About the Project
Programmed cell death is a natural mechanism in our bodies, which serves to eradicate cells which may otherwise form a tumour. Inactivation of these pathways is, therefore, a common event that contributes to cancer progression. Since many standard forms of cancer therapy also utilize these same pathways to kill cancer cells this causes serious problems, which lead to drug resistance.
It is widely considered that the identification and understanding of novel cell death regulators will lead to new ways to kill cancer cells. In this regard, we have undertaken a series of screens for factors, which regulate apoptosis and autophagy – two processes which regulate cell viability. The successful student will use state-of-the-art genomic and proteomic techniques to understand the role played by this factor in cell death regulation. In addition, through the generation of transgenic systems, which lack this factor, analysis will also be made of the gene’s contribution to tumour development and cancer therapy in genetically-modified in vivo models of cancer.
References
Wilkinson, S., O'Prey, J. Fricker, M. and Ryan, K.M. Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity. (2009) Genes & Development. 23(11): 1283-1288.
Long, J.S., Crighton, D., O'Prey, J., MacKay, G., Zheng, L. Palmer, T.M., Gottlieb, E. and Ryan, K.M. Extracellular adenosine sensing – a metabolic cell death priming mechanism downstream of p53. (2013) Molecular Cell. 50(3):394-406
Liu, E.Y. and Ryan K.M. (2012) Autophagy and cancer – issues we need to digest. Journal of Cell Science. 15;125(Pt 10):2349-58
Rosenfeldt, M.T., O'Prey, J., Morton, J.P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T.S., Zheng, L., Ridgway, R., Adams, P.D., Anderson, K.I., Gottlieb, E., Sansom O.J. and Ryan, K.M. p53 determines the role of autophagy in cancer. (2013) Nature 504(7479):296-300
Liu, E.Y., Xu, N., O'Prey, J., Lao, L.Y., Joshi, S., Long, J.S., O'Prey, M., Croft, D.R., Beaumatin, F., Baudot, A.D., Mrschtik, M., Rosenfeldt, M.T., Zhang, Y., Gillespie D.A. and Ryan K.M. (2014) Loss of autophagy causes a synthetic lethal deficiency in DNA repair. Proc. Natl. Acad. Sci. (USA) 112(3): 773-8.
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