Catherine Pears
Cell Signalling
Co-workers: Duen-Wei Hsu, Rhian Kiely, Amanda Unsworth, Christine Borer
We exploit molecular genetic, biochemical and cell biology techniques to study changes in cell behaviour in the haploid eukaryote Dictyostelium discoideum. Dictyostelium grows as single amoebae. Starvation triggers a developmental life cycle in which amoebae aggregate to form a multicellular structure containing a head of spores supported by a stalk of dead cells. This organism is therefore ideal to study protein kinases involved in regulation of differentiation. Both Cdk8 and Gsk-3 protein kinases are required for correct expression of developmental genes and we are investigating their activation and downstream targets. Modifications of histones associated with developmental genes are implicated in control of expression and we are determining their importance (collaboration with Louis Mahadevan).
Histone modification also plays a major part in DNA damage response and we identified an orthologue of a damage activated kinase, DNA-PKcs, in Dictyostelium. We are now exploiting Dictyostelium genetics to study DNA repair mechanisms (collaboration with Nick Lakin). Characterising these pathways in Dictyostelium aids understanding of these responses in higher organisms. We are investigating the role of protein kinases during activation of human platelets (collaboration with Steve Watson, Birmingham University) with implications for understanding of bleeding disorders and thrombotic disease caused by inappropriate platelet function.
Publications
- Pears, C., Thornber, K., Auger, A., Hughes, C., Protty, M., Grigielska, B., Pearce, A. and Watson, S. (2008). Differential roles of PKC novel isoforms, PKCd and PKCe, in mouse and human platelets. PLoS ONE 3, e3793
- Strmecki, L., Bloomfield, G., Araki, T., Dalton, E., Skelton, J., Schilde, C., Harwood, A., Williams, J.G., Ivens, A. and Pears, C. (2007) Proteomic and micro-array analyses of the Dictyostelium Zak1-GSK-3 signalling pathway reveals a role in early development. Euk. Cell. 6, 245-252
- Strmecki, L., Greene, D. and Pears, C. (2005) Developmental decisions in Dictyostelium discoideum. Dev. Biol. 284, 25-36
- Hudson, J., Hsu, D., Guo, K., Zhukovskaya, N., Liu, P., Williams, J., Pears, C. and Lakin, N. (2005) DNA-PKcs dependent signaling of DNA damage in Dictyostelium discoideum. Curr. Biol. 15, 1880-1885
- Lin, H., Khosla, M., Huang, H., Hsu, D.W., Michaelis, C., Weeks , G. and Pears, C. (2004) A homologue of Cdk8 is required for spore cell differentiation in Dictyostelium Dev. Biol. 271 , 49-58
More Publications...
Research Images
Figure 1: Life cycle of Dictyostelium discoideum
Figure 2: Mature fruiting bodies stained for expression of b-galactosidase driven from a promoter preferentially expressed in the precursors of either stalk (A) or spore (B) cells
Figure 3: Development of parental Dictyostelium cells (i) in comparison with cells in which the gene encoding the kinase Cdk8 has been disrupted (ii)
Figure 4: Time course of human platelet spreading on surface of fibrinogen
Contact:catherine.pears@bioch.ox.ac.uk
Graduate Student and Postdoctoral Positions: Enquiries with CV welcome