Venki Ramakrishnan
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Podcast Appearances
Yeah, that's true. And I think the science of visualization in molecular biology has advanced tremendously. I mean, first it was X-ray crystallography. And now more recently, there's cryo-electron microscopy. And also now predictive algorithms for protein domains and proteins using AI, which is also having a big impact in structural biology.
Yeah, that's true. And I think the science of visualization in molecular biology has advanced tremendously. I mean, first it was X-ray crystallography. And now more recently, there's cryo-electron microscopy. And also now predictive algorithms for protein domains and proteins using AI, which is also having a big impact in structural biology.
Yeah, the ribosome, as I said, it's large in molecular terms, but of course, it's only a couple of hundred nanometers across. So you can't really see it with an ordinary microscope, but you can see them under an electron microscope. And the big progress in the visualization field
Yeah, the ribosome, as I said, it's large in molecular terms, but of course, it's only a couple of hundred nanometers across. So you can't really see it with an ordinary microscope, but you can see them under an electron microscope. And the big progress in the visualization field
is that electron microscopy is advanced as a result of better detectors, better algorithms, faster detectors so that they can freeze the movement of particles while they're collecting the image. And that means that you can get high resolution atomic level images without using crystallography. So you don't even need crystals, which is what you needed for x-rays. And that was a big bottleneck.
is that electron microscopy is advanced as a result of better detectors, better algorithms, faster detectors so that they can freeze the movement of particles while they're collecting the image. And that means that you can get high resolution atomic level images without using crystallography. So you don't even need crystals, which is what you needed for x-rays. And that was a big bottleneck.
And the other thing about electron microscopy is you need tiny amounts of sample, and they don't even have to be pure. You can sort the particles computationally. So that has been a big game changer. And it struck me, there was a paper in BioRxiv just a few months ago where they had looked at ribosomes inside a cell. So they hadn't even broken open the cell to purify it.
And the other thing about electron microscopy is you need tiny amounts of sample, and they don't even have to be pure. You can sort the particles computationally. So that has been a big game changer. And it struck me, there was a paper in BioRxiv just a few months ago where they had looked at ribosomes inside a cell. So they hadn't even broken open the cell to purify it.
They just looked at thousands of ribosomes inside cells classified them into groups, and got a whole bunch of structures, each of which represents a snapshot of a ribosome. So what took us years of work, I mean, these guys did, you know, within weeks.
They just looked at thousands of ribosomes inside cells classified them into groups, and got a whole bunch of structures, each of which represents a snapshot of a ribosome. So what took us years of work, I mean, these guys did, you know, within weeks.
But that's just how science is, right?
But that's just how science is, right?
We did the painful way of... producing crystals which would take eight weeks to grow and were tiny. Then you'd have to take them to a synchrotron, these powerful x-ray sources, and hit them with x-rays and then analyze the data. And then eventually, if everything went well, you would get an image. And the first images were quite fuzzy. They were what we call low resolution images.
We did the painful way of... producing crystals which would take eight weeks to grow and were tiny. Then you'd have to take them to a synchrotron, these powerful x-ray sources, and hit them with x-rays and then analyze the data. And then eventually, if everything went well, you would get an image. And the first images were quite fuzzy. They were what we call low resolution images.
You couldn't see atomic detail, but you could see broader features, like you could see a double helix for the RNA. RNA, of course, also forms double helices like DNA. And when we saw that first double helix in the image of the ribosome, that was a very exciting moment because we knew that it was real because it had the features that you would expect. So it was a very exciting time.
You couldn't see atomic detail, but you could see broader features, like you could see a double helix for the RNA. RNA, of course, also forms double helices like DNA. And when we saw that first double helix in the image of the ribosome, that was a very exciting moment because we knew that it was real because it had the features that you would expect. So it was a very exciting time.
You know, I think... You know, smaller pieces of RNA had been already crystallized and their structures determined. So we knew that that's what RNA double helices should look like. I mean, the thing about the ribosome is not the structure of the individual pieces, but rather how they were put together in this large complex and how they interacted, how the different pieces interacted.
You know, I think... You know, smaller pieces of RNA had been already crystallized and their structures determined. So we knew that that's what RNA double helices should look like. I mean, the thing about the ribosome is not the structure of the individual pieces, but rather how they were put together in this large complex and how they interacted, how the different pieces interacted.
That's still basically the story. Of course, there are some genes which are never made into proteins. They stay as RNAs. And there are other parts of DNA and RNA that are involved in control, you know, start here or do this in response to this stimulus. So there are lots of control signals, but the part that codes for the protein
That's still basically the story. Of course, there are some genes which are never made into proteins. They stay as RNAs. And there are other parts of DNA and RNA that are involved in control, you know, start here or do this in response to this stimulus. So there are lots of control signals, but the part that codes for the protein