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. The Royal Swedish Academy of Sciences made this announcement today in Stockholm.
Ambros, who serves as 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 pioneering research on microRNA—tiny RNA molecules that play an essential role in gene regulation.
The Nobel committee highlighted their discovery as revolutionary, stating that it uncovered a novel principle of gene regulation critical for multicellular organisms, including humans. Currently, it is understood that the human genome contains over a thousand microRNAs, fundamentally influencing development and function in organisms.
During the late 1980s, both scientists conducted postdoctoral research under H. Robert Horvitz at MIT, who later received the Nobel Prize in 2002. In Horvitz’s lab, they focused their studies on gene control in the roundworm C. elegans, laying the foundation for their future Nobel-winning findings. They examined two mutant types of the worm, lin-4 and lin-14, which exhibited timing defects in genetic program activation during development.
In the early 1990s, while Ambros was a faculty member at Harvard University, he made a groundbreaking discovery: the lin-4 gene produced a short RNA molecule instead of a protein, inhibiting the expression of lin-14. Meanwhile, Ruvkun was continuing research in his lab at Massachusetts General Hospital and Harvard. He found that lin-4 did not stop lin-14 transcription into messenger RNA but effectively silenced the gene’s expression later on by blocking the production of lin-14 protein.
Upon comparing their findings, the two realized that lin-4 had a complementary sequence to certain short sequences of lin-14. They demonstrated that lin-4 binds to the messenger RNA of lin-14, preventing its translation into protein—a novel gene regulation mechanism previously unobserved. Their articles detailing these results were published in the journal Cell in 1993.
Ambros, in an interview with the Journal of Cell Biology, acknowledged the vital contributions of his collaborators, including his wife, Rosalind “Candy” Lee, and postdoc Rhonda Feinbaum, who were instrumental in cloning and characterizing the lin-4 microRNA.
In 2000, Ruvkun identified another microRNA molecule, let-7, which appears throughout the animal kingdom. Since then, over 1,000 microRNA genes have been discovered in humans.
The Nobel citation praised Ambros and Ruvkun’s work with C. elegans, describing it as unexpected and revealing, marking a significant advancement in the understanding of gene regulation essential for complex life forms.
Born in New Hampshire and raised in Vermont, Ambros earned his PhD at MIT under the mentorship of David Baltimore, a Nobel laureate himself. He was a faculty member at Dartmouth College until joining the University of Massachusetts Chan Medical School in 2008. Ruvkun graduated from the University of California at Berkeley and obtained his PhD from Harvard University before working in Horvitz’s lab at MIT.