3 Researchers Win Nobel Prize in Chemistry
Martin Karplus, 83, of the University of Strasbourg in France and Harvard University, Michael Levitt, 66, of Stanford University, and Arieh Warshel, 72, of the University of Southern California, share the honor and the approximately $1.2 million that accompanies it. Their computer programs use the classical laws of motion dating back to Isaac Newton to track the movement of a multitude of atoms and quantum physics to describe the breaking and forming of chemical bonds.
All three winners are naturalized American citizens. Dr. Karplus, born in Austria, is also an Austrian citizen. Dr. Levitt, born in South Africa, also holds British and Israeli citizenships, and Dr. Warshel, born in Israel, is also an Israeli citizen.
The Royal Swedish Academy of Sciences in Stockholm, which awards the prize, cited the three “for the development of multiscale models for complex chemical systems.” As a news release explained it, “Chemists used to create models of molecules using plastic balls and sticks,” but “today the modeling is carried out in computers,” thanks in part to work done in the 1970s by the three new laureates.
Their work has long been supported by federal science grants, said Francis S. Collins, director of the National Institutes of Health, which has had to send home most of its scientists because of the government shutdown. Noting that Monday’s winners of the Nobel Prize in Physiology or Medicine were also underwritten by the N.I.H., Dr. Collins said in an e-mail to a reporter on Wednesday: “The irony continues.”
For Dr. Levitt, the unexpected phone call from Stockholm came at 2:15 in the morning. “It was an enormous shock,” he said, admitting that he had checked various Nobel predictions on the Internet. “You will not find my name on any of them. I’m not sure it was a good thing or a bad thing.”
With committee members he knew personally informing him that he had won, Dr. Levitt realized it was not a hoax.
“One of the members I promised to send a review to maybe a couple of years ago, but I haven’t done it yet,” Dr. Levitt said. “He said, ‘We haven’t gotten your review yet, but we’re still going to give you the prize.’ ”
Dr. Levitt then called his 98-year-old mother in London and told her to turn on the computer and watch the news conference on the Web. She asked him to spell out the Web site — nobelprize.org. Dr. Levitt told her, “Just Google ‘Nobel Prize,’ and it’ll be the first hit.”
In the laboratory, experimental chemists can readily tell the beginning chemical ingredients and the final products. But the actual reactions usually occur very quickly. “It’s like seeing all the actors before Hamlet,” said Sven Lidin, chairman of the Nobel selection committee, during the prize announcement webcast on Wednesday, “and all the dead bodies after, and then you wonder what happened in the middle. And actually there is some interesting action there, and this is what theoretical chemistry provides us with — the whole drama.”
But in the 1960s, when a computer filled a room, computer programs had to be crammed into small slices of memory, limiting what could be done. At the Weizmann Institute of Science in Israel, Dr. Warshel, who was then a doctoral student, and Dr. Levitt, who worked with Dr. Warshel as a computer programmer, calculated the behavior of molecules, even very large biological molecules, although that early work used Newtonian physics and not quantum effects.
Meanwhile, at Harvard, Dr. Karplus’s research group developed computer programs that simulated chemical reactions and employed the full power of quantum physics, which looks at physical reactions at the microscopic level. After completing his doctorate, Dr. Warshel joined Dr. Karplus’s laboratory as a postdoctoral researcher, and in 1972, they published a paper that combined quantum and classical physics in describing the chemical behavior of certain molecules.
Later, Dr. Warshel renewed his collaboration with Dr. Levitt, who had completed his doctorate at the University of Cambridge in England, expanding their programs to tackle enzymes, which are proteins that govern chemical reactions in living organisms. From bouncing X-rays off proteins, chemists knew the shapes of some enzymes, but less about their functions.
“It’s like seeing a watch and wondering how it actually works,” Dr. Warshel said. “So in short, what we developed is a way, which required a computer, to take the structure of a protein and then to eventually understand how exactly it does what it does.”
