Gruber Foundation Announces 2014 Gruber Genetics Prize Recipients

Gruber Foundation Announces 2014 Gruber Genetics Prize Recipients

The Gruber Foundation, a Type 1 supporting organization operated by Yale University, has announced the recipients of the 2014 Gruber Genetics Prize.

The prize, which recognizes groundbreaking contributions in genetics research, including genetic function, regulation, transmission, and variation, was awarded to Victor Ambros, professor of molecular medicine at the University of Massachusetts Medical School; David Baulcombe, professor of botany at the University of Cambridge; and Gary Ruvkun, professor of genetics at Massachusetts General Hospital and Harvard Medical School. The three scientists, who will share the $500,000 award, were recognized for their pioneering discoveries related to the existence and function of microRNAs and small interfering RNAs, molecules that are now known to play a critical role in gene expression.

In the 1980s, Ambros and Ruvkun were postdoctoral fellows in the lab of future Gruber and Nobel laureate H. Robert Horvitz, Ph.D., at the Massachusetts Institutes of Technology, studying the lin-4 and lin-14 genes that regulate developmental timing in the nematode Caenorhabditis elegans. In 1989, Ambros, at Harvard, established that lin-4 acts as a repressor of lin-14 activity, although the molecular mechanism for that repression awaited further investigation. In 1991, Ruvkun and his colleagues at Harvard lab established that genetic anomalies in lin-14's sequence were associated with excess production of the lin-14 protein produced from the messenger RNA that lin-4 targets. A year later, Ambros and his colleagues successfully isolated and cloned lin-4. Around the same time, Ruvkun demonstrated that particular elements of the lin-14 3' UTR are conserved in other nematodes, suggesting evolutionary selection on their function. 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 regions of complementarity 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 the repression mediated by lin-4 was via control of the translation of the lin-14 mRNA into protein.

The two scientists published back-to-back studies in Cell in 1993 that described their findings, but the idea that small RNAs might play a role in gene expression beyond C. elegans was not immediately clear. In 1999, David Baulcombe reported on his own groundbreaking discovery that a similar class of RNAs is involved in a related silencing process affecting viruses, transposable elements and gene expression in plants. This was followed the next year by Ruvkun’s twin discoveries that he had found a second microRNA — let-7 — in C. elegans and that let-7 was evolutionarily conserved across the animal kingdom, including in humans. In the years since, the study of small RNA has exploded into a new field in which scientists have linked the gene-silencing abilities of these tiny molecules to a diverse range of important developmental and physiological process in both plants and animals.

"At one time, these small RNAs were considered just an unimportant scientific oddity," says Huda Zoghbi, chair of the selection advisory board to the prize. "But thanks to the exciting work of Victor Ambros, Gary Ruvkun, and David Baulcombe, we now know that they are anything but unimportant, both to human health and to the health of the planet."