The video discusses the prestigious Nobel Prize in Physiology or Medicine for 2024, awarded to Victor Ambrose and Gary Ravkin for their groundbreaking discovery of microRNA and its pivotal role in post-transcriptional gene regulation. The presentation, led by Thomas Perlman, Secretary General of the Nobel Assembly, highlights the scientific breakthroughs of Ambrose and Ravkin, detailing their research conducted at Harvard University and Massachusetts General Hospital, respectively.

The Nobel Committee's vice-chair, Ulla Schempez, delves into the significance of microRNA in gene regulation. She elaborates on how genetic information transcribed from DNA into mRNA is historically understood, and explains how microRNA presents a novel mechanism by regulating protein synthesis at the mRNA level. This discovery is said to play crucial roles in various physiological processes and has critical implications for understanding diseases such as cancer. Despite substantial breakthroughs, immediate clinical applications of microRNA remain limited.

Main takeaways from the video:

Please remember to turn on the CC button to view the subtitles.

Key Vocabularies and Common Phrases:

1. regulation [ˌrɛɡjuˈleɪʃən] - (n.) - The act of controlling or maintaining a specific system. - Synonyms: (control, management, supervision)

The Nobel assembly at Karolinska Institute has today decided to award the 2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambrose and Gary Ravkin for the discovery of microRNA and its role in post transcriptional gene regulation.

2. transcript [ˈtrænˌskrɪpt] - (n.) - A written or printed version of material originally presented in another medium. - Synonyms: (record, manuscript, script)

So do show Nobel Fischamlingen with Karolinski Institute Tori dog Beslov that at Nobel Prize Victor Ambrose OC Gary Ravgen for uptechten of Microaren post transcription OK Poengelska the Nobel assembly at Karolinski Institute has today decided to award the 2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambrose and Gary Ravkin for the discovery of microRNA and its role in post transcriptional gene regulation

3. transcriptional [trænˈskrɪpʃənəl] - (adj.) - Related to the process of transcribing genetic information from DNA to RNA. - Synonyms: (transcribing, copying, rendering)

...for the discovery of microRNA and its role in post transcriptional gene regulation.

4. proteins [ˈproʊtiˌɪnz] - (n.) - Molecules that perform a wide array of functions within organisms by acting as enzymes, structural elements, etc. - Synonyms: (polypeptides, molecules, enzymes)

proteins are the building blocks that are responsible for major functions in our body.

5. mutants [ˈmjuːtənts] - (n.) - Organisms or cells that have undergone a change in genetic material, resulting in differences from the normal or original form. - Synonyms: (variation, deviant, anomaly)

Researchers had previously found two interesting s elegant mutants with timing defects during development.

6. embryological [ˌɛmbriəˈlɒdʒɪkəl] - (adj.) - Pertaining to the development of embryos, the early stages of an organism’s formation. - Synonyms: (developmental, fetal, prenatal)

Micrornas are important for our understanding of embryological development, normal cell physiology and diseases such as cancer.

7. conserved [kənˈsɜːrvd] - (adj.) - Maintained unchanged over a period despite pressures of evolutionary change. - Synonyms: (preserved, protected, sustained)

Unlike glean four, lead seven was found to be highly conserved and is present in human and most of the animal kingdom.

8. metastasize [məˈtæstəˌsaɪz] - (v.) - The process by which cancer spreads from the primary site to a different or secondary site within the host's body. - Synonyms: (spread, grow, mushroom)

...that tumors, if not most tumors, the micro rna networks are perturbed.

9. perturb [pərˈtɜːrb] - (v.) - To disturb or disquiet greatly in the mind; to agitate. - Synonyms: (disturb, unsettle, confuse)

...tumors, if not most tumors, the micro rna networks are perturbed.

10. silence [ˈsaɪləns] - (v.) - To make someone or something be quiet, not to express or emit sound. - Synonyms: (quiet, hush, shush)

...is rna binding, that binds up, and then you can have a specific mechanism to silence that rna binding protein.

Announcement of the 2024 Nobel Prize in Physiology or Medicine

So, ladies and gentlemen, good morning and very welcome to Nobel Forum for the announcement of this year's Nobel Prize in Physiology or Medicine. My name is Thomas Perlman and I'm the secretary general of the Nobel Assembly. I will first read the announcement in Swedish, followed by English, and then we will go on to present background to the prize and open up for questions.