They found that they could not understand the behavior of the enzyme without including the effects of the surrounding molecules — water, in particular. “This was really, in my view, the conceptual breakthrough,” Dr. Warshel said. “I realized that everything you want to do with computers could be done if you make it simple enough. We wrote in a way that did not require too much memory.”
Experimental scientists were slow to accept the new work, Dr. Warshel said. “When you do something on computer, it’s very easy to dismiss it and say you made it up,” he said. He said the experimentalists were happy when the calculations agreed with the experiments, but not when Dr. Warshel claimed to be describing phenomena not seen in the experiments.
“The last thing people want is that you will come and explain their system,” he said. “I never succeeded to convince anyone. I just made them angry.”
Today, Dr. Lidin of the Nobel committee said, computer simulations have become as informative as the experiments. “You still have to do the experiment,” he said. “But the predictions that theory make are becoming so much powerful these days that we can perhaps save 90 percent of the experimenting and concentrate on the 10 percent where we know that the most important results will lie.”
Lawrence K. Altman contributed reporting.
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Collision Course: It was the longest, most costly manhunt in science for an elusive particle that was said to be key to the workings of the universe. For a generation of physicists, it was an appointment with history.
THE NOBEL PRIZE IN PHYSICS 2013
http://www.nobelprize.org/
http://www.nobelprize.org/nobel_prizes/physics/laureates/2013/popular-physicsprize2013.pdf
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Higgs boson scientists win Nobel prize in physics
By James Morgan
Science reporter, BBC News
The Nobel committee decided Englert and Higgs should jointly take the accolade for the boson, discovered at Cern in 2012
Peter Higgs, from the UK, and Francois Englert from Belgium, shared the prize.
In the 1960s they were among several physicists who proposed a mechanism to explain why the most basic building blocks of the Universe have mass.
The mechanism predicts a particle - the Higgs boson - which was finally discovered in 2012 at the Large Hadron Collider at Cern, in Switzerland.
"I am overwhelmed to receive this award... I would also like to congratulate all those who have contributed to the discovery of this new particle”
'On holiday'
Professor Higgs is renowned for shying away from the limelight, and he could not be located for interview in the immediate aftermath of the announcement.
"He's gone on holiday without a phone to avoid the media storm," his Edinburgh University physics colleague Alan Walker told UK media, adding that Higgs had also been unwell.
But the university released a prepared statement from Higgs, 84, who is an emeritus professor of theoretical physics:
"I am overwhelmed to receive this award and thank the Royal Swedish Academy," he said.
"I would also like to congratulate all those who have contributed to the discovery of this new particle and to thank my family, friends and colleagues for their support.
"I hope this recognition of fundamental science will help raise awareness of the value of blue-sky research."
Francois Englert, 80, said he was "very happy" to win the award, speaking at the ceremony via phone link.
"At first I thought I didn't have it [the prize] because I didn't see the announcement," he told the committee, after their news conference was delayed by more than an hour.
Higgs was born in Newcastle upon Tyne, but it was in Edinburgh in 1964 that he had his big idea - an explanation of why the matter in the Universe has substance, or mass.
His theory involved a missing particle in the Standard Model of physics, which has come to be known as the Higgs boson.
Within weeks, Francois Englert independently published his own, similar theory, alongside his now deceased colleague Robert Brout.
Three other physicists - Gerald Guralnik, Tom Kibble and Carl Hagen - also made key contributions to the theory, and spoke at the announcement of the discovery of the Higgs boson in 2012.
Hagen has long argued for the name of the particle to be changed, protesting at the "rock star" status in which Higgs is held.
And Higgs, too, has expressed his discomfort with the attention he has received, preferring to call the particle "the scalar boson".
In a statement on Tuesday, Kibble, of Imperial College London, said he was "glad" the Nobel Prize had gone to the work of Higgs and Englert.
