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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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October 7, 2013

The 2013 Medicine/Physiology Nobel: Traffic

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Posted by Derek

This year's Medicine Nobel is one that's been anticipated for some time. James Rothman of Yale, Randy W. Schekman of Berkeley, and Thomas C. Südhof of Stanford are cited for their fundamental discoveries in vesicular trafficking, and I can't imagine anyone complaining that it wasn't deserved. (The only controversy would be thanks, once again, to the "Rule of Three" in Alfred Nobel's will. Richard Scheller of Genentech has won prizes with Südhof and with Scheller for his work in the same field).
vesicles.png
Here's the Nobel Foundation's scientific summary, and as usual, it's a good one. Vesicles are membrane-enclosed bubbles that bud off from cellular compartments and transport cargo to other parts of the cell (or outside it entirely), where they merge with another membrane and release their contents. There's a lot of cellular machinery involved on both the sending and receiving end, and that's what this year's winners worked out.

As it turns out, there are specific proteins (such as the SNAREs) imbedded in intracellular membranes that work as an addressing system: "tie up the membrane around this point and send the resulting globule on its way", or "stick here and start the membrane fusion process". This sort of thing is going on constantly inside the cell, and the up-to-the-surface-and-out variation is particularly noticeably in neurons, since they're constantly secreting neurotransmitters into the synapse. That latter process turned out to be very closely tied to signals like local calcium levels, which gives it the ability to be turned on and off quickly.

As the Nobel summary shows, a lot of solid cell biology had to be done to unravel all this. Scheckman looked for yeast cells that showed obvious mutations in their vesicle transport and tracked down what proteins had been altered. Rothman started off with a viral infection system that produced a lot of an easily-trackable protein, and once he'd identified others that helped to move it around, he used these as affinity reagents to find what bound to them in turn. This work dovetailed very neatly with the proteins that Scheckman's lab had identified, and suggested (as you'd figure) that this machinery was conserved across many living systems. Südhof then extended this work into the neurotransmitter area, discovering the proteins involved in the timing signals that are so critical in those cells, and demonstrating their function by generating mouse knockout models along the way.

The importance of all these processes to living systems can't be overstated. Eukaryotic cells have to be compartmentalized to function; there's too much going on for everything to be in the same stew pot all at the same time. So a system for "mailing" materials between those regions is vital. And in the same way, cells have to communicate with others, releasing packets of signaling molecules under very tight supervision, and that's done through many of the same mechanisms. You can trace the history of our understanding of these things through years of Nobel awards, and there will surely be more.

Comments (15) + TrackBacks (0) | Category: Biological News | General Scientific News


COMMENTS

1. Obvious question on October 7, 2013 9:49 AM writes...

In the Pipeline readers, who are your predictions for the 2013 Nobel prize in chemistry?

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2. K C Nicolaou on October 7, 2013 10:03 AM writes...

Me, obviously!

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3. Anonymous on October 7, 2013 10:24 AM writes...

Something got scrambled:

Richard Scheller of Genentech has won prizes with Südhof and with Scheller for his work in the same field).

Permalink to Comment

4. newnickname on October 7, 2013 11:04 AM writes...

@1: "2013 Nobel prize in chemistry?" First choice: Akira Fujishima and Kenichi Honda for discovery of the ACTUALLY USEFUL Honda-Fujishima effect. (Honda was born in 1924 but I think he's still alive.) Second choice: Douglas Prasher for cloning and sharing GFP. Corrects an earlier oversight by the Nobel Committee.

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5. Chemjobber on October 7, 2013 11:23 AM writes...

A question for ItP commenters: everyone makes jokes about KCN's Chemistry Nobel envy, but does anyone have direct evidence (anecdotal or otherwise) that he actually desires it?

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6. ROGI on October 7, 2013 11:41 AM writes...

#5, Chemjobber: If you thought you were studly enough to warrant the attention of... let's say Gwyneth Paltro or Alicia Keys, wouldn't you, parenthetically speaking, desire it? (pretend you weren't married).

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7. non scientist on October 7, 2013 4:51 PM writes...

Have there been any actual medicines developed based on this research? Since medicine is in the prize's name, I'm always interested to hear about the medicine/drug connection.

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8. sgcox on October 7, 2013 4:53 PM writes...

#6 It is a punch below the belt but yes, I can see your point.

So can we go back to #1, #4 ? My vote is for SPR methodology.

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9. drug_hunter on October 7, 2013 5:57 PM writes...

Don't know about KC specifically, but Nobel fever is not unheard of. For example, I've heard that EJ Corey got really testy every fall, waiting to find out if he had won. Perhaps a former EJC student can confirm/deny.

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10. David_Pendlebury on October 7, 2013 6:13 PM writes...

Kenichi Honda passed away in 2011.
http://www.japan-acad.go.jp/en/news/2011/030401.html

By the way, Thomson Reuters named Akira Fujishima a Citation Laureate in 2012, for the contribution you mention.

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11. 5-HT on October 7, 2013 6:30 PM writes...

Kudos to Schekman and Rothman. We'll deserved.

Sudhof is an arrogant prick who has published a lot of crap over the years. There were better choices in the synaptic physiology area than him.

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12. Sudhof on October 8, 2013 6:27 AM writes...

@11: Thanks, I agree!

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13. petros on October 8, 2013 6:46 AM writes...

Rumour has it that Salvador Moncada had a significant team devoted to trying to get him one when he was R&D head at Wellcome. After all his former boss John Vane got one.

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14. Anonymous BMS Researcher on October 8, 2013 6:54 AM writes...

The Physics Nobel goes to François Englert and Peter W. Higgs for the eponymous boson, as many had been predicting.

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15. Anonymous on October 8, 2013 7:38 AM writes...

So now Belgium can claim fame to Jean Claude Van Damme *AND* a Nobile Prize!

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