2013 Nobel Prizes
Compiled by Hikmet Geckil
Web. 9 Oct 2013
The Nobel Prize in Physiology or Medicine 2013
The Nobel Prize in Physiology or Medicine 2013 was awarded jointly to James E. Rothman, Randy W. Schekman and Thomas C. Südhof "for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells".
This year’s Nobel Prize in medicine or physiology was awarded for discoveries in ground-breaking research into how cells use vesicles to safely transport proteins and hormones from one compartment to another within cells. Three investigators will share in the $1.25 million prize: James E. Rothman of Yale University, Randy W. Schekman of the University of California at Berkeley, and Thomas C. Südhof at the Stanford University school of medicine.
This vesicle-transport system lies at the heart of nerve cells’ ability to communicate with each other by releasing neurotransmitters like serotonin and dopamine as well as the body’s ability to regulate its blood sugar levels using the insulin hormone. Toxins like botulin and tetanus are deadly because they destroy the vesicle-transporting machinery.
Lots of textbook diagrams over the years have given the impression that cells are like water-filled balloons in which various parts—such as the information-packed nucleus and energy-producing mitochondria—just float around. In fact, the cells are highly compartmentalized—which allows the molecular pathways within the cell to occur more efficiently and in a very well-orchestrated manner. The whole process of moving the raw material—in the form of proteins or hormones—from one part of the cell to another takes place in transport bubbles (vesicles). More specifically, these vesicles consist of a membrane of fatty molecules, which surrounds the proteins or hormone molecules and keeps them from being released at the wrong time or place.
While the vesicles themselves have long been known, figuring out how the transport system worked was no easy task. Starting in the 1970s, Randy Schekman studied yeast cells and found he could create mutant cells in which the vesicles simply piled up in the cell—going nowhere. He then identified the genes responsible for making sure the vesicles formed and got to where they needed to go. Schekman Lab
But that doesn’t explain how these fatty bubbles release their cargo into another compartment. James Rothman started working on that problem in the 1980s. At the time, many researchers thought that the cells needed to be intact in order to study this process, but Rothman actually broke up the cells into fragments and showed that the fusing of a vesicle with the membrane of another cellular compartment could happen even on these fragments. Eventually he isolated proteins found on the outside of the vesicles that attached to other membranes and then opened up the vesicle like a zipper, releasing the contents. Rothman Lab
Intriguingly, vesicles don’t just open up the second they have latched on to the surface of their cellular destination. It was up to Thomas Südhof to find and characterize a calcium-containing sensor that tells the vesicle when to release its cargo. Thomas Südhof Laboratory
>> Budding Vesicles in Living Cells, by James E. Rothman and Leslie Orci, March 1996
>>The Compartmental Organization of the Golgi Apparatus by James E. Rothman, Septembe r1985
>>The Assembly of Cell Membranes by Harvey F. Lodish, James E. Rothman, January 1979
Novick P, Schekman R: Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1979; 76:1858-1862.
Balch WE, Dunphy WG, Braell WA, Rothman JE: Reconstitution of the transport of protein between successive compartments of the Golgi measured by the coupled incorporation of N-acetylglucosamine. Cell 1984; 39:405-416.
Kaiser CA, Schekman R: Distinct sets of SEC genes govern transport vesicle formation and fusion early in the secretory pathway. Cell 1990; 61:723-733.
Perin MS, Fried VA, Mignery GA, Jahn R, Südhof TC: Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature 1990; 345:260-263.
Sollner T, Whiteheart W, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE: SNAP receptor implicated in vesicle targeting and fusion. Nature 1993;
Hata Y, Slaughter CA, Südhof TC: Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. Nature 1993; 366:347-351.
James E. Rothman at a press conference held at Yale University after the announcement of the 2013 Nobel Prize in Physiology or Medicine.
James E. Rothman, third from left, at Yale University after the announcement of the 2013 Nobel Prize in Physiology or Medicine. From left: Robert Alpern, Dean of the Yale School of Medicine, Joy Hirsh, Professor of Psychiatry & Neurobiology, James Rothman and Peter Salovey, President of Yale University.
2013 Nobel Prize in Chemistry
The Nobel Prize in Chemistry 2013 was awarded jointly to Martin Karplus, Michael Levitt and Arieh Warshel "for the development of multiscale models for complex chemical systems".
Chemical reactions occur at lightning speed. In a fraction of a millisecond, electrons jump from one atomic nucleus to the other. Classical chemistry has a hard time keeping up; it is virtually impossible to experimentally map every little step in a chemical process. Computer modeling of complex chemical processes has earned three scientists the 2013 Nobel Prize in chemistry.
The scientists let computers unveil chemical processes, such as a catalyst’s purification of exhaust fumes or the photosynthesis in green leaves. The mysterious and lightning fast chemical reactions that transfer electrons between atoms have been impossible to observe by the naked eye. The three scientists who take home the prize have harnessed the power of computing to simulate those reactions. The models allow scientists to dissect how plants create energy from light, how proteins fold in cells and how chemical processes purify exhaust fumes.
The work of Karplus, Levitt and Warshel is ground-breaking in that they managed to make Newton’s classical physics work side-by-side with the fundamentally different quantum physics. Previously, chemists had to choose to use either or. The strength of classical physics was that calculations were simple and could be used to model really large molecules. Its weakness, it offered no way to simulate chemical reactions. For that purpose, chemists instead had to use quantum physics. But such calculations required enormous computing power and could therefore only be carried out for small molecules.
This year’s Nobel Laureates in chemistry took the best from both worlds and devised methods that use both classical and quantum physics. For instance, in simulations of how a drug couples to its target protein in the body, the computer performs quantum theoretical calculations on those atoms in the target protein that interact with the drug. The rest of the large protein is simulated using less demanding classical physics.
Today the computer is just as important a tool for chemists as the test tube. Simulations are so realistic that they predict the outcome of traditional experiments.
1. S. Lifson and A. Warshel, J. Chem.Phys. 49, 5116, 1968.
2. M. Levitt and S. Lifson, J. Mol. Biol. 46, 269, 1969.
3. A. Warshel and M. Karplus, J. Amer. Chem. Soc. 94, 5612, 1972.
4. A. Warshel and M. Levitt, J. Mol. Biol. 103, 227, 1976.
5. M. Levitt and A. Warshel, Nature 253, 694, 1975.
6. M. Levitt, J. Mol. Biol. 104, 59, 1976.
7. S. Mukherjee and A. Warshel, PNAS 109, 14881, 2012.
8. Levitt, M. (2001) The birth of computational structural biology, Nature structural biology 8:392–393.
9. Karplus, M. (2006) Spinach on the Ceiling: A Theoretical Chemist’s Return to Biology,Annu. Rev. Biophys. Biomol. Struct. 35: 1–47.