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William Theurkauf, Ph.D.Academic Role: Professor
Faculty Appointment(s) In:
Other Affiliation(s):
Regulation of mitotic chromosome segregation
Figure LegendMutations in the Drosophila scrambled locus disrupt mitotic actin organization and function. Drosophila embryogenesis is initiated by 13 rapid nuclear divisions that proceed without cytokinesis. During the final four syncytial divisions, when most of the nuclei are in a monolayer at the surface of the embryo, actin (green) associates with membrane furrows that surround the mitotic spindles (red). In scrambled mutant embryos, the actin furrows do not form and interactions between neighboring spindles lead to chromosome segregation errors. To define the molecular mechanisms that drive actin reorganization, we are using genetic and biochemical techniques to identify proteins that function with scrambled during mitotic furrow assembly. Selected publicationsSibon, O. C. M., V. Stevenson and W. E. Theurkauf. (1997). Checkpoint control at the Drosophila midblastula transition. Nature 388, 93-97. Rotation ProjectsProper control of cell division and accurate chromosome segregation are fundamental to cell function and normal development. Chromosome segregation errors lead to birth defects, and abnormal cell division control is associated with essentially all cancers. A major aim of research in the laboratory is to understand cell cycle control and chromosome segregation mechanisms. We use a combination of classical and molecular genetics, high-resolution in vivo imaging, and biochemical techniques to define pathways that control the cell cycle and chromosome segregation in response to environmental insult (DNA damaging agents) and developmental queues. Rotation projects focus on the role of cell cycle checkpoint and tumor suppressor pathways during the earliest stages of embryogenesis, and cell cycle control of actin and microtubule reorganization during mitosis. Through these projects, students gain exposure of the art in vivo imaging and genetic and molecular manipulations of gene function to define pathways controlling cell division and chromosome segregation. Embryonic PatterningEssentially all cells are asymmetric, with structurally distinct surfaces and polarized internal organization. This asymmetry is essential to the specialized functions cells serve within complex multi-cellular organisms . A second area of interest focuses on the mechanisms that establish cellular asymmetry. In Drosophila, the embryonic axes are specified during oogenesis through the asymmetric localization of key morphogenetic molecules within the developing oocyte. We use axis specification in the fly as a model for the processes that establish cellular asymmetry. An intact microtubule network is essential to axis specification in the fly oocyte and to polarization of somatic. We hope to define the molecular functions for microtubules in establishing cellular asymmetry. We are currently using in vivo imaging techniques to directly characterize the microtubule dependent mRNA transport processes that differentiate the anterior and posterior poles of the developing oocyte. In addition, classical genetic and biochemical techniques are used to identify the microtubule motors and associated proteins that mediate mRNA movements to the oocyte poles. Laboratory PersonnelPost-Doctoral Fellows: Beatrice Benoit, Diana Bratu, Saeko Takada, Hanne Varmark Academic BackgroundBill Theurkauf received his BA from Brandeis University in 1980, and his PhD in Biochemistry from Brandeis in 1988. From 1988 to 1993 he was a postdoctoral fellow in the Department of Biochemistry and Biophysics at UCSF, where he was supported by fellowships from the Damon Runyon-Walter Winchell Cancer Research Fund and NIH. From 1993 to 1998, he was a member of the faculty of the Department of Biochemistry and Cell Biology at the State University of New York at Stony Brook. In September 1998, Dr. Theurkauf joined the Program in Molecular Medicine at University of Massachusetts Medical Center as an associate professor in Molecular Genetics and Microbiology.
Office: Bio4 312E
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Accurate mitotic and meiotic chromosome segregation is essential to normal development
and cell proliferation, and defects in chromosome transmission can lead to cancer or
birth defects. A major focus of the laboratory is to understand the mechanisms that
regulate mitotic chromosome segregation. We use the fruit fly Drosophila melanogaster
as our experimental system. The fly supports a unique combination of classical and
molecular genetic studies, high resolution in vivo imaging, and biochemical
approaches. Current studies are directed at understanding the developmental functions
of cell cycle checkpoint pathways, and cell cycle control of actin and microtubule
reorganization during mitosis. A second area of interest is embryonic axis specification.
In Drosophila, the embryonic axes are specified during oogenesis through the
asymmetric localization of key morphogenetic molecules within the developing oocyte. An
intact microtubule network is essential to axis specification, and we hope to define
the molecular functions for microtubules this fundamental developmental process. We are
currently using in vivo imagine techniques to determine the organization and dynamics
of microtubules during oogenesis, and to directly examine cytoplasmic transport and anchoring
of morphogenetic mRNAs within the developing oocyte. In addition, we have started
to biochemically characterize ovarian microtubule motors, with the goal of identifying
the proteins that mediate mRNA movements to the oocyte poles.
55 Lake Avenue North Worcester, MA 01655