Nobel Committee Secretary-General Thomas Perlmann speaks to the media in front of a picture of this year's laureates Victor Ambros and Gary Ruvkum during the announcement of the winners of the 2024 Nobel Prize in Physiology or Medicine, in Stockholm, Sweden, on Oct. 7.Christine Olsson/Reuters
A pair of U.S. researchers who uncovered a key mechanism governing the expression of genes have been awarded the Nobel Prize in Physiology or Medicine.
Victor Ambros, 70, of the University of Massachusetts medical school, and Gary Ruvkun, 72, of Massachusetts General Hospital and Harvard University, were named co-recipients of the medicine prize on Monday.
The two researchers are known for their work in the 1990s that led to the discovery of microRNAs – tiny molecular components within cells that can act as doorstops, delaying or blocking how genetic information encoded in DNA is translated into the proteins necessary for a wide range of life functions.
The finding has implications for human health and for the development of future therapeutics. For example, the disruption of microRNAs and their interactions with other molecules is one way that cancer cells can stimulate tumour growth. Researchers are currently seeking ways to counter this effect in cancer patients.
More broadly, the discovery of microRNAs is a matter of fundamental biology because it helps to answer the question of how genes are switched on and off – or how their effects are adjusted precisely in response to developmental and environmental cues.
“Today, we understand that the majority of genes are regulated by microRNAs,” said Olle Kampe, vice-chair of the Nobel Assembly at Sweden’s Karolinska Institute, which bestows the medicine prize each year.
As joint winners, Dr. Ambros and Dr. Ruvkun will share equally in a prize sum of 11-million Swedish krona ($1.4-million).
Although both are based in Massachusetts and have a long association, the two scientists conducted their Nobel-winning work largely independently of each other. It was their decision to share data at a crucial point that enabled their groundbreaking discovery, Dr. Kampe said.
During Monday’s announcement, he described how both Dr. Ambros and Dr. Ruvkun conducted their investigations using C. elegans, a type of roundworm that reaches only about one millimetre in length.
The tiny organisms have long been favoured by genetics researchers because they consist of only about 1,000 cells yet they share many features with humans, including a digestive tract, muscles and a nervous system.
When the two men began their work, biologists knew that the functions of different genes are expressed when information is copied from DNA onto a carried molecule known as messenger RNA. The long-stranded messenger RNA then leaves the nucleus of the cell, where the DNA resides, and finds its way to the cell’s protein-making machinery. There the information it carries is used to synthesize whatever proteins the cell needs.
Through their investigations, Dr. Ambros and Dr. Ruvkun showed that some areas of the DNA molecule are not used for making proteins. Instead they create short snippets called microRNAs that help guide other molecules to bind with and impede the message RNA. In doing so, they can slow down the production of a particular protein that may, in turn, be involved in amplifying or inhibiting a biological function.
From a functional perspective “they are sort of like volume controls on gene expression,” said Julie Claycomb, a professor of molecular genetics at the University of Toronto who works on microRNAs. “They can really turn down the volume on gene expression or they can turn it off all the way.”
The discovery of microRNAs, she added, amounted to a paradigm shift that has since evolved and expanded into a far more complex view of how networks of RNA molecules work together to control gene expression.
Dr. Claycomb did post-doctoral work at the University of Massachusetts between 2004 and 2011 and interacted regularly with Dr. Ambros, who was based there, and with Dr. Ruvkun during joint meetings with scientists at Massachusetts General Hospital.
She said that both scientists are a regular fixture in a monthly online seminar she organizes for specialists in the microRNA field, where their interest and input is often a catalyst for younger researchers.
“They’re curiosity-driven. They’re all in. They contribute so much to the community without even realizing they’re doing it,” she said.
Dr. Ambros was in Ottawa last week to present at a meeting organized by the newly created research consortium RNA Canada ARN. The organization seeks to promote RNA-related research in Canada, including the development of a national strategy.
The meeting, attended by about 500 scientists, was dedicated to various aspects of RNA science including vaccines for COVID-19 and other infectious disease – the subject of last year’s Nobel Prize for Medicine or Physiology.
In contrast with the development of RNA vaccines, microRNAs have not yet advanced into widely used treatments. Some have been tested in early phase clinical trials and the field remains a promising frontier for future therapeutics, particularly for cancer.
In 2008, Dr. Ambros and Dr. Ruvkun both received the Canada Gairdner International Award for their discovery. According to the Gairdner Foundation, they are the 99th and 100th winners of the Canadian award who have since gone on to win a Nobel Prize.