PWe study the roles of protein kinases and phosphatases in regulating the progression through mitosis and meiosis with a particular focus upon the control of centrosome and kinetochore function. Our work uses Drosophila and the mouse as experimental models in order to address fundamental questions in cell biology often in a developmental context. Projects are available in four different areas: - Regulation of the molecular linkage of centromeres to kinetochores through the phosphorylation of CENP-C and of how kinetochore components such as Knl1/Spc105 serve as a regulatory scaffold for spindle assembly checkpoint proteins. - Roles of Greatwall protein kinase in phosphoarylating Endos to generate an inhibitor of protein phosphatase 2A, so regulating M phase progression. - Regulation of how centriole proteins interact to assemble this 9-fold symmetrical structure and the roles of Polo-like-kinase 4 (Plk4) in controlling this process and thus the onset of centriole duplication. - Although Plk4 is the master regulator of centriole duplication we recently found it is also required for bipolar spindle formation in the oocytes and early embryos of the mouse that lack centrioles. This leads to numerous questions about the partners and substrates of this kinase in female meiosis in mammals. We also address the controls of how centrioles get lost, how they get rebuilt, and the duality of their function in also templating ciliogenesis. rojects are available to study the roles of protein kinases and phosphatases in regualting the progression through mitosis and meiosis.
- Coelho, P.A., Bury, L., Fu, J., Sharif, B., Riparbelli, M.G., Callaini, G., Glover, D.M. and Zernicka-Goetz, M. (2013) Acentriolar spindle formation in the early mouse embryo requires the “centriolar” protein kinase, Plk4 Dev. Cell 27:586-97
- Przewloka, M.R., Venkei, Z., Bolanos-Garcia, V.M., Debski, J., Dadlez, M., and Glover, D.M. (2011) CENP-C is a structural platform for kinetochore assembly Current Biology 21: 399-405 228.
- Dzhindzhev, N., Yu, Q.D., Weiskopf, K., Cunha-Ferreira, I., Riparbelli, M., Rodrigues-Martins, A., Bettencourt-Dias, M., Callaini, G., and Glover, D.M. (2010) Asterless provides a molecular platform for centriole assembly – Nature 467, 714-718