PhD Studentship: Investigating the role of PRMT5 in breast cancer stem cells and the DNA damage res
- Employer
- Global Academy Jobs
- Location
- United Kingdom
- Closing date
- Jan 31, 2018
View more
- Sector
- Business and Finance, Science, Computer Science and IT, Life Sciences, Cell and Molecular Biology, Chemistry, Biochemistry
- Hours
- Full Time
- Organization Type
- University and College
- Jobseeker Type
- Academic (e.g. 'Lecturer')
Job Details
Fully funded 3-year PhD Studentship starting October 2018.
Despite recent advancements, breast cancer is still a leading cause of cancer mortality. One reason for this is that breast cancer initiation, relapse and metastatic spread is thought to originate from a small population of specialised tumour cells called breast cancer stem cells. Unfortunately, these cells are very hard to drug target as they cycle slower than the bulk tumour mass, have enhanced DNA repair, and are thus more resistant to chemotherapy. Identifying novels ways in which to drug target this cancer-causing population are urgently required.
Dynamic regulation of protein function via post-translational modifications is often deregulated during oncogenesis. Whilst this has long been appreciated for protein phosphorylation, it is becoming increasingly apparent that other less-well characterised protein modifications are equally important. One such modification is arginine methylation catalysed by PRMTs. Surprisingly, although aberrant PRMT5 expression and activity in breast cancer is highly correlative to a poor patient prognosis, the significance and mechanistic understanding of how PRMT5 drives breast cancer pathogenesis is still in its infancy, despite the fact that small molecular inhibitors towards PRMT5 are in phase 1 clinical development.
We have recently made significant in-roads into these critical questions and shown that PRMT5 is an important regulator of double strand break repair via the methylation of RUVBL1 (Clarke et al. Molecular Cell, 2017), and that PRMT5 is required for the maintenance of breast cancer stem cells, both in vitro and in animal models of breast cancer (Chiang et al., Cell Reports, 2017). This PhD project will further investigate the link between PRMT5 and cancer stem cell biology, with a focus on understanding DNA repair mechanisms and the identification of novel stem cell specific PRMT5 substrates. Methodologies used to address these questions will include protein biochemistry, appropriate cell biology assays, microscopy, immunohistochemistry, CRISPR gene knockout and RNA interference in human cancer cell lines, in vitro cancer models, in vivo animal models and quantitative mass spectrometry.
Person Specification
The Davies laboratory is part of the Institute of Cancer and Genomic Sciences and Birmingham Centre for Genome Biology (https://www.birmingham.ac.uk/research/activity/mds/centres/genome-biology/index.aspx), offering the student excellent training opportunities and mentoring. Applicants should have a strong background in cancer biology, DNA repair and protein biochemistry, and be excited to work in a highly dynamic and fast-paced research group. They should be ambitious, hard working and committed to their PhD programme, and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.
Informal enquiries should be directed to Dr. Clare Davies (c.c.davies@bham.ac.uk)
Funding Notes
British and EU nationality applicants are eligible for both the cost of tuition fees and a yearly stipend (at RCUK rate) over the course of the PhD programme.
References
- Clarke, T.L., Sanchez-Bailon, M.P., Chiang, K., et al. (2017). PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination. Molecular Cell.
- Chiang, K., Zielinska, A.E., Shaaban A.M., et al. (2017). PRMT5 Is a Critical Regulator of Breast Cancer Stem Cell Function via Histone Methylation and FOXP1 Expression. Cell Reports
- Auclair, Y. and Richard, S. (2013) The role of arginine methylation in the DNA damage response. DNA Repair.
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