Victor Ambros, an MIT alumnus, and Gary Ruvkun, who completed his postdoctoral training at MIT, will jointly receive the 2024 Nobel Prize in Physiology or Medicine, as announced by the Royal Swedish Academy of Sciences in Stockholm.
Ambros, a professor at the University of Massachusetts Chan Medical School, and Ruvkun, a professor at Harvard Medical School and Massachusetts General Hospital, have been recognized for their groundbreaking discovery of microRNA, a class of tiny RNA molecules crucial for gene regulation.
The Nobel committee highlighted 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 codes for over one thousand microRNAs. Their surprising discovery revealed an entirely new dimension to gene regulation, which is proving to be fundamentally important for how organisms develop and function.”
During the late 1980s, both Ambros and Ruvkun served as postdoctoral researchers in H. Robert Horvitz’s lab at MIT, where they began their investigation into gene control in the roundworm C. elegans, ultimately leading to their Nobel-worthy findings. Their research focused on two mutant strains of the worm, known as lin-4 and lin-14, which exhibited developmental timing issues due to genetic program activation defects.
In the early 1990s, while Ambros was at Harvard, he made a pivotal discovery that the lin-4 gene produced a very short RNA molecule rather than a protein and that this RNA inhibited lin-14 expression. Meanwhile, Ruvkun, working at Massachusetts General Hospital and Harvard, identified that lin-4 did not stop lin-14 transcription but rather inhibited its protein production at a later stage.
The two researchers collaborated and found that the lin-4 sequence matched short segments of lin-14, demonstrating that lin-4 binds to lin-14’s messenger RNA, preventing its translation into protein. This novel gene regulation mechanism was documented in two publications in the journal Cell in 1993.
In a related interview, Ambros acknowledged the contributions of his collaborators, including his wife, Rosalind “Candy” Lee, and postdoc Rhonda Feinbaum, who played roles in cloning and characterizing lin-4 microRNA.
Ruvkun went on to discover another microRNA molecule, let-7, which is pervasive in the animal kingdom, leading to the identification of over 1,000 microRNA genes in humans.
The Nobel citation celebrated Ambros and Ruvkun’s unexpected findings in C. elegans, emphasizing their contribution to understanding gene regulation in complex life forms.
Ambros hails from New Hampshire and grew up in Vermont. He earned his PhD from MIT under the guidance of Nobel laureate David Baltimore and spent many years at Dartmouth College before joining the University of Massachusetts Chan Medical School in 2008. Ruvkun graduated from the University of California at Berkeley and completed his PhD at Harvard, also working in Horvitz’s lab at MIT.