The 2017 Nobel Prize in Chemistry has been awarded to Jacques Dubochet of the University of Lausanne, Joachim Frank of Columbia University, and Richard Henderson of the MRC Laboratory of Molecular Biology in Cambridge, England. They earned the prize the development of cryo-electron microscopy, which both simplifies and improves the imaging of biomolecules. This method has moved biochemistry into a new era.
Why do we need cryo-electron microscopy?
Microscopes allow scientists to look at structures that cannot be seen with the naked eye-but when these structures are very tiny, it is no longer possible to use rays of light to do the job because their wavelengths are not short enough. Instead, beams of electrons can be used-with a technique known as transmission electron microscopy (TEM)-or scientists can employ a method known as x-ray crystallography in which x-rays are scattered as they pass through samples, creating patterns that can be analysed to reveal the structure of molecules.
Earlier imaging techniques, such as X-ray crystallography, required samples to be studied in a rigid state, revealing little about the dynamics of proteins and enzymes-many of which could not be successfully crystallised in any case. Another microscopic technique, the electron microscope, was only suitable for imaging dead matter, because its powerful beam destroyed delicate biological structures. Cryo-electron microscopy changes two of this. Researchers can now freeze biomolecules mid-movement and visualise processes they have never previously seen, which is decisive for both the basic understanding of life’s chemistry and for the development of pharmaceuticals.
What is cryo-electron microscopy?
“Cryo”, short for cryogenic refers to very low temperatures. Though the actual temperature is not well defined, it is below minus 150℃. In the context of electron microscopy, it refers to the fact that the object to be imaged is frozen to such low temperatures to facilitate being studied under the beam of the electron microscope.
This method is so effective that even in recent times, it has been used to image the elusive Zika virus: When researchers began to suspect that the Zika virus was causing the epidemic of brain-damaged newborns in Brazil, they turned to cryo-EM to visualise the virus. Over a few months, three dimensional (3D) images of the virus at atomic resolution were generated and researchers could start searching for potential targets for pharmaceuticals.
What’s next?
The trio’s work, and subsequent efforts to perfect these approaches, has already led to astonishing developments. “The technique of cryo-TEM has really opened up the molecular world of the cell to direct observation,” said Andrea Sella, professor of inorganic chemistry at University College London. But the future is also exciting, with scientists using the technique to probe the structure of drug targets, as well as components within cells involved in sensing pain, temperature and pressure. Further improvements in resolution are also afoot.