David P. Bartel, PhD

Member, Whitehead Institute Professor of Biology, MIT Investigator of the Howard Hughes Medical Institute 617.258.5287 dbartel@wi.mit.edu

Whitehead Member David Bartel has made major contributions to recent advances in understanding the roles that ribonucleic acid (RNA) plays in contemporary biology and may have played in early evolution.

The Bartel lab was among those to report the existence of hundreds of tiny RNAs, known as microRNAs, which regulate the expression of protein-coding genes in animal and plant cells. Together with their colleagues, they then developed, for both plants and animals, the methodology needed to identify which genes each microRNA regulates. Among other findings, their analyses indicate that well over one third of human protein-coding genes are targets of microRNAs, and that microRNAs, either directly or indirectly, influence a large majority of the mammalian genome. Their experiments focusing on particular microRNAs and targets made major contributions to the understanding of molecular consequences and biological roles of microRNA action, including how microRNAs play important roles in plant development and how a human microRNA helps prevent cancer.

While searching for additional microRNAs, the Bartel lab discovered other types of small regulatory RNAs, including "heterochromatic" siRNAs, which direct DNA silencing. The Bartel group also made significant contributions in developing RNA interference, a powerful biochemical tool that works by blocking the delivery of genetic messages from DNA. Important advances for the new small interfering RNA technique, which extends RNAi to mammalian cells, began in Bartel's laboratory.

In earlier work, Bartel and his colleagues investigated RNA's ability to catalyze reactions and studied how new RNA enzymes (ribozymes) emerge. The group created new ribozymes with enzymatic activities thought to have been required early in evolution, before the emergence of enzymes made of protein. For example, the researchers generated a ribozyme that synthesizes small pieces of RNA, supporting the idea of an "RNA world" during the early evolution of life that featured RNA self-replication. Further work in this area may point toward the eventual synthesis of minimal forms of life based on RNA.

Bartel joined Whitehead Institute in 1994 as a Whitehead Fellow, following the completion of his PhD at Harvard University. In 1996 he was appointed an Associate Member of Whitehead and assistant professor of biology at MIT. Bartel is now a Howard Hughes Medical Institute Investigator, a Member at Whitehead and professor at MIT.

Selected Publications

Mayr, C., Hemann, M.T., and Bartel, D.P. (2007). Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 16: 1576-1579

Axtell, M.J., Jan, C., Rajagopalan, R., and Bartel, D.P. (2006). A conserved trigger for siRNA biogenesis in plants. Cell 127: 565-577

Ruby, J.G., Jan, C., Player, C., Axtell, M.J., Lee, W., Nusbaum, C., Ge, H., and Bartel, D.P. (2006). Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in Caenorhabditis elegans. Cell 127: 1193-1207

Farh, K.K., Grimson, A., Jan, C., Lewis, B.P., Johnston, W.K., Lim, L.P., Burge C.B., Bartel, D.P (2005). The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science 310: 1817-1821.

Lewis, B.P., Burge, C.B., and Bartel, D.P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120: 15-20.

Yekta, S., Shih, I., and Bartel, D.P. (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science 304: 594-596.

Reinhart, B.J. and Bartel, D.P. (2002). Small RNAs correspond to centromere heterochromatic repeats. Science 297: 1831.

Rhoades, M.W., Reinhart, B.J., Lim, L.P., Burge, C.B., Bartel, B., and Bartel, D.P. (2002). Prediction of plant microRNA targets. Cell 110: 513-520 .

Lau, N.C., Lim, L.P., Weinstein, E.G., and Bartel, D.P. (2001). An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294: 858-862.

Johnston, W.K., Unrau, P.J., Lawrence, M.S., Glasner, M.E., and Bartel, D.P. (2001). RNA-catalyzed RNA polymerization: Accurate and general RNA-templated primer extension. Science 292: 1319-1325.

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