Victor Ambros named co-recipient of 2014 Gruber Genetics Prize

PUBLIC RELEASE DATE:

17-Jun-2014

Contact: Jim Fessenden james.fessenden@umassmed.edu 508-856-2000 University of Massachusetts Medical School

WORCESTER, MA Victor R. Ambros, PhD, professor of molecular medicine at the University of Massachusetts Medical School, has been awarded the 2014 Gruber Genetics Prize, along with long time collaborator Gary Ruvkun, PhD, professor of genetics at Massachusetts General Hospital and Harvard Medical School, and David Baulcombe, PhD, professor of botany at the University of Cambridge. Dr. Ambros, the Silverman Chair in Natural Sciences and co-director of the RNA Therapeutics Institute, and his scientific colleagues, received the prize for their pioneering discoveries of the existence and function of microRNAs and small interfering RNAs, molecules that are now known to play a critical role in gene expression.

"The discoveries of these three pioneering scientists have opened major new areas in chemistry, biology, agriculture and medicine, and have revealed fundamental mechanisms that are shared among organisms as diverse as plants and animals, including humans," said H. Robert Horvitz, PhD, Gruber and Nobel Prize laureate, and David H. Koch Professor at the Massachusetts Institute of Technology (MIT).

Established in 2001, the Gruber Genetics Prize is awarded for fundamental insights in the field of genetics and may include original discoveries in genetic function, regulation, transmission and variation, as well as in genomic organization. The prize, which is awarded along with a gold medal and an unrestricted $500,000 cash award, will be presented to the recipients in San Diego on Oct. 19 at the annual meeting of the American Society of Human Genetics.

The unlikely discovery of microRNAs, also known as miRNA, and their function dates back to the 1980s when Ambros and Dr. Ruvkun were both postdoctoral fellows in the lab of Dr. Horvitz at MIT, studying how the lin-4 and lin-14 genes regulate developmental timing in the nematode C. elegans. Ambros and Ruvkun wanted to understand how mutations of the lin-4 kept the worm's larvae from developing into fully formed animals, while mutations in the lin-14 gene caused the larvae to mature prematurely.

In 1989 Ambros established that lin-4 acts as a repressor of lin-14 activity. How lin-4 achieved this repression, however, was not known. In 1991, it was Ruvkun who established that genetic anomalies in lin-14's sequencespecifically in an area of the gene called the 3' untranslated region (3' UTR)were associated with excess production of the lin-14 protein produced from the messenger RNA that lin-4 targets.

A year later, Ambros successfully isolated and cloned lin-4. To his surprise, Ambros found that the gene's product was not a standard regulatory protein as he had expected, but a tiny non-protein-coding strand of RNA about 22 nucleotides long that is conserved in other nematode species.

Working together, Ambros and Ruvkun compared the lin-4 and lin-14 sequences and discovered that the 22-nucleotide lin-4 RNA and the 3' UTR were partially complementary and that the short complementary regions were highly conserved in evolutionary comparisons to other nematode lin-4 and lin-14 genes. They hypothesized that lin-4 RNA regulated lin-14 by binding to its 3' UTR sequences. Ruvkun then showed that lin-4 controlled the translation of the lin-14 mRNA into protein and it was through this channel that lin-4 achieved repression of lin-14.

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Victor Ambros named co-recipient of 2014 Gruber Genetics Prize