Newswise — Columbia University will award the 2009 Louisa Gross Horwitz Prize to longtime collaborators Victor R. Ambros, Ph.D. and Gary Ruvkun, Ph.D., for their discovery of microRNAs (miRNAs) – small molecules that are critical to gene regulation. The awardees will give lectures about their discovery on November 17 at Columbia University (details below) – the lectures will be followed by an awards ceremony to mark this honor.
MicroRNAs are small molecules of RNA – single-strands of genetic material – which can regulate the expression of many genes. They were completely unknown before Dr. Ambros identified the first miRNA in the nematode worm C. elegans in 1993. Then in 2000, Dr. Ruvkun discovered a second microRNA in C. elegans and many other species, including humans – illuminating to scientists that miRNAs were not unique to C. elegans, as had been thought. It now appears that the human genome contains between 500 and 1,000 miRNA genes. Today these molecules are implicated in a broad range of normal and disease-related activities, and they have become important research targets for diseases including cancer, heart failure and diabetes.
“It is our privilege to award the 2009 Horwitz Prize to Drs. Ambros and Ruvkun, as recognition for their pioneering work in gene regulation,” said Lee Goldman, M.D., executive vice president of Columbia University and dean of the faculties of health sciences and medicine at Columbia University Medical Center. “Their body of work illustrates the importance of collaboration in science – often a vital intellectual process that is not always visible.”
“The knowledge these two scientists have given us about microRNAs and the role they play in gene regulation has laid the foundation for important scientific research and the potential for major breakthroughs in diseases that are among the most serious that our population faces. Their work also shows how fundamental genetic research leads, often unexpectedly, to profound applications that can benefit humans,” said David Hirsh, Ph.D., executive vice president for research at Columbia University.
Collaboration of Drs. Ruvkun and Ambros Leads to RNA Discovery
“The selection of Victor Ambros and Gary Ruvkun for this year’s Horwitz Prize recognizes their scientific contribution on new understandings of our genetic code, our DNA, and how small portions of it may be involved in the formation of cancer and other chronic illnesses, including diabetes,” said Wayne A. Hendrickson, Ph.D., chair of the Horwitz Prize Committee and University Professor of Biochemistry and Molecular Biophysics at Columbia University, and an investigator of the Howard Hughes Medical Institute.
In the early 1980s, Drs. Ruvkun and Ambros were fellows in the Massachusetts Institute of Technology laboratory of Nobelist H. 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 – Dr. Ruvkun at Harvard and Massachusetts General Hospital, and Dr. Ambros at Harvard (he moved to Dartmouth in 1992 and then to the University of Massachusetts in 2008) – they continued collaborating to uncover how the two regulatory genes interact, and they made some surprising discoveries, including that lin-4 did not encode a protein, as expected, but an extremely small, 22-nucleotide, RNA molecule, later dubbed a microRNA. They also discovered that the lin-4 RNA blocked the activity of lin-14 in a manner never seen before.
Since then, Dr. Ambros and others have identified a wide variety of genes for diverse miRNAs in animals and plants, raising new questions about gene regulation and expression. Today, Drs. Ambros and Ruvkun continue their research on miRNA function and gene regulation during development, and are focused on understanding the genetic and molecular mechanisms that control cell division, differentiation and morphogenesis in animals.
“Working with Gary Ruvkun has been one of the most stimulating adventures of my career. I feel incredibly fortunate to have collaborated with Gary for all these years, to have experienced with him the pleasure of discovery, and now to also share with him this prestigious honor,” said Dr. Ambros, professor of molecular medicine at the University of Massachusetts Medical School.
“Even though we have not worked in the same laboratory since the early 1980s, my collaborative relationship with Victor Ambros has remained, and I am so grateful for this,” said Dr. Ruvkun, professor of genetics at Harvard Medical School and Massachusetts General Hospital’s Simches Research Center. “Our discussions have sparked new thinking for me, and have led to discoveries of which I am very proud.”
Brief Biographies on Dr. Victor Ambros and Dr. Gary Ruvkun
Victor Ambros, Ph.D. completed his undergraduate and graduate degrees as well as his postdoctoral research at the Massachusetts Institute of Technology. During graduate school, he worked with David Baltimore, Ph.D., a co-recipient of the 1975 Nobel Prize in physiology or medicine, where he studied the poliovirus genome structure and replication. In 1979, he began his postdoctoral research in the lab of H. Robert Horvitz, who shared the 2002 Nobel Prize in physiology or medicine, where he met Dr. Ruvkun—and they began collaborating on research into the genetic pathways that control developmental timing in C. elegans. After completing his postdoctoral fellowship, in 1984, Dr. Ambros joined the faculty at Harvard where he remained until 1992, when he accepted a faculty position at Dartmouth. He joined the University of Massachusetts Medical School in 2007. Dr. Ambros was elected to the National Academy of Sciences in 2007.
Gary Ruvkun, Ph.D. is a graduate of the University of California, Berkeley and Harvard. He is professor of genetics at Harvard Medical School. Dr. Ruvkun began to work with C. elegans as a postdoctoral student with Nobelist H. Robert Horvitz at MIT and Nobelist Walter Gilbert at Harvard, where he explored the heterochronic genes that control the temporal dimension of development in a collaborative study with Victor Ambros. The work led to the discovery of the first microRNA gene by the Ambros lab, and that the mechanism of microRNA regulation of target mRNAs is post-transcriptional by the Ruvkun lab. A few years later the Ruvkun lab found the second microRNA gene, let-7 and showed that this microRNA gene is conserved across animal phylogeny. Dr. Ruvkun’s team continues to study other mechanisms involved in the development, metabolism, and longevity of C. elegans, including genes involved in the regulation and storage of fat. Dr. Ruvkun was elected to the Institute of Medicine in 2009.
The Louisa Gross Horwitz Prize was established by Columbia University to recognize outstanding contributions to basic research in the fields of biology and biochemistry. Awarded annually since 1967, the prize is named for the mother of Columbia benefactor S. Gross Horwitz. Louisa Gross Horwitz was daughter of Dr. Samuel David Gross, author of “A System of Surgery” and a founder of the American Medical Association. For additional information about the Louisa Gross Horwitz Prize, visit: http://www.cumc.columbia.edu/horwitz.
The 2009 Louisa Gross Horwitz Prize Lectures will be held on Tuesday, Nov. 17. Dr. Ambros will give his lecture, "MicroRNAs in Development and Disease," at noon in the Davis Auditorium (rm. 412), Schapiro Center, 530 W. 120 Street, at Columbia University’s Morningside Campus; and Dr. Ruvkun will give his lecture, "The Roles and Possibilities of Tiny RNAs," at 3:30 p.m. in the Alumni Auditorium, College of Physicians & Surgeons building, 650 W. 168 Street, at Columbia University Medical Center.
For more information about the lectures, visit http://www.cumc.columbia.edu/events/deanlectures/.
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