The Nobel assembly at Karolinska Institute has today decided to award the 2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambrose and Gary Ravkin for the discovery of microRNA and its role in post transcriptional gene regulation. Here are the two laureates a few years ago Victor Ambrose was born in Hanover, New Hampshire, in the US in 1953. The work leading to today's award was performed at Harvard University and he's currently a Silverman professor of natural science at the University of Massachusetts Medical School. Gary Rufkin was born in Berkeley, California, in the US in 1952. The work leading to his Nobel Prize was performed at Massachusetts General Hospital and Harvard Medical School, where he's now a professor of genetics. I will now turn to the Nobel committee vice chair, Ulle Schempez, who will describe the discovery.

This year's Nobel laureates have discovered microorganin, a tiny molecule that has opened a new field in gene regulation. Genetic information is stored in DNA in the cell nucleus. This genetic information is copied into mRNA, and mRNA is then translated to protein. proteins are the building blocks that are responsible for major functions in our body. For example, neural function, muscle contraction, absorption of nutrients in the gut, and defending us from invading pathogens by immune cells. Different tissues express different proteins with different functions. Since the DNA in our cell nuclei contains exactly the same coding information in all cells, the question is, what determines that only the right genes are transcribed into mRNA and then translated into the correct tissue specific proteins at the right time? A first important step in gene regulation is governed by DNA binding proteins, so called transcription factors, ensuring that only the correct genes are transcribed into mRNA. As a result, the correct proteins are made in each specific cell type.

In fact, for many years it was believed that the main principles of gene regulation had been elucidated. The mechanism would, however, turn out to be more complex. For this year's Nobel Prize, an elegant little organism was the key. The tiny elegance has been used as a model for more than half a century. The worm contains only 1000 cells, but still forms many of the different tissues as humans do, including a nervous system, a gut, and muscles. Researchers had previously found two interesting s elegant mutants with timing defects during development. The lind four mutant with that red label, as shown on the slide, becomes larger because one developmental program, from egg to an adult worm is erroneously repeated. In contrast, the lin 14 mutant, as shown with the blue label, skips some stages during development and becomes smaller. The lin four and Lin 14 mutants have strikingly opposite appearances, and although the genes had not been cloned at the time, Victor Ambrose was able to show that lean four negatively regulated lean 14.

This year's Nobel laureates, Victor Ambrose and Gary Ravkin, were intrigued by this phenomenon and decided to attack the problem, identify the genese, and understand how these genes work. Victor Ambrose started an effort to clone lin four. Over several years, he made painstaking efforts to hum in on the exact position of the din. To the amazement of Victor Ambrose, when he finally cloned the lin for dinner, it only produced a tiny rna that could not be translated into a protein. Concurrently, Gary Ruffin succeeded in cloning the Lin 14 gene, which does translate into a protein, as shown in the box on the left. During early development of the worm seed elegance, the Lin 14 protein is made, but the production of lien 14 is suppressed by Lin four during the later stages of development. Gary Rufkin was intrigued when he found that the negative control of Lin 14 by Lin four seemed to involve the terminal segment of the lin 14 mRNA that was not translated, as depicted on the box on the right side. He observed that deletions of this region abolished the effect of Lin four, and therefore he postulated that the regulation might occur at the mRNA level.

The observations by Ambrose and Ravton were equally puzzling. How could these two, so very different molecules interact with each other? As Victor Ambrose and Gary Ravkin knew each other from their days as postdoctoral fellows, they decided to exchange information about the lean for and Lin 14 genes. On comparing their findings, it turned out that part of the sequence of the small lean four rna matched complementary sequences of lean 14 mRNA in the terminal region that does not code for a protein. They then understood that the binding of lean four to lean 14 mRNA prevented the production of the Lin 14 protein at the level of mRNA. At this point, they had discovered a novel and unexpected mechanism of gene regulation. Microrna. For a long time, however, microrna was believed to be an oddity peculiar to elegance this perception changed seven years later when Gary Rufkin in the year 2000 identified a second microrna produced by the lead seven gene in the world. Unlike glean four, lead seven was found to be highly conserved and is present in human and most of the animal kingdom.

This finding made the previously dormant microrna explode. As it turned out, many micrornas are highly conserved throughout evolution. Over several hundred million years. In more complex organisms, a larger number of micrornas have evolved, with humans having more than 1000. Distinction microrna genes today, we understand that the majority of all genes are regulated by micrornas. Every microrna regulates several genes, several mRNA's, and each mRNA is often regulated by many distinct micrornas, creating a robust system for gene regulation. The seminal discovery of microrna has introduced a new and unexpected mechanism of gene regulation. Micrornas are important for our understanding of embryological development, normal cell physiology and diseases such as cancer. As an example, tumors, often per term mitral rna networks in order to grow.

