The Nobel Prize in Chemistry 2017 has been awarded to Jacques Dubochet, University of Lausanne, Switzerland, Joachim Frank, Columbia University, New York, USA, and Richard Henderson, MRC Laboratory of Molecular Biology, Cambridge, UK, “for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution”.
Cryo-electron microscopy (cryo-EM) freezes mid-movement of biomolecules and allows to visualize processes that have never previously seen. This is important for the basic understanding of life’s chemistry and the development of pharmaceuticals.
In 1970, Richard Henderson generated a three-dimensional image of a protein at atomic resolution with an electron microscope. This proved the potential of the technology. Between 1975 and 1986, Joachim Frank developed an image processing method in which the electron microscope’s fuzzy two-dimensional images are analyzed and merged to give a sharp three-dimensional structure. In the early 1980s, Jacques Dubochet vitrified water by cooling it so rapidly that it solidifies in its liquid form around a biological sample. The biomolecules keep their natural shape even in the electron microscope’s vacuum. In 2013, optimizations lead to the desired atomic resolution, turning the technology into a routine application.
Jacques Dubochet, born 1942 in Aigle, Switzerland, received his Ph.D. in 1973 from the University of Geneva and University of Basel, both Switzerland. In 1967, he worked at the École Polytechnique de l’ Université de Lausanne (EPUL), Switzerland. Since 1987, he is Professor at the University of Lausanne. Currently, he is Honorary Professor of Biophysics there.
Joachim Frank, born 1940 in Siegen, Germany, received his Ph.D. in 1970 from the Technical University of Munich, Germany. Currently, he is Professor of Biochemistry and Molecular Biophysics and of Biological Sciences, Columbia University, New York, USA.
Among many other honors, Joachim Frank was awarded the 2017 Wiley Prize in Biomedical Sciences.
Richard Henderson, born 1945 in Edinburgh, Scotland, received his Ph.D. in 1969 from Cambridge University, UK. Currently, he is Programme Leader, MRC Laboratory of Molecular Biology, Cambridge, UK.
Selected Papers
J. Frank, Averaging of low exposure electron micrographs of non-periodic objects, Ultramicroscopy 1975, 1, 159-162. https://doi.org/10.1016/S0304-3991(75)80020-9
P. N. T. Unwin, R. Henderson, Molecular structure determination by electron microscopy of unstained crystalline specimens, J. Mol. Biol. 1975, 94, 425-432. https://doi.org/10.1016/0022-2836(75)90212-0
R. Henderson, P. N. T. Unwin, Three-dimensional model of purple membrane obtained by electron microscopy, Nature 1975, 257, 28-32. https://doi.org/10.1038/257028a0
J. Dubochet, M. Adrian, J.-J. Chang, J.-C. Homo, J. Lepault, A. W. McDowall, P. Schultz, Cryo-electron microscopy of vitrified specimens, Q. Rev. Biophys. 1988, 21, 129-228. https:/doi.org/10.1017/S0033583500004297
M. Adrian, J. Dubochet, J. Lepault, A. W. McDowall, Cryo-electron microscopy of viruses, Nature 1984, 308, 32-36. https://doi.org/10.1038/308032a0
J. Lepault, F. P. Booy, J. Dubochet, Electron microscopy of frozen biological suspensions, J. Microsc. 1983, 129, 89-102. https://doi.org/10.1111/j.1365-2818.1983.tb04163.x
J. Dubochet, J. J. Chang, R. Freeman, J. Lepault, A. W. McDowall, Frozen aqueous suspensions, Ultramicroscopy 1982, 10, 55-61. https://doi.org/10.1016/0304-3991(82)90187-5
J. Dubochet, J. Lepault, R. Freeman, J. A. Berriman, J. C. Homo, Electron microscopy of frozen water and aqueous solutions, J. Microsc. 1982, 128, 219-237. https://doi.org/10.1111/j.1365-2818.1982.tb04625.x
J. Dubochet, M. Adrian, J. Lepault, A. W. McDowall, Emerging techniques: Cryo-electron microscopy of vitrified biological specimens, Trends Biochem. Sci. 1985, 10, 143-146. https://doi.org/10.1016/0968-0004(85)90150-1
R. Henderson, J. M. Baldwin, T. A. Ceska, F. Zemlin, E. Beckmann, K. H. Downing, Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy, J. Mol. Biol. 1990, 213, 899-929. https://doi.org/10.1016/S0022-2836(05)80271-2
R. Henderson, The potential and limitations of neutrons, electrons and X-rays for atomic resolution microscopy of unstained biological molecules, Q. Rev. Biophys. 1995, 28, 171-193. https://doi.org/10.1017/S003358350000305X
P. B. Rosenthal, R. Henderson, Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy, J. Mol. Biol. 2003, 333, 721-745. https://doi.org/10.1016/j.jmb.2003.07.013
W. O. Saxton, J. Frank, Motif detection in quantum noise-limited electron micrographs by cross-correlation, Ultramicroscopy 1977, 2, 219-227. https://doi.org/10.1016/S0304-3991(76)91385-1
J. Frank, L. Al-Ali, Signal-to-noise ratio of electron micrographs obtained by cross correlation, Nature 1975, 256, 376-379. https://doi.org/10.1038/256376a0
J. Frank, W. Goldfarb, D. Eisenberg, T. S. Baker, Reconstruction of glutamine synthetase using computer averaging, Ultramicroscopy 1978, 3, 283-290. https://doi.org/10.1016/S0304-3991(78)80038-2
M. van Heel, J. Frank, Use of multivariates statistics in analysing the images of biological macromolecules, Ultramicroscopy 1981, 6, 187-194. https://doi.org/10.1016/0304-3991(81)90059-0
J. Frank, M. van Heel, Correspondence analysis of aligned images of biological particles, J. Mol. Biol. 1982, 161, 134-137. https://doi.org/10.1016/0022-2836(82)90282-0
M. Radermacher, T. Wagenknecht, A. Verschoor, J. Frank, A new 3D reconstruction scheme applied to the 50s ribosomal subunit of E. coli, J. Microsc. 1986, 141, RP1-RP2. https://doi.org/10.1111/j.1365-2818.1986.tb02693.x
M. Radermacher, T. Wagenknecht, A. Verschoor, J. Frank, Three-dimensional reconstruction from a single-exposure, random conical tilt series applied to the 50S ribosomal subunit of Escherichia coli, J. Microsc. 1987, 146, 113-136. https://doi.org/10.1111/j.1365-2818.1987.tb01333.x
A. Dashti, P. Schwander, R. Langlois, R. Fung, W. Li, A. Hosseinizadeh, H. Y. Liao, J. Pallesen, G. Sharma, V. A. Stupina, A. E. Simon, J. D. Dinman, J. Frank, A. Ourmazd, Trajectories of the ribosome as a Brownian nanomachine, Proc. Natl. Acad. Sci. USA 2014, 111, 17492-17497. https://doi.org/10.1073/pnas.1419276111
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ChemViews Mag. 2015.
Collection of information on the Nobel Prize - Discover research in Nobel winning field of Cryo-electron microscopy in Microscopy Research & Technique – free to download until end of 2017.
