David Agard, a UCSF structural biologist, explains cryo-electron microscopy, which won the Nobel Prize for revealing how proteins fold and interact inside cells. His lab studies molecular chaperones, proteins that help other proteins fold correctly. Cryo-EM lets researchers see these structures in atomic detail, speeding up drug design.
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Hello!
This week the Nobel Prize in Chemistry was given to 3 scientists for developing cryo-EM. Here today we have David Agard, an expert in cryo-EM and also a QBI investigator as well as a professor at UCSF. Thank you for joining me today.
Yes, it's my pleasure.
So tell me, what is cryo-EM and how does it impact the world?
So cryo-EM is short for cryo-electron microscopy, and it's a new technique that allows us to study the three-dimensional structure of the important molecules inside of cells. And from that, we can figure out how they work. And that this is technology that while in principle people thought it might be possible many years ago, only recently through a handful of of combined advances has gotten to the point where we can really do this on a regular level. And, you know, this has excited the entire field and that excitement has been, and impact has been recognized in this Nobel Prize this year.
Great. And tell me, how does this lead to treatment or cures?
Yeah. So by figuring out the structure of the important machinery inside of cells, we can much more efficiently design drugs that can target those particular molecules. And so the machinery actually has very defined 3-dimensional shapes, and this is proteins, for example, that can do everything from help you sense heat or cold, see, you know, see light through your eyes, power your muscles. All of that sort of functionality is done by protein machines. And the ability to manipulate that with things that you take can help cure a particular disease in one particular area.
Okay, cool. And tell us a little bit about your work. How do you use this in your lab?
Yes. So cryo-EM has become very important to our work. And we've been studying the machinery inside of cells that actually helps the other machineries function. And so they're called chaperones because they help the other machines get into their proper state but then don't bother them too much once they're there. And so this wouldn't have been possible by any other method to understand their structure and function without using cryo-EM.
Okay, great. And can we check one out?
Sure.
Absolutely. All right.
And we're very excited here at UCSF that there's been a whole new center being developed for this technology, and we'll see that.
Okay, great. Stay tuned.
We have two EM suites here at UCSF. One that we've used for many years that has five microscopes in it, and this is the new one that's just come online in the first last couple months that has two of our, you know, biggest and most powerful microscopes. Come on in. Microscopes, they're called, um, uh, Krios machines. Cryo for cold. And that within this, these huge boxes that are about 14 feet tall, is where the sample gets loaded. And, you know, the microscope then takes pictures of that. And those pictures are then all processed by computers in order to generate the 3-dimensional structures of the molecules.
