Venki Ramakrishnan
speaker
313 appearances
2 recordings
2 series
first heard Sep 2024
last heard 25 Apr
Venki Ramakrishnan’s voice in public audio — every appearance, attributed to the second.
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Appearances
to during stitching together a growing protein chain, you're going to add amino acids to the growing protein chain because amino acids are the building blocks. So that part where it's joined or the part where the genetic code is recognized in the ribosome, those parts are highly conserved. They're even conserved across kingdoms.
So there are only very small differences in the so-called peptidyl transfer center, which is where the amino acid bond is formed, peptide bond is formed. There are very subtle differences between, say, bacteria and humans. But overall, the ribosomes of bacteria look very different. For example, the human ribosomes are...
almost twice as large, and they've expanded both their RNA and protein components considerably.
Environmental factors, viruses. So I think part of the reason that eukaryotic, that is a translation in higher organisms, with a nucleus is more complicated, is because there's more regulation in higher organisms. And Initially, biologists thought that almost all of the regulation of genes had to do with how much and when you made mRNA from a section of DNA.
And that once the mRNA was made, the ribosome inevitably had to just do its thing, almost like a slave. But that's not how it is. It turns out that control exists both... at the mRNA production level, but also at the protein production level. So what we call translational control. And this means that the cell has ways of deciding when to start making proteins.
or it has ways of detecting when protein synthesis has gone wrong, when ribosomes have stalled because they've run out of amino acids. And what do you do about stalled ribosomes? So there's a whole series of control mechanisms and regulatory mechanisms. And the interesting thing is viruses will often hijack the ribosome. So they will shut down what's called the initiation machinery.
This is what tells the ribosome where to start on the mRNA. It doesn't start right at the extreme end. It has to start somewhere and then go along until it finds the first ribosome. codon, the first amino acid signal to be made. And that process of initiation is very complex. And what viruses do is they shut down the host initiation. So none of the host genes can be made into protein.
And then they have alternative ways of recruiting ribosomes to their own mRNA. And so they effectively hijack all of the ribosomes to make their message. In fact, the first gene product of coronavirus is something called NSP1. What NSP1 does is shuts down initiation from host mRNAs and somehow still allows coronavirus to make its own genes, you know, proteins from its own genes.
So there's a lot of... controlled regulation that's going on. And so even though the structure of the ribosome, the first structures came out from bacteria in about 2000, and then gradually we learned more and more about structure, the field is still going forward in all these complicated directions.
I don't think so. But as I've mentioned that there is this subset of the ribosome community that believes in specialized ribosomes. And they do have, you know, some data to support their view. So I think that it's still a matter of debate in the community. And it could be that there are specialized ribosomes. I wouldn't be completely surprised.
Although if you had to ask my personal opinion, I think that We still need to have stronger evidence for that.
People have already done that. So the structures of the ribosome do describe it in atomic detail. So we know the X, Y, and Z coordinate of every atom in one state of the ribosome. But remember, the ribosome is a highly dynamic machine. It moves around. It undergoes all sorts of processes. conformational changes. And so it's very much like watching a complicated machine which moves around.
Take a car, for instance. You have pistons that move around or a rotor that moves around in an electric car and wheels move and steering wheels move. So it's not a static object. And the ribosome itself is not static. It has complicated movements of its various component parts.
And what people are trying to do now is to simulate, using molecular dynamics, how the ribosome might move over time and as things bound to it, for example, the mRNA bound to it and the small adapter RNA molecules called tRNA molecules that bring in the amino acids to add to the protein in the ribosome.
So all of those things can change the conformation, the shape of the ribosome, because it's a dynamic machine. And people are trying to simulate that in computers.
I have to say, you know, I was a grad student in physics and I was trying to do condensed matter theory. And it was just so hard to make progress and do something interesting. And I used to subscribe to Scientific American. And I don't know if you remember, but in those days... all the articles were written by the primary scientists themselves, of course, with editorial help.
It was really very much a first person account. It was really thrilling. But what impressed me was that every issue had big questions in biology that were being answered left and right. And I thought, well, you know, this is probably where I should be
So right after my PhD, I went to grad school again at UCSD to study biology because I felt I didn't know any biology, so I didn't want to do a postdoc right away. Right, right.
Yeah, and I have to say, I thought I was in the middle of a revolution, but that revolution seems to still be going. It's been going for a long time. I would say ever since the discovery of the gene in the late 19th century, there's just been this steady onslaught of advances in biology. I liken it to how physics progressed very steadily after Galileo and Newton. and just kept on going.
And then when it was stalled, then suddenly you had quantum mechanics and relativity, and then there was another big wave. So I think biology is sort of behind physics by maybe a couple of hundred years. So it's not as mature a field as physics. And that's probably why I think physics is also harder, because it's more mature and the questions are harder.
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