Victor Ambros, an alumnus of MIT, and Gary Ruvkun, who completed his postdoctoral training at the institution, have been awarded the 2024 Nobel Prize in Physiology or Medicine, as announced by the Royal Swedish Academy of Sciences this morning in Stockholm.
Ambros currently serves as a professor at the University of Massachusetts Chan Medical School, while Ruvkun is a professor at both Harvard Medical School and Massachusetts General Hospital. They received the award for their landmark discovery of microRNA, a group of small RNA molecules vital for gene regulation.
The Nobel committee highlighted that their research unveiled a new principle of gene control, which is essential for multicellular organisms, including humans. It is now understood that the human genome contains over a thousand microRNAs, illustrating a new aspect of gene regulation. The committee noted that microRNAs are crucial for the development and functioning of organisms.
Ambros and Ruvkun conducted their postdoctoral work in the late 1980s under the mentorship of H. Robert Horvitz at MIT, a notable figure who was awarded the Nobel Prize in 2002. In Horvitz’s lab, they began exploring gene regulation in the roundworm C. elegans, examining mutant strains that displayed developmental timing defects.
In the early 1990s, while Ambros was on the faculty at Harvard University, he made a pivotal finding: the lin-4 gene produced a short RNA molecule that inhibited the expression of lin-14 rather than coding for a protein. Simultaneously, Ruvkun continued his research on these genes at Massachusetts General Hospital and Harvard, uncovering that lin-4 did not inhibit lin-14 by blocking its transcription into messenger RNA but rather by preventing the production of its protein.
The researchers discovered that the lin-4 sequence matched certain short sequences in lin-14, leading to the conclusion that lin-4 binds to the messenger RNA of lin-14, blocking its translation into protein. This revealed a novel gene regulation mechanism that was previously unknown, with their findings published in two articles in the journal Cell in 1993.
In a conversation with the Journal of Cell Biology, Ambros acknowledged the important contributions of his collaborators, including his wife, Rosalind “Candy” Lee, and postdoctoral researcher Rhonda Feinbaum, who helped clone and characterize the lin-4 microRNA and co-authored one of the pivotal papers.
Ruvkun made another significant discovery in 2000 with the identification of the let-7 microRNA molecule, which is widespread in the animal kingdom. Since then, scientists have identified over 1,000 microRNA genes in humans.
The Nobel citation emphasized that Ambros and Ruvkun’s unexpected discovery in C. elegans opened up a new understanding of gene regulation, critical for all complex life forms.
Ambros hails from New Hampshire and was raised in Vermont; he earned his PhD at MIT under David Baltimore, a Nobel laureate in 1973. He previously taught at Dartmouth College before moving to the University of Massachusetts Chan Medical School in 2008. Ruvkun graduated from the University of California, Berkeley, and obtained his PhD from Harvard University before working in Horvitz’s lab at MIT.