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Platelet-cell interactions: Platelets beyond thrombosis and haemostasis


School of Biological Sciences

Applications accepted all year round Self-Funded PhD Students Only

About the Project

"Platelets play a key role in the prevention of bleeding following blood vessel damage. In addition to this important role, platelets also impact the pathophysiology of some major health issues such as inflammation, cancer and infection and play a role in normal physiology such as the development of the lymphatic vasculature. These processes involve the direct communication of platelets with other cells types and involves changes in the distribution of receptor ligand interactions which lead to changes in cell behaviour.

In this project you will study how platelets communicate with other cell types, how the communication signals are formed and regulated and how this message tells the cells what to do. The identification of new mechanisms that guide cell behaviour following contact with platelets will help us to develop new ways to treat vascular conditions such as atherosclerosis and pathologies such as cancer and reduced wound healing.

Based in the Institute for Cardiovascular and Metabolic Research, which provides a multidisciplinary interactive research environment for over 30 research groups, this project will provide an excellent opportunity for training in a wide range of basic molecular and cell biology methods including flow cytometry, immunoprecipitation, functional assays such as migration as well as specialist training in conventional and super-resolution microscopy techniques such as confocal and dSTORM.
"

References

"- Navarro-Nunez, L., Pollitt, A. Y., Lowe, K., Latif, A., Nash, G. B., and Watson, S. P. (2015) Platelet adhesion to podoplanin under flow is mediated by the receptor CLEC-2 and stabilised by Src/Syk-dependent platelet signalling. Thrombosis and haemostasis 113, 1109-1120
- Pollitt, A. Y., Poulter, N. S., Gitz, E., Navarro-Nunez, L., Wang, Y. J., Hughes, C. E., Thomas, S. G., Nieswandt, B., Douglas, M. R., Owen, D. M., Jackson, D. G., Dustin, M. L., and Watson, S. P. (2014) Syk and Src family kinases regulate C-type lectin receptor 2 (CLEC-2)-mediated clustering of podoplanin and platelet adhesion to lymphatic endothelial cells. The Journal of biological chemistry 289, 35695-35710
- Gitz, E., Pollitt, A. Y., Gitz-Francois, J. J., Alshehri, O., Mori, J., Montague, S., Nash, G. B., Douglas, M. R., Gardiner, E. E., Andrews, R. K., Buckley, C. D., Harrison, P., and Watson, S. P. (2014) CLEC-2 expression is maintained on activated platelets and on platelet microparticles. Blood 124, 2262-2270
- Borgognone, A., Navarro-Nunez, L., Correia, J. N., Pollitt, A. Y., Thomas, S. G., Eble, J. A., Pulcinelli, F. M., Madhani, M., and Watson, S. P. (2014) CLEC-2-dependent activation of mouse platelets is weakly inhibited by cAMP but not by cGMP. Journal of thrombosis and haemostasis : JTH 12, 550-559
- Finney, B. A., Schweighoffer, E., Navarro-Nunez, L., Benezech, C., Barone, F., Hughes, C. E., Langan, S. A., Lowe, K. L., Pollitt, A. Y., Mourao-Sa, D., Sheardown, S., Nash, G. B., Smithers, N., Reis e Sousa, C., Tybulewicz, V. L., and Watson, S. P. (2012) CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development. Blood 119, 1747-1756
- Severin, S., Pollitt, A. Y., Navarro-Nunez, L., Nash, C. A., Mourao-Sa, D., Eble, J. A., Senis, Y. A., and Watson, S. P. (2011) Syk-dependent phosphorylation of CLEC-2: a novel mechanism of hem-immunoreceptor tyrosine-based activation motif signaling. The Journal of biological chemistry 286, 4107-4116
- Pollitt, A. Y., Grygielska, B., Leblond, B., Desire, L., Eble, J. A., and Watson, S. P. (2010) Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac. Blood 115, 2938-2946"

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