physiology: http://www.nobelprize.org/nobel_prizes/facts/medicine/index.html

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