A cold, clear view of life wins chemistry Nobel
Major advances in the imaging of biomolecules—everything from the needles that bacteria use to attack cells to the structure of Zika virus—have garnered three scientists the 2017 Nobel Prize for Chemistry. The award goes to three pioneers of a technique called cryo-electron microscopy: Jacques Dubochet of the University of Lausanne in Switzerland, Joachim Frank of Columbia University in New York City, and Richard Henderson of the Medical Research Council’s Laboratory for Molecular Biology (LMB) in Cambridge, United Kingdom.
The winners helped dramatically improve the resolution of biological molecules, including in 3 dimensions. “They’ve opened up a completely new world to us, to see these molecules in the cell and how they interact,” Peter Brzezinski, a biochemist at Stockholm University, said at this morning’s announcement in the Swedish capital. Further advances have brought cryo-EM within reach of resolving single atoms, rivalling x-ray crystallography. “We are facing a revolution in biochemistry,” said Nobel Committee chair Sara Snogerup Linse, a scientist a the Center for Molecular Protein Science at Lund University in Sweden.
The electron microscope has been around for a while—there were prototypes as early as 1931—but it had serious limitations for biologists. Samples must be contained in a vacuum, which dries out biological molecules and warps molecular structures. Then the samples are pelted by a beam of radiation that can fry sensitive biomolecules. Beginning in the 1950s, X-ray crystallography allowed biologists to create static images of the structure of proteins—if they could manage to crystallize them. And in the 1980s, nuclear magnetic resonance was providing the structure of proteins, but mostly for small proteins in solution.
Thanks to the efforts of today’s laureates and others, cryo-EM now offers a way to easily visualize many kinds of molecules, including important targets for new drugs. “It’s a direct method, easy to understand, and much more general in its power,” Henderson told Nobel.se in an interview today. He was attending a scientific meeting about cryo-EM this morning when he got the call that he would share the prize with Frank and Debochet. “I think that’s quite delightful, really.”
Henderson took a major step forward out of frustration with x-ray crystallography: He couldn’t coax proteins embedded in a cell membrane to crystallize. So he placed a bacterial cell membrane containing a protein called bacteriorhodopsin into an electron microscope and covered it in glucose to keep it moist. He then lowered the amount of energy in the beam, creating a low-contrast picture. Because the molecules were embedded in the membrane in an orderly fashion, Henderson got a diffraction pattern that he could turn into a higher resolution image. By 1975, he had created a 3-dimensional picture of the protein. It was, at the time, the finest ever portrait made of a protein with an electron microscrope. “This breakthrough proved the technology’s potential,” the Royal Swedish Academy of Sciences says in a press release. It was a bit of a special case because of the ordered arrangement of the proteins in the cell membrane, but in principle this approach could be used for any molecule found in cells.