Victor Ambrose and Gary Rufkin have jointly been awarded this year's Nobel Prize in Physiology and medicine for their discovery of microrna and its role in post transcriptional regulation. I now hand back to Professor Thomas Palman, the secretary general of the Nobel assembly. Thank you very much, Ula. So with this, we would be happy to answer questions. And you already been introduced to Professor Schampert, but on my side I also have the chair of the Nobel committee, Professor Gunilla Colson hi Adestam, and member of the Nobel committee, Professor Richard San Barry.

We have a question up there first. Do I need a microphone? No, maybe not. Yes, yes, please. I have a question regarding your second last slide, if you could get back to that one. I wonder how it's possible for the microrna to get to the mRNA first, so to speak, so that it shuts down this mRNA and the protein is not made. I mean, if the mRNA is made first, then the protein would be made anyhow. And I also wonder what the different cell types. How, why is the microrna, a special microrna, active in one sort of a cell and not in another sort of a cell? Yes, these are quite advanced scientific questions and I'll turn to Professor Richard Chamberlain.

So, regarding the first question. So we skipped a lot of detail in this presentation, but the microrna strand is part of a protein complex that finds the mRNA in the cytoplasm. And there it can recruit other proteins that help shorten the poly tail, which leads to either translational inhibition or mRNA degradation. The second question about microrna genes, I mean, they are also transcribed, so they're copied from the DNA into their rna form, they're processed and that can be done. Cell type specifically. So a specific microrna will end up in a muscle cell, whereas other micro rna's end up in the, for example, nerve cells. And because of that, they can have cell type specific effects on the mRNA.

Hey, my name is Stefan Tromp from the german news agency dpa. Thomas, it's early morning in the US, so my question would be, have you already reached one of the laureates? And what did they say for being awarded? Yeah, nowadays it tends to be a little more difficult. People have mobile phones on silent. But I was able to wake up Gary Rumpkin, so I think he had a landline. I was able to reach him. His wife answered, and it took a long time before he came to the phone and sounded very tired. But he quite rapidly was quite excited and happy when he understood what it was all about. And he was so enthusiastic and his wife too. So he handed over the phone to his wife, who also wanted to talk to me for quite a while. And they were thrilled about the price and coming to Stockholm in December. I was not able to reach Victor Ambrose yet. I left a message on his mobile phone and hope he gives me a call soon.

Hello, my name is Bogun Radievsky, I'm from the polish television. A question I have is a little bit of comparison to the last year's Nobel prize. Because last year, with the Nobel Prize for the mRNA, the thing that we are most excited about, obviously, is what it can be used for, not only Covid vaccines, but also the prospect of cancer vaccines and solution to many diseases that we're facing today. So what about Microrna? How does it compare? And what could be the application of the discovery? Bye. This year's low yet. Thank you.

I think this is a very good question for Professor Colson Hildestam. Yes, thank you for that. So this year's prize is definitely a physiology prize. It helps us, our basic understanding of all of the things you heard about how cells differentiate and become specialized. Last year, of course, a much more applied discovery that was translated into vaccine development. So two quite different prices. But that said, having a basic understanding is of course the first step towards developing applications. So although there are no very clear applications available yet, micrornas, understanding them, knowing that they exist, understanding their kind of regulatory networks, is always the first step. So this could take a while. There are quite a lot of trials ongoing, and not only against cancer, but also in other diseases. The cardiovascular, kidney diseases. There are other trials ongoing, but nothing that is very sort of close to an actual sort of application. But we want to emphasize that the importance of understanding the basic functions, and that is always the first step towards using this knowledge.

I wonder if you are aware if the laureates have any patents on their discovery, and also if you could describe a little bit more about their collaboration. They were postdocs together. And how are their friends hanging out in the lab? Or what's their collaboration like? Ole champagne, maybe you want to. Well, they were postdoctoral fellows together, but then run separate labs and focusing partly on different aspects of the microarray. So the big findings were from 1993, when the first microrna was discovered by Viktor Ambrose, the Lin four mutant. And then seven years later, in 2000, Ravkin came with the second. So if there had been any patents that they no longer valid, right? Yes. Apir.

Hi, this is sunlight live weekly from China. A following up question about the clinical application, as Professor Hatterson mentioned that because microrna has been widely used as a research tool to modulate gene regulation, what is the main challenges to develop microrna as a drug or for its clinical applications? Maybe you can. Well, I think there are many problems. I mean, one thing is to deliver it to the right tissue. The second problem is, of course, that micrornas bind several targets. So you very easily get off target effects if you directly bind to one microrna. But there might be ways around that. Tumors quite often perturb the microrna networks, and they can do it by deleting the genes, or by mutating genese that process the microrna, or they can increase the production of rna binding protein that binds the microrna. And in that case, there are promising first tests to see if you can modulate the rnl binding protein. But to deliver micrornas to cells and think that you get one effect I think will be very difficult. Yes, thank you.

