Venki Ramakrishnan

Before DNA was used to encode genetic information, life probably began as an RNA cell. world because RNA can both carry out catalysis or chemical reactions, but it can also store genetic information. And the earliest ribosomes were probably made just of RNA and were somehow used to make small random proteins. And eventually a coding mechanism evolved so that you started making coding proteins.

Before DNA was used to encode genetic information, life probably began as an RNA cell. world because RNA can both carry out catalysis or chemical reactions, but it can also store genetic information. And the earliest ribosomes were probably made just of RNA and were somehow used to make small random proteins. And eventually a coding mechanism evolved so that you started making coding proteins.

So that was the beginning of genetics, of gene-encoded protein synthesis. And it's an enormous machine. It was discovered in the 50s, but a human ribosome has about half a million atoms. And so even though it was discovered in the 50s and then people started to figure out what it was made off and what it did, the exact mechanism, how it actually worked remained a mystery for a long time.

So that was the beginning of genetics, of gene-encoded protein synthesis. And it's an enormous machine. It was discovered in the 50s, but a human ribosome has about half a million atoms. And so even though it was discovered in the 50s and then people started to figure out what it was made off and what it did, the exact mechanism, how it actually worked remained a mystery for a long time.

And that's because when you have a big complicated machine, if you don't know what it looks like, it's very hard to make detailed hypotheses about how it works. It's amazing that biochemists made as much progress as they did without ever having seen what a ribosome looked like.

And that's because when you have a big complicated machine, if you don't know what it looks like, it's very hard to make detailed hypotheses about how it works. It's amazing that biochemists made as much progress as they did without ever having seen what a ribosome looked like.

You know, that just shows how clever many biochemists are in doing the kinds of experiments where they could make inferences. But ultimately, solving the structure was a game changer. And it allowed people to do much more detailed mechanistic experiments to understand how it all worked. And now, you know, it's led the way to understanding how the ribosome is regulated, because that's

You know, that just shows how clever many biochemists are in doing the kinds of experiments where they could make inferences. But ultimately, solving the structure was a game changer. And it allowed people to do much more detailed mechanistic experiments to understand how it all worked. And now, you know, it's led the way to understanding how the ribosome is regulated, because that's

you know, you mentioned my book on aging, the connection between ribosomes and aging is that the regulation of ribosomes start to unravel as we get older. And so a lot of current works about ribosome regulation and regulation of protein synthesis.

you know, you mentioned my book on aging, the connection between ribosomes and aging is that the regulation of ribosomes start to unravel as we get older. And so a lot of current works about ribosome regulation and regulation of protein synthesis.

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.