This year’s Nobel Prize in Chemistry has been awarded to the coolest way to capture images of life’s molecular machinery – Cryo-Electron Microscopy.
In biology, structure is function. If you want to know how a protein or a virus or an enzyme works, you need to know what it looks like at the atomic scale. For decades, if you wanted to do this you would first need to crystalize your biomolecule (a slow and arduous process), then blast it with X-rays and then judge the shape of your molecule based on how the X-rays bounced off of it – a process known as X-ray Crystallography.
The famous Photo 51 captured by Rosalind Franklin in 1952 was the X-ray diffraction pattern that finally led to James Watson and Francis Crick’s breakthrough discovery of the molecular structure of DNA and spawned the genomics revolution. It took decades to achieve the clarity in Photo 51, and many 20th century scientists (save Franklin) captured the Nobel Prize on the back of X-ray Crystallography. But when compared to the high-definition images produced through Cryo-Electron Microscopy, Photo 51 looks like shadows on a wall.
Cryo-EM changed everything when it made the impossible possible. Electron Microscopes, which use beams of electrons to visualize atoms of matter, were first built in the 1930s, but there was no way to use them to visualize living matter – the powerful electron beams or the vacuum they required would incinerate or obliterate any biomolecules before an image could be captured.
This did not deter Professors Jacques Dubochet of the University of Lausanne, Switzerland, Joachim Frank of Columbia University, New York, USA and Richard Henderson of the MRC Laboratory of Molecular Biology, Cambridge, UK who were awarded the 2017 Nobel Prize in Chemistry today.
Through independent advances made by each of their labs throughout the 1980s and 90s this trio of researchers learned how to freeze biomolecules (hence the “cryo”) mid-movement in vitrified water (that’s water that has been flash frozen into glass) and the mathematical formulas our computers would need to resolve the image of the molecule in 3D! And since the molecules get frozen mid-movement, we can repeat this process to capture a series of images that can be threaded together into a motion picture movie – with Cryo-EM the field of structural biology has gone from shadow puppets to IMAX 3D.
In 2015, when the outbreak of the Zika virus was gaining speed, researchers were able to rapidly image the virus’ atomic structure using Cryo-EM and start the search for potential targets for pharmaceuticals in months rather than years. Cryo-EM is a game-changer. In the words of the Nobel Prize Committee, now that every hidden corner of the cell can be explored – “the sky is the limit”.