Victor Ambros, an alumnus of MIT, and Gary Ruvkun, who completed his postdoctoral training at MIT, have been awarded the 2024 Nobel Prize in Physiology or Medicine, as announced by the Royal Swedish Academy of Sciences in Stockholm.
Ambros, now a professor at the University of Massachusetts Chan Medical School, and Ruvkun, a professor at Harvard Medical School and Massachusetts General Hospital, were recognized for their groundbreaking discovery of microRNA. These tiny RNA molecules are pivotal in regulating genes.
The Nobel committee highlighted that their discovery introduced an entirely new principle of gene regulation that is vital for multicellular organisms, including humans. It is now understood that the human genome contains over a thousand microRNAs, indicating the profound importance of this revelation for organism development and functioning.
In the late 1980s, both scientists worked as postdoctoral researchers in the lab of H. Robert Horvitz at MIT, who received a Nobel Prize in 2002. Their initial research focused on gene regulation in the roundworm C. elegans, specifically investigating mutations that exhibited developmental timing defects.
In the early 1990s, while Ambros was at Harvard, he discovered that the lin-4 gene produced a short RNA molecule that inhibited the expression of the lin-14 gene, rather than coding for a protein. Concurrently, Ruvkun was exploring these genes and demonstrated that lin-4 influenced lin-14’s expression later in the process, ultimately preventing the production of the associated protein.
By comparing their results, they identified that the lin-4 RNA sequence was complementary to parts of lin-14’s messenger RNA, blocking its translation into protein—a revolutionary mechanism of gene regulation. Their findings were published in two significant articles in the journal Cell in 1993.
Ambros acknowledged the vital contributions of his collaborators, including his wife, Rosalind “Candy” Lee, and postdoctoral researcher Rhonda Feinbaum, who played crucial roles in cloning and characterizing the lin-4 microRNA.
In 2000, Ruvkun uncovered another microRNA, let-7, which is prevalent across the animal kingdom. To date, more than 1,000 microRNA genes have been documented in humans.
The Nobel citation emphasized that the unexpected discovery made by Ambros and Ruvkun in C. elegans unveiled a new dimension to gene regulation essential to all complex life forms.
Ambros, originally from New Hampshire and raised in Vermont, earned his PhD at MIT under David Baltimore, who won a Nobel Prize in 1973. He was a faculty member at Dartmouth College before moving to the University of Massachusetts Chan Medical School in 2008. Ruvkun, a graduate of the University of California at Berkeley, obtained his PhD from Harvard University before joining Horvitz’s lab at MIT.