Apoptosis or programmed cell death is a tightly regulated intrinsic process of programmed cell death used by cells in all multicellular organisms, including humans, to control tissue homeostasis or to initiate their own death following malfunction or damage beyond repair. Impairment of apoptosis often underlies failure of cancer suppression mechanisms. Furthermore, resistance to chemo- and radiotherapy is directly linked with resistance to apoptosis of the tumour cells. PERP, a plasma membrane protein, regulated by the p53 family of transcription factors, is a novel specific effector of apoptosis, downregulated in many cancer cells that are often particularly aggressive and metastatic.
The aim of this project is to further the understanding of the molecular mechanism of action of the p53 effector protein PERP, specifically identifying and characterizing the dynamics of PERP-interacting proteins and the mechanism of induction and modulating the apoptotic response in cancer cells. In addition, the study will characterize regulatory networks influencing PERP protein interactions and PERP-responsive downstream signaling pathways.
The study will make use of advanced in vitro experimental cell-based models, including inducible, stable and transient expression of proteins of interest, which have already been proved suitable for studying the functional outcomes of PERP targeting and localization. The combination of different cell types and PERP constructs with specific intracellular targeting of PERP allow us an effective characterisation and control of the PERP-mediated pathway.
The student will be trained in a broad range of advanced, state-of-the-art techniques and analyses, combining molecular biological approaches with functional cellular assays. The local and international collaborations (USA, Spain, Thailand, Brazil) will enhance further the training experience, contributing to the transferable skills acquired.
The training will include core laboratory skills such as cell culture, cloning, expression constructs generation, western blotting and luminescence-based assays, DNA and RNA-based analyses including PCR and q-PCR, alongside transfections, immunoprecipitation, live cell imaging, apoptosis cell assays, confocal microscopy.
The broad set of skills developed during this studentship will render the student highly versatile and competitive for a future academic career or a career in industry.
The student will engage into the University of Liverpool’s graduate education programme, and will have both formal and informal training in generic research skills such as critical thinking, literature reviewing, presentation and scientific writing.
The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. We offer a supportive working environment with flexible family support for all our staff and students and applications for part-time study are encouraged. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.
Enquiries to: Professor Luminita Paraoan, Institute of Ageing and Chronic Disease, University of Liverpool. Tel: +44 151 794 9038
http://www.liv.ac.uk/paraoan Email: [email protected]
To apply: please send your CV and a covering letter explaining your interest in the project to Professor Luminita Paraoan ([email protected]
) with a copy to [email protected]
The project is suited to a student with an undergraduate degree or Master’s degree in Life Sciences (Biology, Genetics, Biochemistry, Biomedical Sciences, Cell Biology) or Medicine with an interest in apoptosis, gene expression and regulation and/or cancer cell signalling.
NO funding is attached to this project. The successful applicant will be expected to provide the funding for tuition fees and living expenses plus approximate research costs (bench fees) of between £5,000 and £7,000 per year
Awais R, Spiller DR, White MRH, Paraoan L. (2016) p63 is required beside p53 for PERP-mediated apoptosis in uveal melanoma. Br J Cancer. Advance Online Publication 1 September 2016. doi: 10.1038/bjc.2016.269.
Hallstrom KN, Srikanth CV, Agbor TA, Dumont CM, Peters KN, Paraoan L, Casanova JE, Boll EJ, McCormick BA. (2015) PERP, a host tetraspanning membrane protein, is required for Salmonella-induced inflammation. Cell Microbiol. 17(6):843-59.
Davies L, Spiller D, White MR, Grierson I, Paraoan L. (2011) PERP expression stabilizes active p53 via modulation of p53-MDM2 interaction in uveal melanoma cells. Cell Death Dis. 2:e136. doi: 10.1038/cddis.2011.19