University of Cambridge | Cambridge, United Kingdom
With Gary Ruvkun and Victor Ambros, for their discovery of small RNAs that turn off genes. Their pioneering work initiated a paradigm shift in our perception of the ways genes are regulated, and this insight is making possible major new genetic tools for basic research, and for improving agriculture and human health.
Understanding how DNA and RNA work inside plants and animals has far-reaching implications for combating disease, raising virus-resistant crops and extending the longevity of cells—and people. The genes inside cells churn out proteins to govern all their systems—from how to build cellular structures to whether a cell lives or dies—and for decades RNA was thought merely to assist production of those proteins. The paradigm of that understanding was well-entrenched in the 1990s, before the work of Victor Ambros, Gary Ruvkun and David Baulcombe helped turn it upside-down, showing that the role of RNA had a much wider scope. Through their research, done jointly and in parallel, these scientists discovered tiny strands of RNA some 20 nucleotides long, which could turn genes off and prevent them from functioning—gene "silencing." Their work has set off an onslaught of research to study the breadth of important cellular processes influenced by small RNA.
Born in 1952 David Baulcombe attended Leeds University where he earned a B.S. in botany in 1973. He went on to receive a Ph.D. from the University of Edinburgh in 1977. Baulcombe was a post-doc at McGill University and at the University of Georgia before establishing a research group at the Plant Breeding Institute in Cambridge. In 1988 he joined the Sainsbury Laboratory, where he did much of his world-renowned work. He is moving his laboratory to the University of Cambridge, where he is now a professor of botany.
Baulcombe's interest in plant genetics came from his interest in virus resistance. In the 1990s his group began studying gene silencing since they suspected—and later showed—it was one way a plant could naturally defend itself against viruses. The researchers published a seminal paper in 1999 stating that small RNA strands were associated with several examples of gene silencing, including one related to viral defense. They deduced that the newly discovered small RNAs, now known as small interfering RNAs or siRNAs, guided the silencing to the right targets. Gary Ruvkun and Victor Ambros had previously published on the existence of a similar small RNA strand (an RNA type now called miRNA), but this had not yet gained much attention. Baulcombe's details of this silencing mechanism helped bring the earlier research into the limelight as did Ruvkun's discovery of a second miRNA, published in 2000. Suddenly there was a new, more complex image of how RNA worked. Small RNA's heretofore unknown job inside cells fueled new work to hammer out the details.
Not only did this discovery catalyze research into a whole family of genetic mechanisms, but it also opened the door for unprecedented control over genes. It helped prove a conceptual framework for interpreting, with the Nobel Prize winning work of Fire and Mello who showed that long double-stranded RNA could silence genes, a process called RNA interference or RNAi. A unifying principle soon showed that the long double-stranded RNA was being chopped into small RNAs to guide the silencing. For basic research, using siRNA to shut off a gene is a great way to figure out just what that gene does. The Baulcombe lab has made very important contributions to this by co-opting viruses to shut off specific genes in plant hosts. On a medical level, small RNAs might be the basis of new drugs to silence disease or virus genes. It is this latter area that Baulcombe continues to research, hoping to protect plants from attack. He also studies how silencing directed by RNA affects growth and development.
Baulcombe is a Fellow of the Royal Society and a foreign associate member of the U.S. National Academy of Sciences. His awards include the Royal Medal, the Massry Prize, the MW Beijerinck Virology Prize, the Wiley Prize in Biomedical Science, the Ruth Allen Award and the Kumho Science International Award in Plant Molecular Biology and Biotechnology.
Information as of April 2008