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| Source:nobelprize.org |
Together with Victor Ambros, Gary Ruvkin this year received the biggest award in the field of Nobel physiology.
The scientist born in Berkeley, March 26, 1952 is an American molecular biologist, researcher at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston.
Ruvkun discovered the mechanism by which lin-4, the first microRNA (miRNA) discovered by Victor Ambros, regulates the translation of its messenger RNA target through imperfect base pairing at the target, and discovered a second miRNA, let-7, and that these miRNAs are conserved throughout animal phylogeny, including in humans. The discovery of these miRNAs revealed a new world of RNA regulation at an unprecedentedly small size scale, and the mechanisms of such regulation. Ruvkun also discovered many features of insulin-like signaling in the regulation of aging and metabolism.
We will explain Ruvkun's contribution to winning the Nobel
Prize, as we took references from the nobel.org website.
Research on a small worm leads to a big breakthrough
In the late 1980s, Victor Ambros and Gary Ruvkun were
postdoctoral fellows in the laboratory of Robert Horvitz who was awarded the
Nobel Prize in 2002, alongside Sydney Brenner and John Sulston . In Horvitz’s
laboratory, they studied a relatively unassuming 1 mm long roundworm, C.
elegans. Despite its small size, C. elegans possesses many specialized cell
types such as nerve and muscle cells also found in larger, more complex
animals, making it a useful model for investigating how tissues develop and
mature in multicellular organisms. Ambros and Ruvkun were interested in genes
that control the timing of activation of different genetic programs, ensuring
that various cell types develop at the right time.
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| Ruvkun cloned let-7, a second gene encoding a microRNA. The gene is conserved in evolution, and it is now known that microRNA regulation is universal among multicellular organisms. © The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén |
They studied two mutant strains of worms, lin-4 and lin-14, that displayed defects in the timing of activation of genetic programs during development. The laureates wanted to identify the mutated genes and understand their function. Ambros had previously shown that the lin-4 gene appeared to be a negative regulator of the lin-14 gene. However, how the lin-14 activity was blocked was unknown. Ambros and Ruvkun were intrigued by these mutants and their potential relationship and set out to resolve these mysteries.
Gene regulation by microRNA, first revealed by Ambros and
Ruvkun, has been at work for hundreds of millions of years. This mechanism has
enabled the evolution of increasingly complex organisms. We know from genetic
research that cells and tissues do not develop normally without microRNAs.
Abnormal regulation by microRNA can contribute to cancer, and mutations in
genes coding for microRNAs have been found in humans, causing conditions such
as congenital hearing loss, eye and skeletal disorders. Mutations in one of the
proteins required for microRNA production result in the DICER1 syndrome, a rare
but severe syndrome linked to cancer in various organs and tissues.
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| The seminal discovery of microRNAs was unexpected and revealed a new dimension of gene regulation. © The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén |
Ambros and Ruvkun’s seminal discovery in the small worm C. elegans was unexpected, and revealed a new dimension to gene regulation, essential for all complex life forms.
Ruvkun received a Bachelor of Arts with a major in
biophysics from the University of California, Berkeley in 1973. He received a
Doctor of Philosophy in biophysics from Harvard University in 1982.He conducted
his doctoral studies in the laboratory of Frederick M. Ausubel, where he
investigated bacterial nitrogen fixation genes. Ruvkun completed postdoctoral
research with Robert Horvitz at the Massachusetts Institute of Technology (MIT)
and Walter Gilbert of Harvard