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Nobel Prize in Chemistry Awarded for 3D Views of Biological Molecules Nobel Prize in Chemistry Awarded for 3D Views of Life’s Biological Machinery
(about 4 hours later)
Jacques Dubochet, Joachim Frank and Richard Henderson were awarded the Nobel Prize in Chemistry on Wednesday for developing a new way to construct precise three-dimensional images of biological molecules, potentially leading to, a revolution in how scientists study the inner workings of cells. Three European-born scientists were awarded the Nobel Prize in Chemistry on Wednesday for developing a new way to assemble precise three-dimensional images of biological molecules like proteins, DNA and RNA.
The Nobel committee said the technique, cryo-electron microscopy, could lead to “detailed images of life’s complex machineries in atomic resolution,” enabling biologists to study certain aspects of cells that were previously invisible. Their work has helped scientists decipher processes within cells that were previously invisible, and has led to better understanding of viruses like Zika. In the future, their techniques could offer road maps in the development of drugs to treat diseases.
“Soon there are no more secrets,” said Sara Snogerup Linse, a professor of physical chemistry at Lund University in Sweden who was the committee chairwoman. “Now we can see the intricate details of the biomolecules in every corner of our cells, in every drop of our body fluids.” The winners are Jacques Dubochet, a retired biophysicist at the University of Lausanne in Switzerland; Joachim Frank, a professor at Columbia University in New York; and Richard Henderson, a scientist at the British Medical Research Council’s Laboratory of Molecular Biology in Cambridge, England.
It has already helped scientists better understand diseases like Zika virus, and could lead to treatments in the future. The Nobel committee said the technique, cryo-electron microscopy, produces “detailed images of life’s complex machineries in atomic resolution.”
Cryo-electron microscopy makes it possible to record images of biomolecules after freezing them very quickly, allowing their natural shape is preserved, the Nobel committee said. “Soon there are no more secrets,” said Sara Snogerup Linse, a professor of physical chemistry at Lund University in Sweden who chaired the committee for the chemistry prize. “Now we can see the intricate details of the biomolecules in every corner of our cells, in every drop of our body fluids.”
Figuring out the shape of a protein is crucial to figuring out its function. The structure of a virus, for instance, gives essential clues to how it invades a cell. For decades, the main method for studying protein structure was stacking many copies of a protein into a crystal, bouncing X-rays off the crystal and then deducing the protein shape using the patterns of X-ray reflections. Dr. Henderson said during a news briefingin Cambridge that he was delighted to share the prize.
He was at a conference listening to a talk when he was called by the Swedish Academy of Science, which administers the prizes.
“I rejected the phone call,” he said. “Then it rang again.”
He also recognized others who had contributed to the technique’s development.
“I think the feeling is that the three of us who have been awarded the prize are sort of acting on behalf of the whole field,” Dr. Henderson said. “It’s kind of a worldwide effort that’s just now come to fruition.”
Dr. Frank received his phone call at 5:18 a.m. New York time. He said recently his dog has been barking earlier and earlier in the morning, waking up him and his wife. “This time it was not the dog,” he said.
Figuring out the shape of proteins and other biological molecules is crucial to understanding their functions. The structure of a virus, for instance, gives essential clues to how it invades a cell.
For decades, the main method for studying protein structure was stacking many copies of a protein into a crystal, bouncing X-rays off the crystal and then deducing the protein shape using the patterns of X-ray reflections.
But many proteins, especially those embedded in the outer membranes of cells, are too floppy or disordered to crystallize.But many proteins, especially those embedded in the outer membranes of cells, are too floppy or disordered to crystallize.
Dr. Henderson, of the MRC Laboratory of Molecular Biology in Cambridge, England, started his career as an X-ray crystallographer. Stymied by the limitations, he turned to a different instrument, the electron microscope. Dr. Henderson started his career as an X-ray crystallographer, but stymied by the limitations, he turned to a different instrument: the electron microscope.
Electron microscopes were invented in 1931. But they operate in a vacuum and bombard samples with electrons, so they are ill-suited for studying proteins and other biological molecules. They dried the samples and damaged them with radiation. Electron microscopes, invented in 1931, use a beam of electrons to produce images with a finer resolution than what is possible with a conventional microscope. But they operate in a vacuum where biological samples dry out. The bombardment of electrons also damaged the molecules.
