October 7, 2024
4 min learn
Nobel Prize in Physiology or Medication Awarded for Discovery of MicroRNA Gene Regulation
The 2024 Nobel Prize in Physiology or Medication was given to Victor Ambros and Gary Ruvkun for the invention of an necessary gene-manipulating mechanism in cells
Each cell in our physique begins out with the identical set of genetic directions, or DNA. But solely a few of these genes are expressed in every cell, resulting in the manufacturing of proteins that carry out the cell’s distinctive features. The 2024 Nobel Prize in Physiology or Medication was awarded on Monday to U.S. scientists Victor Ambros and Gary Ruvkun for the invention of microRNA, a molecule that performs this necessary regulatory course of.
The invention opened up a brand new area in gene regulation, explaining how solely a few of the many genetic directions in DNA end in practical proteins in several cells. The analysis was initially performed within the tiny roundworm Caenorhabditis elegans, however the mechanism has since been discovered within the genes of people and most different animals.
Ambros carried out his a part of the work at Harvard College, and he’s presently a professor of pure sciences on the College of Massachusetts Chan Medical College. Ruvkun carried out his analysis concurrently at Massachusetts Common Hospital and Harvard Medical College, the place he’s now a professor of genetics.
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“The seminal discovery of microRNA has launched a brand new and sudden mechanism of gene regulation,” mentioned Olle Kämpe, vice chair of the Nobel Committee for Physiology or Medication 2024, whereas describing the analysis throughout a press convention in Stockholm on Monday.
In cells, genes are transcribed into messenger RNAs (mRNAs), that are then translated into proteins. Proteins carry out the various very important features inside any cell, whether or not that cell is in nerve tissue, muscle or the immune system—or anyplace else. Issues with gene perform can result in situations comparable to most cancers, diabetes and autoimmune illness.
As early because the Sixties scientists had found that proteins known as transcription components might bind to genes and management what elements of these genes obtained transcribed into mRNA. This mechanism was considered the first manner genes have been regulated. However gene regulation turned out to be extra difficult than that.
Within the Eighties Ambros and Ruvkun have been working collectively as postdoctoral fellows on the laboratory of biologist Robert Horvitz, who shared the 2002 Nobel Prize in Physiology or Medication for describing the genetic regulation of cell dying in C. elegans. Researchers working with these organisms had beforehand found two “mutant” genetic types of the roundworm that developed in another way. One of many genes behind these types, generally known as lin-4, resulted in a bigger worm, whereas the opposite, lin-14, led to a smaller one. Ambros confirmed that the lin-4 gene was negatively regulating the lin-14 gene, nevertheless it wasn’t clear the way it did so.
Later, at Harvard, Ambros labored to “clone” or make copies of the lin-4 gene—however this resulted in a really tiny RNA molecule that was too small to supply a protein. On the similar time, Ruvkun, then at Mass Common and Harvard, was learning lin-14. He discovered that lin-4 was not blocking the manufacturing of lin-14 on the mRNA stage however was fairly impeding its translation into protein at some later stage. Ruvkun and Ambros determined to check their findings and located that a part of the sequence of lin-4’s RNA matched that of lin-14’s mRNA’s finish area, which isn’t concerned in encoding a protein. They found that the binding of this lin-4 RNA to lin-14’s mRNA prevented the latter from producing a protein. This represented a newly discovered mechanism of gene regulation that was orchestrated by tiny molecules known as microRNA.
At first, the researchers thought this mechanism is perhaps distinctive to C. elegans. However in 2000 Ruvkun recognized a second microRNA known as let-7 that was current in people and all through the animal kingdom. Scientists now know that people have greater than 1,000 totally different microRNA genes and that almost all of genes are regulated by microRNA.
The disruption of those microRNA networks is believed to play a job in how cancers develop, pointing towards potential therapies.
The Nobel winners’ key analysis was revealed in three research, together with two papers revealed in 1993 in Cell and one revealed in 2000 in Nature.
“I used to be astonished and stunned, delighted” on the information of the win, Ambros mentioned at a press convention on the UMass Chan Medical College on Monday morning. The importance of the invention of microRNA is that it made scientists conscious of “the very advanced and nuanced layer of regulation whereby genes and our cells speak to one another,” he mentioned. He emphasised the significance of laboratory organisms like the standard C. elegans, which he says are “completely the drivers of recent data within the life sciences.”
Ambros additionally famous that he and his spouse Rosalind “Sweet” Lee, who collaborated with him and co-authored one of many key research, have been the youngsters of immigrants from Poland and China, respectively. “I’m standing right here … due to the legacy of the parents who got here earlier than us,” Ambros mentioned.
At a press convention at Mass Common on Monday, Ruvkun mentioned, “It’s been morning,” including that “the science turned out to be nice in many various dimensions.” He thanked the lab colleagues he had labored with earlier, whom he mentioned amounted to in all probability 100 folks over 40 years.
The groundwork for the invention of microRNA was laid greater than a decade earlier than, within the early Eighties, says Bruce Wightman, a professor and chair of biology at Muhlenberg School. Wightman was a graduate scholar at Ruvkun’s lab at Harvard and co-authored one of many research underlying that discovery. And when he and his colleagues described that examine’s findings in 1993, their significance wasn’t instantly obvious. “There have been some individuals who actually thought that that was actually attention-grabbing and have been actually enthusiastic about it,” he says. “However there have been lots of people who thought it was just a few bizarre worm factor and wasn’t going to result in something broader.” Later it turned clear that microRNAs have been conserved by evolution in many of the animal kingdom and that a few of these in people play a crucial function in most cancers and different illnesses.
Ambros and Ruvkun “have been taking a look at two worms that regarded a bit humorous and determined to grasp why, after which they found a completely new mechanism for gene regulation,” Kämpe mentioned on the press convention. “I feel that’s lovely.”