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In all living organisms, the cell cycle must be tightly regulated to ensure that new cells are created only when necessary and have an accurate copy of DNA to function normally. Once DNA has been replicated-the first part of cell duplication-the cell must then divide in two. The Orr-Weaver lab is exploring the mechanisms by which the cell cycle is coordinated with developmental events.
Orr-Weaver uses fruit flies, which share many genetic similarities with humans[ model organisms 220 kbps QuickTime], to identify proteins critical for accurate DNA replication and partitioning of chromosomes to produce two identical daughter cells. She and her colleagues have developed systems for identifying control proteins and determining their specific roles within the cell.
The Orr-Weaver lab isolated a protein that provides the crucial switch to initiate DNA replication in eukaryotes, including humans. The group defined a new role for two proteins implicated in the majority of human cancers by showing they interact directly with the DNA replication machinery. In addition, the lab has identified regulatory genes that help dictate when a cell should start dividing and when it should stop.
In parallel studies, the Orr-Weaver lab has made major advances in deciphering the complex regulatory system that orchestrates meiosis, the cell division process that creates eggs or sperm. Two proteins she discovered help ensure proper partitioning of chromosomes during meiosis (improper partitioning is a major cause of human birth defects).
In addition to being a Member of Whitehead Institute, Orr-Weaver is a professor of biology at MIT. She came to Whitehead Institute and MIT in 1987, and held the Latham Family Career Development Chair from 1991 to 1994. Orr-Weaver received her PhD in biological chemistry from Harvard University in 1984, and was named a Jane Coffin Child Memorial Fund Fellow in 1984 and a Searle Scholar in 1988. She has served as chair of the Scientific Advisory Committee of the Damon Runyon Cancer Research Foundation and president of the Genetics Society of America. In 2006, she was elected a Fellow of the American Academy of Microbiology and a member of the National Academy of Sciences.
Selected Publications
Lee, L. A., Lee, E., Anderson, M.,A., Vardy, L., Tahinci, E., Ali, S.M., Kashevsky, H., Benasutti, M., Kirschner, M.W., Orr-Weaver, T. (2005). Drosophila genome-scale biochemical screen for PAN GU kinase substrates identifies Mat89Bb as a novel, conserved regulator of the cell cycle and development. Dev. Cell 8: 435-442.
Clarke, A.S., Tang, T. T.-L., Ooi, D. L.-Y., Orr-Weaver, T. (2005). POLO kinase regulates the Drosophila centromere cohesion protein MEI-S332. Dev. Cell 8: 53-64.
Lee, J. Y., Dej, K. J., Lopez, J. M., Orr-Weaver, T. (2004). Control of centromere localization of the MEI-S332 cohesion protection protein. Curr. Biol. 14: 1277-1283.
Dej, K. J., Ahn, C., Orr-Weaver, T. (2004). Mutations in the Drosophila condensin subunit dCAP-G: defining the role of condensin for chromosome condensation in mitosis and gene expression in interphase. Genetics 168: 895-906.
Claycomb, J., Benasutti, M., Bosco, G., Fenger, D. D., Orr-Weaver, T. (2004). Gene amplification as a developmental strategy: Isolation of two developmental amplicons in Drosophila. Dev. Cell 6: 145-155.
Ivanovska, I., Lee, E., Kwan, K. M., Fenger, D. D., Orr-Weaver, T. (2004). The Drosophila MOS homolog is not essential for meiosis. Curr. Biol. 14: 75-80.
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