For the particular protein that Dr. Henderson and his colleagues wanted to study, embedded in the membrane of a photosynthesizing organism, the vacuum was not an insurmountable problem. They left the protein embedded in the membrane and protected it with a glucose solution to prevent it from drying out. The particular protein that Dr. Henderson and his colleagues wanted to study was embedded in the cell membranes of a photosynthesizing organism, and they used a coating of glucose solution to prevent it from drying out.
They also turned down the intensity of the electron beam and took advantage of the regular arrangement of the proteins in the membrane. That allowed Dr. Henderson, in 1975, to reconstruct the shape of the protein from the scattering of the electrons, almost the same mathematical analysis he had used for X-ray crystallography.They also turned down the intensity of the electron beam and took advantage of the regular arrangement of the proteins in the membrane. That allowed Dr. Henderson, in 1975, to reconstruct the shape of the protein from the scattering of the electrons, almost the same mathematical analysis he had used for X-ray crystallography.
For most proteins, scientists could not rely on a protein being embedded in a regular pattern, all oriented in the same direction. Dr. Frank, of Columbia University, came up with the next advance honored by the Nobel committee. He recorded images of many copies of a protein at one-time, scattered in random orientations. A computer grouped together similar images — the proteins that were in similar orientations — and combined them to produce a sharper result. From the combined orientations, he was also able to put together the three-dimensional shape. For most proteins, scientists could not rely on a protein being embedded in a regular pattern, all oriented in the same direction.
Dr. Dubochet, of the University of Lausanne, Switzerland, further refined the technique — quick-freezing the molecules to protect them from the vacuum. But in ice, water molecules usually stack into a crystal shape, and the bouncing of electrons off the ice crystals in a frozen sample resulted in useless images. In the 1970s and 1980s, Dr. Frank came up with the next advance honored by the Nobel committee. He recorded images of thousands or millions of copies of a protein at one-time, scattered in random orientations.
To overcome this problem, Dr. Dubochet dipped the samples in liquid nitrogen-cooled ethane. At minus 321 degrees Fahrenheit (minus 196 Celsius), the water molecules froze so quickly that they had no time to line up in crystals, solidifying instead into a random structure, more like glass. That enabled the electron microscope technique to view the embedded proteins instead of the ice. “Then you have a chance of capturing all the projections that you need,” Dr. Frank said in an interview. “The only problem is to find out the orientation of the molecules. That’s the hard part.”
The technique is already driving some scientific advances. Last year, scientists were able to use cryo-electron microscopy to analyze the structure of the Zika virus, the mosquito-borne virus that causes birth defects. The same technique was used to figure out the structure of proteins involved with circadian rhythms, advances that were recognized with this year’s Nobel Prize in Medicine. A computer grouped together similar images — the proteins that were in similar orientations — figured out how they were arranged and combined them to produce a sharper result. The many orientations essentially offered views of the same molecule from different angles. He was also able to put together three-dimensional shapes.
Jacques Dubochet, 75, is a Swiss citizen. He retired from the University of Lausanne in Switzerland in 2007. His web page at the university humorously notes that in October 1941, he was “conceived by optimistic parents” and in 1946 he was “no longer scared of the dark, because the sun comes back.” He noted of his dyslexia: “This permitted being bad at everything … and to understand those with difficulties.” Dr. Dubochet, of the University of Lausanne, Switzerland, invented the “cryo” part of cryo-electron microscopy. “He’s the real father of the field,” Dr. Henderson said.
Joachim Frank, 77, was born in Germany and is now a citizen of the United States. He is a professor of biochemistry and molecular biophysics Columbia University in New York. He is also an investigator for the Howard Hughes Medical Institute and a member of the National Academy of Sciences. In 2014, he received the Benjamin Franklin Medal in Life Science from the Franklin Institute in Philadelphia. Embedding the molecules in ice would also protect them from drying out. But in ice, water molecules usually stack into a crystal shape, and the bouncing of electrons off the ice crystals in a frozen sample yielded useless images.
Richard Henderson, 72, was born in Scotland and is a British citizen. He has worked at the British Medical Research Council’s Laboratory of Molecular Biology in Cambridge since 1973. He served as the laboratory’s director from 1996 to 2006. To overcome this problem, Dr. Dubochet dipped the samples in liquid nitrogen-cooled ethane. At minus 321 degrees Fahrenheit (minus 196 Celsius), an ultrathin layer of water molecules froze so quickly that they had no time to line up in crystals, and they solidified into a glass-like structure. That enabled the electron microscope technique to view the embedded molecules instead of the ice.
