Gary Ruvkun Shares Nobel Prize in Medicine

Harvard Medical School genetics professor honored  

Harvard University Professor Gary Ruvkun is jointly awarded the Nobel Prize in Medicine or Physiology. Victoria Ruvkun (from left) with dog Barnaby, Gary Ruvkun, and Natasha Staller are pictured the morning of the announcement at their home in Newton.

Harvard University Professor Gary Ruvkun is jointly awarded the Nobel Prize in Medicine or Physiology. Victoria Ruvkun (from left) with dog Barnaby, Gary Ruvkun, and Natasha Staller are pictured the morning of the announcement at their home in Newton.  | PHOTOGRAPH BY Stephanie Mitchell/Harvard Staff Photographer

Harvard Medical School professor of genetics Gary Ruvkun, Ph.D. ’82, has been named co-winner of the 2024 Nobel Prize in Physiology or Medicine, with Victor Ambros of the University of Massachusetts Medical School, in Worcester. The scientists were honored for their work on microRNA, a “fundamental principle governing how gene activity is regulated,” further summarized this way in the Nobel announcement:

The information stored within our chromosomes can be likened to an instruction manual for all cells in our body. Every cell contains the same chromosomes, so every cell contains exactly the same set of genes and exactly the same set of instructions. Yet, different cell types, such as muscle and nerve cells, have very distinct characteristics. How do these differences arise? The answer lies in gene regulation, which allows each cell to select only the relevant instructions. This ensures that only the correct set of genes is active in each cell type.

Victor Ambros and Gary Ruvkun were interested in how different cell types develop. They discovered microRNA, a new class of tiny RNA molecules that play a crucial role in gene regulation. 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. MicroRNAs are proving to be fundamentally important for how organisms develop and function.

Ruvkun’s webpage, which describes its work as “genetic analysis, genome analysis, and functional genomics,” details three themes in his research:

Research in the Ruvkun lab has explored three major themes: microRNA genes and other small RNAs, control of longevity and immune surveillance [covered in depth in Harvard Magazine’s feature, “The Aging Enigma”], and detection of life on other planets. We discovered in collaboration with Victor Ambros in 1992 that the first microRNA, lin-4, regulates the translation of a target gene, lin-14, to which it base pairs with the loops and bulges that are common in folded RNAs. The Ruvkun lab identified the second microRNA in 2000, let-7, which also regulates translation of its target gene via imperfect base pairing, and showed that the sequence and regulation of the let-7 microRNA is conserved across animal phylogeny including humans. Thousands of miRNAs across eukaryotic phylogeny were subsequently discovered by dozens of laboratories. The miRNA field has grown from the two back-to-back papers by Ambros and Ruvkun in 1993 to more than 100,000 references in 2021.

The discoveries’ scientific and clinical significance are further described thus:

miRNAs are now used in the clinic to type tumors. miRNAs are now implicated in heart disease, in viral pathogenesis, in regulation of neural function and disease, in the transition from totipotent stem cells to differentiated cells. In plants, miRNAs mediate a variety of developmental and physiological transitions and turn out to have been key players in the domestication of corn. Human therapies based on microRNA regulation are already in clinical trials for heart disease. We also discovered many of the genes that collaborate with microRNAs and siRNAs and other small RNAs. In addition to revealing fundamental regulatory axes in biology, some of these components may be developed as drug targets to enhance RNAi in animals and plants.

Ambros, who earned his undergraduate and doctoral degrees at MIT, was a Harvard faculty member from 1984 to 1992.

Read more articles by John S. Rosenberg

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