Terry Orr-Weaver, PhD

Member, Whitehead Institute Professor of Biology, MIT 617.258.5251 weaver@wi.mit.edu

Whitehead Member Terry Orr-Weaver investigates the mechanisms that control the sequence of events during which a cell duplicates its DNA and divides in two. Studies in the Orr-Weaver lab have illuminated fundamental aspects of this process, known as the cell cycle, and shed new light on a broad range of diseases caused by breakdowns in cell division, including cancer and certain birth defects [ orr-weaver research 220 kbps QuickTime].

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 the 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. Their studies uncovered dual roles for proteins in transcription and DNA replication.

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). Her research is defining mechanisms by progression through meiosis is developmentally controlled in the oocyte, an essential aspect in the production of an egg that can yield a viable embryo.

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.  In 2007, she was appointed an American Cancer Society Research Professor.  In 2008 she was appointed a senior advisor of the Genetics Society of America and elected president of the National Drosophila Board.

Selected Publications

Vardy, L., Pesin, J. and Orr-Weaver, T. Regulation of Cyclin A protein in meiosis and early embryogenesis. Proc. Natl. Acad. Sci. USA 106: 1838-1843 (2009).

Xie, F. and Orr-Weaver, T.L. Isolation of a Drosophila amplification origin developmentally activated by transcription. Proc. Natl. Acad. Sci. USA 105: 9651-9656 (2008).

Vardy, L. and Orr-Weaver, T.L. The Drosophila PNG kinase complex regulates the translation of Cyclin B. Dev. Cell 12: 157-166 (2007).

Tadros, W., Goldman, A.L., Babak, T., Menzies, F., Vardy, L., Orr-Weaver, T., Hughes, T.R., Westwood, J.T., Smibert, C., and Lipshitz, H.D. SMAUG is the major regulator of maternal mRNA destabilization in Drosophila and is translationally activated by the PAN GU kinase. Dev. Cell 12: 143-155 (2007).

Park, E., MacAlpine, D., and Orr-Weaver, T.L. Drosophila follicle cell amplicons as models for metazoan DNA replication: A cyclinE mutant exhibits increased replication fork elongation. Proc. Natl. Acad. Sci. USA 104: 16739-16746 (2007).

Pesin, J. and Orr-Weaver, T.L. Developmental role and regulation of cortex, a meiosis-specific Anaphase-Promoting Complex/Cyclosome activator.  PloS Genetics 3: e202 (2007).

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