Advances in the detectors of electron microscopes now provide enough clarity to pinpoint each and every atom in the molecules. The blobby protein that Dr. Henderson originally imaged in 1975 can now be studied precisely.
The technique is already driving some scientific advances. Last year, scientists were able to use cryo-electron microscopy to analyze the structure of the Zika virus, the mosquito-borne virus that causes birth defects.
“We could never have done that with crystallography on its own,” said Michael Rossmann, a professor of biological sciences at Purdue University in Indiana who led the research that produced the Zika structure.
He said that he and his colleagues have identified sites on the virus where antibodies can attach and disable Zika. That could lead to the development of antiviral drugs.
The same technique was used to figure out the structure of proteins involved with circadian rhythms, advances that were recognized with this year’s Nobel Prize in Medicine.
Only a small number of institutions can perform cryo-electron microscopy. The microscope apparatus costs millions of dollars. Dr. Henderson likened the technique to DNA sequencing — once laborious and costly, now commonplace and affordable.
He imagined that the same will happen for biologists wanting to know the structure of a protein. “You send it off, teatime, and the next morning, you get the structure back by email,” he said.
Dr. Frank said he had yet to decide what to do with his one-third share of the $1.1 million prize money. “I haven’t discussed this with my wife,” he said. “One thing I told her is we don’t have to worry about dogsitting anymore.”
Dr. Dubochet, 75, is a Swiss citizen. He retired from the University of Lausanne in Switzerland in 2007. His web page at the university humorously notes that in October 1941, he was “conceived by optimistic parents” and in 1946 he was “no longer scared of the dark, because the sun comes back.” He noted of his dyslexia: “This permitted being bad at everything … and to understand those with difficulties.”
Dr. Frank, 77, was born in Germany and is now a citizen of the United States. He is a professor of biochemistry and molecular biophysics Columbia University in New York. He was also an investigator for the Howard Hughes Medical Institute and a member of the National Academy of Sciences. In 2014, he received the Benjamin Franklin Medal in Life Science from the Franklin Institute in Philadelphia.
Dr. Henderson, 72, was born in Scotland and is a British citizen. He has worked at the British Medical Research Council’s Laboratory of Molecular Biology in Cambridge since 1973. He served as the laboratory’s director from 1996 to 2006.
■ Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded the Nobel Prize in Physiology or Medicine on Monday for discoveries about the molecular mechanisms controlling the body’s circadian rhythm.■ Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded the Nobel Prize in Physiology or Medicine on Monday for discoveries about the molecular mechanisms controlling the body’s circadian rhythm.
■ Rainer Weiss, Kip Thorne and Barry Barish received the Nobel Prize in Physics on Tuesday for the discovery of ripples in space-time known as gravitational waves.■ Rainer Weiss, Kip Thorne and Barry Barish received the Nobel Prize in Physics on Tuesday for the discovery of ripples in space-time known as gravitational waves.
Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard L. Feringa were recognized for their development of nanomachines, made of moving molecules, which may eventually be used to create new materials, sensors and energy storage systems.Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard L. Feringa were recognized for their development of nanomachines, made of moving molecules, which may eventually be used to create new materials, sensors and energy storage systems.
Three more will be awarded in the days to come:Three more will be awarded in the days to come:
■ The Nobel Prize in Literature will be announced on Thursday in Sweden. Read about last year’s winner, Bob Dylan.■ The Nobel Prize in Literature will be announced on Thursday in Sweden. Read about last year’s winner, Bob Dylan.
■ The Nobel Peace Prize will be announced on Friday in Norway. Read about last year’s winner, President Juan Manuel Santos of Colombia.■ The Nobel Peace Prize will be announced on Friday in Norway. Read about last year’s winner, President Juan Manuel Santos of Colombia.
■ The Nobel Memorial Prize in Economic Science will be announced on Monday, Oct. 9, in Sweden. Read about last year’s winners, Oliver Hart and Bengt Holmstrom.■ The Nobel Memorial Prize in Economic Science will be announced on Monday, Oct. 9, in Sweden. Read about last year’s winners, Oliver Hart and Bengt Holmstrom.