"My two collaborators, Gerald Guralnik and Carl Hagen, and I contributed to that discovery, but our paper was unquestionably the last of the three to be published.
"It is therefore no surprise that the Swedish Academy felt unable to include us, constrained as they are by a self-imposed rule that the prize cannot be shared by more than three people.
"My sincere congratulations go to the two Prize winners, Francois Englert and Peter Higgs."
International effort
Proving their theory correct took almost half a century and involved creating the biggest and most sophisticated machine humankind has ever built.
The Large Hadron Collider (LHC) at Cern lies in a circular tunnel almost 17 miles round. It's so big it's partly in Switzerland, partly in France. It took 10 years and thousands of scientists and engineers to build it.
Cern director general Rolf Heuer said he was "thrilled" that this year's prize had gone to particle physics.
"The discovery of the Higgs boson at Cern... marks the culmination of decades of intellectual effort by many people around the world," he said.
The Nobel Prizes - which also cover chemistry, medicine, literature, peace and economics - are valued at 10m Swedish Krona. Laureates also receive a medal and a diploma.
The official citation for Englert and Higgs read: "For the theoretical discovery of a mechanism that contributes to our understanding of the origin of mass of subatomic particles, and which recently was confirmed through the discovery of the predicted fundamental particle, by the Atlas and CMS experiments at Cern's Large Hadron Collider".
David Willetts, UK minister for universities and science, said the award was "an incredible endorsement of the quality of UK science".
Prime Minister David Cameron said: "This brilliant achievement is richly deserved recognition of Peter Higgs' lifetime of dedicated research and his passion for science.
"It is also a credit to the world-leading British universities in which this research was carried out.
"It took nearly 50 years and thousands of great minds to discover the Higgs boson after Professor Higgs proposed it, and he and all those people should be extremely proud."
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Press Release
2013-10-07
The Nobel Prize in Physiology or Medicine 2013
James E. Rothman, Randy W. Schekman, Thomas C. Südhof
Press Release
2013-10-07
The Nobel Assembly at Karolinska Institutet has today decided to award the 2013 Nobel Prize in Physiology or Medicine 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.
Summary
The 2013 Nobel Prize honours three scientists who have solved the mystery of how the cell organizes its transport system. Each cell is a factory that produces and exports molecules. For instance, insulin is manufactured and released into the blood and chemical signals called neurotransmitters are sent from one nerve cell to another. These molecules are transported around the cell in small packages called vesicles. The three Nobel Laureates have discovered the molecular principles that govern how this cargo is delivered to the right place at the right time in the cell.
Randy Schekman discovered a set of genes that were required for vesicle traffic. James Rothman unravelled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. Thomas Südhof revealed how signals instruct vesicles to release their cargo with precision.
Through their discoveries, Rothman, Schekman and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders.
How cargo is transported in the cell
In a large and busy port, systems are required to ensure that the correct cargo is shipped to the correct destination at the right time. The cell, with its different compartments called organelles, faces a similar problem: cells produce molecules such as hormones, neurotransmitters, cytokines and enzymes that have to be delivered to other places inside the cell, or exported out of the cell, at exactly the right moment. Timing and location are everything. Miniature bubble-like vesicles, surrounded by membranes, shuttle the cargo between organelles or fuse with the outer membrane of the cell and release their cargo to the outside. This is of major importance, as it triggers nerve activation in the case of transmitter substances, or controls metabolism in the case of hormones. How do these vesicles know where and when to deliver their cargo?
Traffic congestion reveals genetic controllers
Randy Schekman was fascinated by how the cell organizes its transport system and in the 1970s decided to study its genetic basis by using yeast as a model system. In a genetic screen, he identified yeast cells with defective transport machinery, giving rise to a situation resembling a poorly planned public transport system. Vesicles piled up in certain parts of the cell. He found that the cause of this congestion was genetic and went on to identify the mutated genes. Schekman identified three classes of genes that control different facets of the cell´s transport system, thereby providing new insights into the tightly regulated machinery that mediates vesicle transport in the cell.
