Gary Ruvkun, HMS professor of genetics at Massachusetts General Hospital, has been named a corecipient of the 2008 Lasker Award for Basic Medical Research. Ruvkun, along with collaborators Victor Ambros and David Baulcombe, is recognized for his role in the discovery of microRNAs—tiny molecules of RNA that bind to regulatory segments of their target genes’ RNA and block gene expression.
The Lasker Awards recognize outstanding contributions in medical research. In addition to the award for basic medical research, prizes are awarded in the categories of clinical medical research and special achievement in medical science. Called “America’s Nobels,” the Lasker Awards are considered one of the greatest honors in medical research. Ruvkun and colleagues will share the $300,000 prize.
In the early 1980s, Ruvkun and Ambros were both fellows in the Massachusetts Institute of Technology laboratory of Robert Horvitz, investigating genes that control development in C. elegans. They worked together to isolate a gene called lin-14 that operates in concert with the gene lin-4 to regulate the worms’ transition through key developmental stages.
As the two researchers established their own laboratories—Ruvkun in the MGH Department of Molecular Biology and Ambros at Harvard—they continued collaborating to uncover how the two regulatory genes interact, and they made some surprising discoveries. Lin-4 did not block the activity of lin-14 through the protein it encodes but in a manner never seen before: by direct interaction between the two genes’ RNA strands. These critical RNA molecules also appeared to be extremely small, around 20 nucleotides long. In the meantime Baulcombe was pursuing similar research in plants. His discovery that plant genes could be silenced by the action of tiny RNAs—similar to the worm sequences studied by Ruvkun and Ambros—implied that the same mechanism operates in plants and animals.
In 2000 Ruvkun’s team discovered let-7, another tiny regulatory RNA that shuts down its target gene the same way that lin-4 silences lin-14. They also found that the let-7 RNA sequence had been snipped out of a larger RNA molecule that folds back on itself in a hairpin shape. Later that year Ruvkun published evidence that animals from fish to flies to humans have their own versions of let-7, suggesting that the mechanism operates in all but the most primitive animal species.
In 2001 Ruvkun collaborated with Craig Mello, of the University of Massachusetts, and Andrew Fire, then at the Carnegie Institution, to show that the microRNAs of both lin-4 and let-7 are released from their precursor hairpin RNA molecules by the enzyme Dicer, which is also critical to the RNA interference process that Mello and Fire had discovered and for which they received the 2006 Nobel Prize in Physiology or Medicine.
It now appears that the human genome contains between 500 and 1,000 microRNAs implicated in a broad range of normal and disease-related activities. Researchers have just begun exploring their potential for the diagnosis, prognosis, and treatment of disease. In addition to continuing investigation of RNA’s role in controlling gene expression, Ruvkun’s team studies other mechanisms involved in the development, metabolism, and longevity of C. elegans, including genes involved in the regulation and storage of fat.
Recently, Ruvkun and Ambros also received the Warren Triennial Prize from MGH. Named for John Collins Warren, a cofounder of the hospital, its first surgeon, and the one who performed the first operation on a patient under ether, the award is the hospital’s highest honor for research. The recipients each receive $50,000 and will speak at a celebratory symposium in October.
News & Research
