2017 Nobel Prize in Chemistry: Cryo-Electron Microscopy

The 2017 Nobel Prize in Chemistry was awarded earlier today to Jacques Dubochet, Joachim Frank, and Richard Henderson for their contribution to the development of cryo-electron microscopy (cryo-EM).

Left to right, Jacques Dubochet, Joachim Frank, and Richard Henderson. Credit: Nobel Media.

Left to right, Jacques Dubochet, Joachim Frank, and Richard Henderson. Credit: Nobel Media.

Chemistry is a crucial intermediary science, illuminating how the physics of atoms and molecules comes together to form complicated things like the biology of your brain. One of the main ongoing goals of chemistry is to create analytical techniques to identify and model molecules and how they interact.

The defining x-ray diffraction image which helped determine the structure of DNA. Credit: Wikipedia.

The defining x-ray diffraction image which helped determine the structure of DNA. Credit: Wikipedia.

Determining the shape of different molecules is crucial to understanding their properties and how they interact with other molecules. To figure out these structures, scientists have been developing imaging techniques for centuries. Microscopes revealed the structure of the microscopic, single-celled world in the late 17th century. By the middle of the 20th century, x-ray crystallography showed us the structure of DNA.

Looking at the diffraction patterns caused by purified and crystallized molecules has been and continues to be a revolutionary way to structures too tiny to be viewed with a conventional microscope.

Cryo-EM is the latest advancement in this long and storied tradition. Cryo-EM basically flash-freezes a sample of molecules and allows them to retain their shape when they are imaged in the vacuum of super high-resolution microscope that uses a beam of electrons. Since exploding onto the biochemistry scene in 2012-2013, cryo-EM has provided a huge leap in resolution for imaging molecular structures.

Comparison of resolution before and after introduction of cryo-EM. Credit: Royal Swedish Academy of Sciences.

Comparison of resolution before and after introduction of cryo-EM. Credit: Royal Swedish Academy of Sciences.

The three awardees of the Nobel Prize for cryo-EM each in their own way helped develop the technique.

Frank developed the method that combines multiple fuzzy two dimensional shadows from an electron microscope diffraction pattern into a single three dimensional structure.

Henderson was the first to actually figure out the three dimensional structure of a protein using an electron microscope.

Dubochet created the “cryo” part of cryo-EM, using a flash-freezing method that still keeps a bit of water on the sample molecules, which helps the molecules keep their shape.

Frank’s contribution of determining 3D structure from 2D shadows. Credit: Royal Swedish Academy of Sciences.

Frank’s contribution of determining 3D structure from 2D shadows. Credit: Royal Swedish Academy of Sciences.

Dubochet’s contribution of flash-freezing procedure. Credit: Royal Swedish Academy of Sciences.

Dubochet’s contribution of flash-freezing procedure. Credit: Royal Swedish Academy of Sciences.

The fact that cryo-EM can flash-freeze samples like this is a huge plus for chemists looking to characterize molecules in as close to their native forms as possible. Cryo-EM can even capture molecules mid-interaction, creating three dimensional frames of a movie playing out on a miniscule scale.

The development of cryo-EM is a recent boon to the field of chemistry, and scientists are only starting to reap the benefits. We wait with great anticipation all the fascinating things that cryo-EM will help discover!


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Fedor Kossakovski is a production assistant for Miles O'Brien Productions.