1997 BSc (Hons), Biological Sciences, University of Wolverhampton
2000 PhD, School of Applied Science, University of Wolverhampton
2000 Postdoctoral Research Fellow, Prof Jim Callow, University of Birmingham
2002 Postdoctoral Research Fellow, Prof Noni Franklin-Tong, University of Birmingham
2006 Postdoctoral Research Fellow, Profs Machesky and Watson, Univ of Birmingham
2008 BHF Research Fellow, University of Birmingham
Platelet and Megakaryocyte Cell Biology, Actin Dynamics, Imaging
Cortactin & HS1Cortactin and HS1 are monomeric actin binding proteins that can promote re-organization of the actin cytoskeleton downstream of many external stimuli. They are important regulators of Arp2/3 complex activity and believed to be involved in promoting lamellipodia formation, invadopodia formation, cell migration, and endocytosis. We are using knockout mouse models for the two proteins to investigate their role in platelet and megakaryocyte formation and function.
The formins are a family of proteins that regulate actin polymerization downstream of Rho-family GTPases. The role of formins in platelets is not well understood and we are using available knockout mouse models to investigate function in platelets and megakaryocytes.
Delivery of imaging probesPlatelets pose an interesting problem for dynamic imaging using fluorescent probes. As they do not possess a nucleus, transient expression of tagged proteins in not an option. Therefore we are investigating ways of delivering imaging probes including permabilisation and pH dependent peptide flipping. We aim to deliver Lifeact, a live cell imaging probe for F-actin, to allow imaging of the actin dynamics of human platelets. Furthermore, in collaboration with researchers in the Physical Sciences of Imaging in Biomedical Sciences (PSIBS) Doctoral Training Centre we are applying these delivery techniques to lanthanide nanoparticles, novel labels which have many applications in light and electron microscopy.
We are applying standard widefield and confocal microscopy as well as TIRF microscopy to studying actin dynamics in live platelets. Using a Lifeact-GFP mouse model and the probes described above, we aim to dissect out early events in platelet spreading including understanding the role of the actin nodule, a novel actin structure we recently identified that is present in platelets during early spreading
In collaboration with Computer Sciences and through the PSIBS Doctoral Training Centre we are developing methods for analyzing platelet function. For example, we are using image analysis to automatically track actin nodules in spreading platelets. Using this we hope to elucidate their role in actin dynamics as platelets progress from initial adhesion to fully spread. Furthermore, we aim to simultaneously track integrins during spreading to allow the relationship between patterns of actin nodule and surface receptor behavior to be determined.
We are also working on mathematical and computer modeling of Differential Interference Contrast (DIC) microscopy to allow for automated analysis of platelet spreading in real time. Additionally these models will allow us to begin to model platelet spreading in 3D
Mazharian, A., Thomas, S.G., Dhanjal, T.S., Buckley, C.D. & Watson, S.P. (2010) Critical role of Src-Syk-PLCg2 signalling in megakaryocyte migration and thrombopoiesis. Blood. 116(5) pp 793 - 800.
Cullinane. A.R., Straatman-Iwanowska, A., Zaucker, A., Wakabayashi, Y., Bruce, C., Luo, G., Rahman, F., Gurakan, F., Utine, E., Ozkan, T.B., Denecke, J., Vukovic, J., Di Rocco, M., Mandel, H., Cangul, H., Matthews, R.P., Thomas, S.G., Rappoport, J., Arias, I.M., Wolburg, H., Knisely, A.S., Kelly, D.A., Mueller, F., Maher, E.R. and Gissen, P. (2010) Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. Nature Genetics. 42 pp 303 - 312
Senis YA, Tomlinson MG, Ellison S, Mazharian A, Lim J, Zhao Y, Kornerup KN, Auger JM, Thomas SG, Dhanjal T, Kalia N, Zhu JW, Weiss A and Watson SP. (2009) The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis. Blood. 113, 4942-4954. . 113, 4942-4954.
Protty, M.B., Watkins, N.A., Colombo, D., Thomas, S.G., Heath, V.L., Herbert, J., Bicknell, R., Senis Y.A., Ashman, L.K., Berditchevski, F., Ouwehand W.H., Watson, S.P. & Tomlinson, M.G. (2009) Identification of Tspan9 as a novel platelet tetraspanin. Biochem J. 417(1) pp 391-400
Calaminus SD, Thomas SG, McCarty OJ, Machesky LM and Watson SP. (2008) Identification of a novel, actin-rich structure, the actin nodule, in the early stages of platelet spreading. J Thromb Haemost 6: 1944-52.
Thomas SG, Calamius SD, Auger JM, Watson SP and Machesky LM. (2007) Studies on the actin-binding protein HS1 in platelets. BMC Cell Biology 8: 46.
Thomas SG, Huang S, Li S, Staiger CJ and Franklin-Tong VE. (2006) Actin depolymerisation is sufficient to induce programmed cell death in self-incompatible pollen. J Cell Biology 174: 2211-29.
Thomas SG and Franklin-Tong VE. (2004) Self-incompatibility triggers programmed cell death in Papaverpollen. Nature 429: 305-9.pollen. 429: 305-9.