Biography
- PhD University of Edinburgh, 1991
- Postdoctoral work at Stockholm University and Karolinska Institute, Sweden, 1991-1999
- At University of Bath since January 1999
- Lecturer in Cell Biology since September 2000
- Senior lecturer since September 2011
Current Lab Members
- Dr Joseph Dukes
- Miss Laura Fish (Ph.D student)
Funding
Our research is supported by Cancer Research UK. PhD studentships in the laboratory are funded the BBSRC.
Dr Paul Whitley
Profile
Research interests
My lab is interested in endosomal sorting machineries and the cellular processes in which they are involved. Many eukaryotic cell surface proteins (such as growth factor receptors) are selectively removed from the plasma membrane by endocytosis and then either sorted into late endosomes/multivesicular bodies (MVBs) for degradation or recycled back to the plasma membrane. The fate of endocytic cargoes has implications for cell programming and can influence cellular processes such as the cell cycle, apoptosis, migration and cell fate determination. Defects in endocytic sorting have been linked to a variety of human diseases such as cancer and neurodegeneration.
Much of our research is concerned with the function of the ESCRT machinery which is primarily involved in the formation of MVBs and the selective destruction of membrane proteins. At least three endosomal sorting complexes required for transport (ESCRT-I, II and III) and various membrane lipids (PtdIns(3)P, PtdIns(3,5)P2 and LBPA) have been implicated in the biogenesis of MVBs. We found that one of the ESCRT-III components, charged multivesicular body protein 3 (CHMP3/Vps24) binds selectively to the phosphatidylinositol lipid PtdIns(3,5)P2 in vitro (Whitley et al 2003) and have an interest in the cellular function of this lipid (Dukes et al 2006, Whitley et al 2009). Recent work in the lab has focused on investigating the links between defects in endosomal sorting and cell polarity in mammalian cells. We have demonstrated that in mammalian epithelial cells that depletion of ESCRT proteins results in loss of epithelial sheet organisation and a multi-layered cell phenotype (Dukes et al 2011). As loss of cell polarity is one of the hallmarks of epithelial cancers we are currently investigating potential mechanisms behind the loss of polarity in ESCRT ‘mutant’ cells and other tumour suppressive properties of endosomal sorting proteins in mammalian epithelial cells.
Publications
Koumanov, F., Pereira, V. J., Whitley, P. R. and Holman, G. D., 2012. GLUT4 Traffic through an ESCRT-III-Dependent Sorting Compartment in Adipocytes. PLoS ONE, 7 (9), e44141.
Dukes, J. D., Whitley, P. and Chalmers, A. D., 2012. The pikfyve inhibitor YM201636 blocks the continuous recycling of the tight junction proteins claudin-1 and claudin-2 in MDCK cells. PLoS ONE, 7 (3), e28659.
Chalmers, A. and Whitley, P., 2012. Continuous endocytic recycling of tight junction proteins: how and why? Essays in Biochemistry, 53, pp. 41-54.
Dukes, J. D., Whitley, P. and Chalmers, A. D., 2011. The MDCK variety pack: choosing the right strain. BMC Cell Biology, 12, 43.
Dukes, J. D., Fish, L., Richardson, J. D., Blaikley, E., Burns, S., Caunt, C. J., Chalmers, A. D. and Whitley, P., 2011. Functional ESCRT machinery is required for constitutive recycling of claudin-1 and maintenance of polarity in vertebrate epithelial cells. Molecular Biology of the Cell, 22 (17), pp. 3192-3205.
Whitley, P., Hinz, S. and Doughty, J., 2009. Arabidopsis FAB1/PIKfyve proteins are essential for development of viable pollen. Plant Physiology, 151 (4), pp. 1812-1822.
Bangs, F., Yin, Y., Paton, R., Prescott, A., James, J., Davey, M., Whitley, P., Genikhovich, G., Technau, U. and Briscoe, J., 2009. The developmental mutant talpid3 lacks primary cilia. Mechanisms of Development, 126, S262.
Yin, Y. L., Bangs, F., Paton, I. R., Prescott, A., James, J., Davey, M. G., Whitley, P., Genikhovich, G., Technau, U., Burt, D. W. and Tickle, C., 2009. The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation. Development, 136 (4), pp. 655-664.
Dukes, J. D., Richardson, J. D., Simmons, R. and Whitley, P., 2008. A dominant-negative ESCRT-III protein perturbs cytokinesis and trafficking to lysosomes. Biochemical Journal, 411 (2), pp. 233-239.
