The 2017 Nobel Prize in Chemistry
The 2017 Nobel Prize in Chemistry has been awarded to Jacques Dubochet, Joachim Frank and Richard Henderson.
“for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution.”
Announced by the Nobel Prize committee on the 4th of October 2017 from Stockholm, the prize once again features the contributions of a British scientist. The award is attributed to three international scientists who worked to solve the problem of biological imaging, below is a summary of their story.
The story of the 2017 Nobel Prize award originates in Cambridge with Richard Henderson seeking to identify the structures of biological molecules. The complex nature of imaging such large scale structures meant systems such as X-ray crystallography were employed supplemented by Nuclear Magnetic Spectroscopy. However, the imaging of DNA or larger proteins was limited by these methods; fundamentally the need for a crystal structure meant protein dynamics could not be studied.
Instead Richard Henderson used electron microscopy, where a beam of electrons is sent through a sample, which can visualise small samples and even individual atoms. But this method itself is not without problems. Intense beams of electrons incinerate biological material and the method requires a vacuum, which evaporates water drying any sample.
Richard applied EM to the protein Bacteriorhodopsin which was coated in a naturally occurring glucose membrane which protected the protein when under vacuum. Furthermore, using a weaker electron beam, the regular packing of the protein structure could be imaged, although in a reduced contrast picture. Fifteen years later in 1990, Richard had improved his model through travelling to EMs across the world, leading to an atomic resolution image of Bacteriorhodopsin.
Joachim Frank’s contribution was in the application of mathematical models which differentiated between different recurring patterns of randomly positioned proteins. The patterns were sorted and merged to generate a single image, moving from multiple fuzzy EM images to a single sharper resolved image.
But the problem of sample drying remained for samples that could not be protected by a glucose membrane. The solution proposed by Jacques Dubochet’s involved the superfast cooling of samples. Conventional cooling leads to the formation of ice crystals, an undesired side-effect that leads to diffraction of the electron beam. Instead utilising super-fast cooling resulted in the solidification of water to form a glass. The preparation of biological samples was then simple enough for imaging using the electron microscopy method, thus became known as cryo-EM.
With advancing technology resolutions of electron microscopy has improved, studying larger systems to a greater resolution. Nowadays images have moved from a “blobology” image to more refined atomic resolution. In 2016, cryo-EM was used to provide high resolution images of the Zika virus.
Super-fast cooling has also lead to studying of biological dynamics. Each cooled protein acts as a single frame in a film which, when combined, allow the visualisation of protein interactions.
Nobel Committee Chairman Prof. Sara Snogerup Linse said: “We can see the intricate details of our biochemistry in every corner of our cells. We can understand how they are built and how they act and work together in large communities, we are facing a revolution in biochemistry.”
Closer to our department, the technique of electron microscopy is used by academics and researchers in the departments of Molecular Biology and Biomedical Sciences.