Qu Chen is a senior laboratory research scientist in the Structural Biology team. She supports the cryo-electron microscopy pipeline, running collaborative projects while helping other teams across the Crick to use cryo-EM.
“In the 1950s, X-ray crystallography was the main way to see the 3D structure of molecules. This involves crystallising a molecule and using X-rays to show the structure. It’s great for small macromolecules, but there are limitations with using it for bigger macromolecules. A similar technique, X-ray diffraction, was used in the1953 papers to uncover the structure of DNA.
“In the 80s, cryo-electron microscopy was developed. The concept is to freeze a sample into a thin layer of ice and capture it using electrons to form images. With cryo-EM, the physiological state of the molecules is maintained. It was first used for big molecules like viruses, but with the resolution revolution in the 2010s, cameras became so much more sensitive and computers more powerful, so we were able to see much smaller molecules.
“A good example is the ribosome, the site where proteins are made. Researchers had been trying to solve the crystal structure of the ribosome since the 1970s, but because it’s big and flexible, it’s hard to crystallise, so it wasn’t until the 2000s that the first structure was produced using x-ray crystallography. But using modern cryo-EM, it only takes a few days to get a similar quality structure, as cryo-EM is a more suitable approach for this type of molecule.”
“Today, cryo-EM and X-ray crystallography are complimentary techniques to understand the structure of molecules. And we’re starting to be able to do even more, like cryo-electron tomography, where you can directly study macromolecules inside cells."