Docking with precision
James Rothman was also intrigued by the nature of the cell´s transport system. When studying vesicle transport in mammalian cells in the 1980s and 1990s, Rothman discovered that a protein complex enables vesicles to dock and fuse with their target membranes. In the fusion process, proteins on the vesicles and target membranes bind to each other like the two sides of a zipper. The fact that there are many such proteins and that they bind only in specific combinations ensures that cargo is delivered to a precise location. The same principle operates inside the cell and when a vesicle binds to the cell´s outer membrane to release its contents.
It turned out that some of the genes Schekman had discovered in yeast coded for proteins corresponding to those Rothman identified in mammals, revealing an ancient evolutionary origin of the transport system. Collectively, they mapped critical components of the cell´s transport machinery.
Timing is everything
Thomas Südhof was interested in how nerve cells communicate with one another in the brain. The signalling molecules, neurotransmitters, are released from vesicles that fuse with the outer membrane of nerve cells by using the machinery discovered by Rothman and Schekman. But these vesicles are only allowed to release their contents when the nerve cell signals to its neighbours. How is this release controlled in such a precise manner? Calcium ions were known to be involved in this process and in the 1990s, Südhof searched for calcium sensitive proteins in nerve cells. He identified molecular machinery that responds to an influx of calcium ions and directs neighbour proteins rapidly to bind vesicles to the outer membrane of the nerve cell. The zipper opens up and signal substances are released. Südhof´s discovery explained how temporal precision is achieved and how vesicles´ contents can be released on command.
Vesicle transport gives insight into disease processes
The three Nobel Laureates have discovered a fundamental process in cell physiology. These discoveries have had a major impact on our understanding of how cargo is delivered with timing and precision within and outside the cell. Vesicle transport and fusion operate, with the same general principles, in organisms as different as yeast and man. The system is critical for a variety of physiological processes in which vesicle fusion must be controlled, ranging from signalling in the brain to release of hormones and immune cytokines. Defective vesicle transport occurs in a variety of diseases including a number of neurological and immunological disorders, as well as in diabetes. Without this wonderfully precise organization, the cell would lapse into chaos.
James E. Rothman was born 1950 in Haverhill, Massachusetts, USA. He received his PhD from Harvard Medical School in 1976, was a postdoctoral fellow at Massachusetts Institute of Technology, and moved in 1978 to Stanford University in California, where he started his research on the vesicles of the cell. Rothman has also worked at Princeton University, Memorial Sloan-Kettering Cancer Institute and Columbia University. In 2008, he joined the faculty of Yale University in New Haven, Connecticut, USA, where he is currently Professor and Chairman in the Department of Cell Biology.
Randy W. Schekman was born 1948 in St Paul, Minnesota, USA, studied at the University of California in Los Angeles and at Stanford University, where he obtained his PhD in 1974 under the supervision of Arthur Kornberg (Nobel Prize 1959) and in the same department that Rothman joined a few years later. In 1976, Schekman joined the faculty of the University of California at Berkeley, where he is currently Professor in the Department of Molecular and Cell biology. Schekman is also an investigator of Howard Hughes Medical Institute.
Thomas C. Südhof was born in 1955 in Göttingen, Germany. He studied at the Georg-August-Universität in Göttingen, where he received an MD in 1982 and a Doctorate in neurochemistry the same year. In 1983, he moved to the University of Texas Southwestern Medical Center in Dallas, Texas, USA, as a postdoctoral fellow with Michael Brown and Joseph Goldstein (who shared the 1985 Nobel Prize in Physiology or Medicine). Südhof became an investigator of Howard Hughes Medical Institute in 1991 and was appointed Professor of Molecular and Cellular Physiology at Stanford University in 2008.
Key publications:
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;
362:318-324.
Hata Y, Slaughter CA, Südhof TC: Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. Nature 1993; 366:347-351.
The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of mankind.
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