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, currently a professor at the University of Massachusetts Chan Medical School, and Ruvkun, a professor at Harvard Medical School and Massachusetts General Hospital, received the prestigious honor for their pioneering discovery of microRNA, which are small RNA molecules vital for gene regulation.
The Nobel committee acknowledged their work, stating, “Their groundbreaking discovery revealed a completely new principle of gene regulation that turned out to be essential for multicellular organisms, including humans. It is now known that the human genome includes over one thousand microRNAs. Their surprising discovery opened an entirely new aspect of gene regulation. MicroRNAs are proving to be fundamentally important for how organisms develop and function.”
In the late 1980s, Ambros and Ruvkun were both researchers in H. Robert Horvitz’s laboratory at MIT. There, they studied gene regulation in the roundworm C. elegans, which became the foundation for their later Nobel-winning discoveries. They examined two mutant variants of the worm known as lin-4 and lin-14, which exhibited timing defects in activating genetic programs related to development.
During the early 1990s, while Ambros was at Harvard University, he made a groundbreaking finding: the lin-4 gene, instead of producing a protein, generated a very short RNA molecule that inhibited lin-14 expression. Simultaneously, Ruvkun investigated these genes at Massachusetts General Hospital and Harvard, discovering that lin-4 did not block the transcription of lin-14 messenger RNA, but rather suppressed its protein production later in the process.
As they compared their results, they realized that lin-4’s sequence was complementary to parts of lin-14. Their research demonstrated that lin-4 binds to lin-14 messenger RNA, preventing its translation into protein—a novel gene regulation mechanism. Their findings were published in two articles in the journal Cell in 1993.
In a later interview, Ambros acknowledged the contributions of his collaborators, including his wife, Rosalind “Candy” Lee, and postdoctoral researcher Rhonda Feinbaum, who helped characterize the lin-4 microRNA and co-authored one of the pivotal papers.
Later, in 2000, Ruvkun discovered another microRNA called let-7, found across the animal kingdom. Since then, over 1,000 microRNA genes have been identified in humans.
The Nobel citation praised Ambros and Ruvkun’s unexpected findings in C. elegans, which revealed a new dimension of gene regulation essential for complex life forms.
Ambros was born in New Hampshire and raised in Vermont and earned his PhD at MIT under David Baltimore, a Nobel laureate in 1973. He served on the faculty at Dartmouth College before joining the University of Massachusetts Chan Medical School in 2008. Ruvkun completed his undergraduate studies at the University of California, Berkeley, and earned his PhD from Harvard University before joining Horvitz’s lab at MIT.