Investigation Of The Role Of Chromatin Remodelers In Cellular Senescence And Tumor Progression.
Reference : PhD Bill Keyes
Offer publication : Sept. 23, 2016
A funded PhD position is available in the lab of Dr. Bill Keyes. The lab is in the process of relocating from the CRG, Barcelona to the IGBMC, Strasbourg, and the candidate will work full-time at the IGBMC.
Cellular senescence is an important cellular process that restricts tumor growth at the cell-intrinsic level, but which can promote growth through the senescence associated secretory phenotype (SASP), the secretion of a wide variety of proteins by senescent cells. Senescence is also a key driver of aging, through cell intrinsic effects from the accumulation of senescent cells, as well as an accumulated SASP having detrimental effects on tissue function.
Recently, we identified that the p63 gene can promote tumor formation through the inhibition of cellular senescence, leading to the development of Squamous Cell Carcinoma (SCC) in the skin (Keyes et al, Cell Stem Cell, 2011). This has provided a new model in which to study the mechanisms of tumor initiation and progression. In this study, we identified the chromatin-remodeling factor Lsh/Hells as a target gene of p63, which is required for senescence bypass. A PhD project is available to study the molecular role of Lsh/Hells in senescence and tumor formation/progression.
This will involve gene manipulation through knockdown and overexpression in different cellular models of senescence, including oncogene- and irradiation-induced states. The effects on senescence establishment will then be measured using a variety of cell-based, genetic and epigenetic assays. In addition, its expression and functional role will be analyzed in animal models of tumor formation and progression.
- A high motivation to perform basic science research, and a willingness to work hard to achieve results.
- A strong interest in senescence, stem cells, tumor biology and molecular mechanisms.
- To be able to work as part of a team, as well as independently.
- Fluency in English is required.
- Preliminary experience in any aspect of general cell and molecular biology is advantageous, and the work will involve handling mouse models of cancer.
Major publications (last 5 years)
- Storer, M., Mas, A., Robert Moreno, A., Pecoraro, M., Ortells, M.C., Di Giacomo, V., Yosef, R., Pilpel, N., Krizhanovsky, V., Sharpe, J. and Keyes, W.M. (2013) Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell, 155(5), 1119–1130.
- Doles, J., Storer, M., Cozzuto, L., Roma, G. and Keyes, W.M. Age-associated inflammation inhibits epidermal stem cell function. (2012) Genes & Development, 26(19):2144-53
- Keyes, W.M.,* Pecoraro, M., Aranda, V., Vogel, H., Garcia, E.L., Michurina, T., Enikolopov, G., Muthuswamy, S.K. and Mills, A.A.* DNp63a is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis. (2011) Cell Stem Cell, 8(2) 164-176 (* Corresponding authors).
Application Deadline : Dec. 31, 2016