Hello. Paul Reese, Al Jazeera English if you had to explain in just a few words, as some of us may have to do later, what the difference is between mRNA and microrna, so that perhaps people don't get confused between this and last years. Yeah, I'll ask Ricard Saint Barry to explain the difference. Yes, so, I mean, mRNA is the very fundamental intermediate between our DNA and the proteins. And it's sort of this step that carries the information from the nucleus to the protein producing machinery. Micrornas, on the other hand, they are very short, and their primary role is to act as itself, as its rna form, where it instead interacts with mRNA's to tune or quite dramatically affect what amount of proteins can be made from it. Should we degrade the mRNA? So nothing to do with COVID vaccines this time? Sorry? So nothing to do with COVID vaccines this time? No, not really.

Let's see. Is there any other question? I know it's as usual that many are eager for the interview, since that after the press conference. But still, if there is any pressing question, there is still time, if anyone would be interested in something. If not, then thank you so much for coming here today and we'll see several of you at interviews. Thank you.

Professor Ulissempe, member of the Nobel committee. Can you summarize what this year's Nobel Prize was awarded for? What it was once awarded for? It was awarded for micrornal. And well, micrornal is a new layer in gene regulation, creating a network that makes gene regulation much more robust. My coordinate is a kind of a complex concept for most of us. Could you please explain it a bit more in detail?

So this was discovered the first microrna by Victor Ambrose in 1993. But it was thought to be an I oddity peculiar to a small worm. This is elegance. For more than seven years, until Gary Rutkin detected the second microrna lead seven. And then it sort of, the field exploded. And now more than tens of thousands of microrna have been identified in different organisms. So it's been evolutionary conserved over several hundred million years and present in almost all animals. So it must be important, right? And the importance is to create this very robust network. So each microrna, which is a tiny molecule, binds to several mRNA's. MRNA's is the intermediate between our genes and our proteins. So it takes the information from the gene and makes the protein. But then it's modulated by this microrna network. And this was a finding that was completely unexpected. No one thought, everyone thought the major problem in gene regulation had already been solved. But it's just the last 1020 years. We understand there's a different layer that is equally important.

How does the discovery affect our daily lives? Well, it affects our daily life in the that as researchers, we have a much better understanding how cells work. And we can see that in many tumors, if not most tumors, the micro rna networks are perturbed. So the tumor takes advantage of this and tries to take away the microrna genese or silence them. We don't have yet any way to treat these disorders where microarray networks are perturbed. But we hope that someday that will come it's the knowledge that is important.

So if I understand it correctly, there are no clear medical applications yet. In the future? There might be in the future, and there might be special cases. So some tumors delete the micrornas, others mutate them, but there are also other mechanisms that, like increasing a protein, that is rna binding, that binds up, and then you can have a specific mechanism to silence that rna binding protein.

So if we turn to this year's laureates, Victor Ambrose and Gary Rupkin, could you please tell us a little bit about them? Well, they are born in 1952 and 1953. They did their postdoctoral experience in the same lab with a former Nobel Prize, Robert Horwitz. But after that they went to Harvard University and Harvard Medical School, respectively, and set up their own labs and worked on different aspects of microrna regulation. So Victor Ambrose was the first one to clone a microrna, and Rutkin Hill cloned the second one, and he was the one to propose that the regulation was at the mRNA level. So they made different. But they haven't collaborated a lot after the postdoctoral work, as much as I know.

But they did actually share some data between them? Yes, they did. And that was the key to this Nobel Prize, that they met and shared information and could see that the lean four gene actually matched a complementary sequence of Lin 14. And then this concept of the regulation at the mRNA level, and not only at the gene level, was born. And I understand that Thomas Perelman was able to get in touch with at least one of them, Gary Rutkin. He answered very early in the morning, I think, 04:00 their time. His wife, in fact, according to Thomas, who answered, and, well, I guess his wife became happier than he. Looking forward to come to Stockholm.

And finally, could you please tell me 30 seconds, why are you excited by this year's prize? I think it's one of the big Nobel prizes because it's a completely new physiological mechanism that no one expected completely out of the blue. And it shows that curiosity research is very important. They were looking at two worms that looked a bit funny and decided to understand why. And then they discovered an entirely new mechanism for gene regulation. I think that's beautiful. Professor Ulischempe, thank you very much for guiding us through this year's. Thank you for having me. Thanks.

Nobel Prize, Genetics, Physiology, Science, Harvard, Innovation, Nobel Prize