Cryo-electron microscopy emerged as a way to determine protein structures without needing to grow crystals, which is especially hard for membrane proteins. The technique freezes single protein particles without disrupting their shape, then uses computational algorithms to combine many two-dimensional images into an atomic-resolution three-dimensional structure. Early results were low-resolution and nicknamed 'blobology,' but the method matured over roughly two decades starting in 1981 into a high-resolution structural biology tool, earning a share of the 2017 Nobel Prize in Chemistry.
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The technique was developed as an alternative to X-ray crystallography, which requires protein crystals that are difficult or impossible to grow for many membrane proteins.
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The 'blobology' nickname came from how crude and low-resolution the earliest reconstructed images looked before computational methods improved.
190 words · auto-generated from the episode video
1:09:18it blobology because what he was trying to do is use electron microscopes to discern the structure of proteins. Well, people already had um the crystallization technique where you shoot X-rays at protein crystals and you get the structure. Well, you can't make crystals out of everything, especially membrane proteins. Those are hard to make crystals out of. And Wim Frank thought, okay, maybe if I image a bunch of these single particles in my slide and I have a good way to prepare them using this like really cool technique to freeze them but not like mess with their structure. And then I apply computation which had just been coming around, right? Computers had just been coming around. If I have some algorithms that
1:09:59can like discern what I'm looking at, then perhaps I can reconstruct to atomic resolution what the proteins look like. It took him like 20 years, but it started in 1981. He started with a paper that like I think was super blobby. So, hence blobology, >> but it became a high resolution structural tool and in 2017 he earned the Nobel Prize in chemistry.