University of Toronto Biochemistry

	Andrew Wilde Associate Professor B.Sc., UCW Aberystwyth CPC, 1986-1990 Ph.D., University of Bristol, 1990-1994 PDF, University of California, San Francisco (UCSF), 1994-1998 PDF, Dept. of Embryology, Carnegie Institute of Washington, Baltimore, 1998-2001
	Medical Sciences Building, Room 4377 416-946-7714 andrew.wilde@utoronto.ca

Cell Division and Oogenesis

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Research Synopsis

My lab is interested in understanding how cells divide, in particular the signals that spatially coordinate cell division. The production of two viable daughter cells upon cell division is a key requirement during development. Failure to accurately divide a cell can result in the mis-segregation of chromosomes between the two new daughter cells and aneuploidy, a hallmark of tumor cells. To ensure that chromosome segregation happens accurately and efficiently, the individual stages of cell division must occur at the correct time and place within the cell. Many of these processes require the cell to know exactly where the chromosomes are within the cell. For example the microtubule spindle that segregates the chromosomes must form around the chromosomes and the membrane furrow that physically divides the cell must form between the segregated chromosomal masses.

My group is interested in understanding the dynamics of the temporal and spatial signals that coordinate cell division. We have identified one such signal the GTPase Ran. Future works focuses on understanding the extent of this signal and identifying additional signals. To address these questions we use multiple approaches in different model systems including, Xenopus egg extracts, Drosophila embryos and mammalian tissue culture cells. Each system offers a different technical advantage that allows us to ask very precise biological questions. In all systems we use a combination of biochemical and live video microscopy to address the question at hand.

In addition, we are interested in understanding the physiological changes the cell undergoes in preparation for and during cell division. To identify these changes we use Xenopus oocyte maturation as our model where an oocyte matures into an egg. Using proteomic and genomic approaches, we identified many changes during oocyte maturation. Our future work is directed to understanding how these changes prepare the oocyte for fertilization, cell division and early development.

Selected Publications

Moss, D.K, Wilde, A. and Lane, J.D. (2009) Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase Journal of Cell Science 122:644-655.

Wilde A. and Zheng Y. (2009) Ran out of the nucleus for apoptosis. Nature Cell Biology 11:11-12.

Silverman-Gavrila, R.V., Hales, K.G. and Wilde, A. (2008) Anillin-mediated Targeting of Peanut to Pseudocleavage Furrows Is Regulated by the GTPase Ran. Molecular Biology of the Cell 19:3735–3744.

Wilde, A. (2006) 'HURP on' we're off to the kinetochore! Journal of Cell Biology 173:829-831.

Silverman-Gavrila, R. and Wilde, A. (2006) Ran is required before metaphase for spindle assembly and chromosome alignment and after metaphase for chromosome segregation and spindle midbody organization. Molecular Biology of the Cell 17:2069-2080.

Hayashi, I. , Wilde, A., Mal, T.K., Ikura, M. (2005) Structural Basis for the activation of microtubule assembly by the EB1 and p150Glued Complex. Molecular Cell 19:449-460.

Bakal CJ, Finan D, Larose J, Wells CD, Gish G, Kulkarni S, Desepulveda P, Wilde A, Rottapel R. (2005) The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis. Proc Natl Acad Sci U S A. 102:9529-9534.

Trieselmann, N, Armstrong, S., Rauw, J. and Wilde A. (2003) Ran modulates spindle assembly by regulating a subset of TPX2 and Kid activities including Aurora A activation. Journal of Cell Science 116:4791-4798.

Trieselmann, N. and Wilde, A. (2002) Ran localizes around the microtubule spindle in vivo during mitosis in Drosophila embryos. Current Biology 12:1124-1129.

Wilde, A., Lizarraga, S.B., Zhang, L., Wiese, C., Gliksman, N.R., Walczak, C.E. and Zheng, Y. (2001) Ran stimulates spindle assembly by changing microtubule dynamics and the balance of motor activities. Nature Cell Biology 3:221-227.

Wiese, C., Wilde, A., Moore. M. S., Adams, S. A., Merdes, A. and Zheng, Y. (2001) Role of Importin- b in coupling Ran to downstream targets in microtubule assembly. Science 291:635-656.

Zhang, L., Keating, T. J., Wilde, A. Borisy, G.G. and Zheng, Y. (2000) The role of Xgrip210 in g -tubulin ting complex assembly and centrosome recruitment. Journal of Cell Biology 151:1525-1535.

Wilde A. and Zheng Y. (1999) Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. Science 284:1359-1362.

Department of Biochemistry
University of Toronto
Toronto, Canada

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