About the Project
Applications are invited for a non-clinical PhD studentship at the Cancer Research UK (CRUK) Birmingham Centre.
Many chemotherapies function by promoting DNA damage, however some cancer cells are drug resistant because regions of the genome that express genes that help with DNA repair are amplified. We have identified one such genes that is amplified in 40% of lung cancers as a newly identified substrate of the arginine methyltransferase, PRMT1. Importantly, we have identified a new function for this protein in promoting genome stability. We therefore hypothesise that amplification of this gene protects cancer cells from oncogene-induced replication stress, and that PRMT1-mediated methylation of this protein is an important regulatory component.
This studentship will explore the mechanism by which this gene promotes DNA repair, the significance of arginine methylation as a regulatory post-translational modification, and determine if targeting PRMT1 in combination with other therapies is a way in which to kill cancer cells that have gene amplification.
The student will be combining multiple functional approaches (microscopy, cell biology) with proteomics and mechanistic studies (genetic engineering (CRISPR), immunoblotting, immunoprecipitation, genome-wide DNA/RNA interaction analysis), with translational drug combinations screens, with the aim to identify potential approaches to exploit therapeutically.
The Arginine Methylation and Cancer Pathogenesis Laboratory (https://www.claredavieslab.org/) is a dynamic research group within the CRUK Birmingham Centre, and explores the role of PRMTs for cancer initiation, progression and drug resistance (Jarrold and Davies; (Trends Mol. Med. 2019); Clarke et al., (Mol. Cell, 2017); Chiang et al., (Cell Rep. 2017)). Our aim is to ascertain new ways in which to treat cancer and identify patients that will benefit from PRMT-directed therapies. We take a multi-disciplinary approach that enables detailed mechanistic understanding coupled with translational potential through the use of in vitro and in vivo cancer models, with a particular focusing on understanding how PRMTs support the DNA damage response and mediate epigenetic gene expression.
The deadline for applications is 12th March 2021. Successful applicants will have experience in laboratory research, and will be highly motivated and ambitious. They will have a collegiate mind set, and as well as benefitting from the diverse expertise, resources and opportunities the Centre studentship programme has to offer, they will be willing to work in partnership with Centre colleagues to promote and publicise the research of the Centre. As part of this, the studentship will provide opportunities for science engagement activities in the cancer area.
Capitalising on a single biomedical campus comprising the University of Birmingham and key clinical partners including University Hospitals Birmingham, the Centre builds on Birmingham’s integrated scientific and clinical research programmes and aligned clinical trials, which contribute to a cancer research portfolio of ~£25 million per year. The Centre establishes Birmingham as one of the UK’s premier sites for cancer research, and provides an opportunity to deliver internationally significant translational cancer science. Our mission is to catalyse translationally aligned fundamental discovery science in oncology, and novel therapeutic developments originating from this research, contributing to CRUK’s strategic target of increasing cancer survival rates from 50% to 75% within the next 10 years. Linked strategically with Birmingham’s Experimental Cancer Medicine Centre and UoB’s CRUK Clinical Trials Unit (CRCTU), the Centre forms part of a vibrant pathway for genuine bench-to-bedside cancer research. Join the Cancer Research UK Birmingham Centre as a PhD Student and help to make it one of the UK’s most successful sites for translationally oriented cancer research.
Applicants should have a First or Upper Second Class Honours Degree in a relevant subject, and some experience of working in a laboratory. They should have a strong commitment to research, strong interpersonal skills, and a willingness to take part in public engagement activities. Additionally, non-UK applicants must provide evidence that they can self-fund.
How to apply
Informal enquiries should be directed to Dr Clare Davies ([Email Address Removed])
Applications should be directed to Claire Fenlon ([Email Address Removed])
To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees, ideally who have supervised your laboratory research,
but excluding proposed supervisors for the project;
• A personal statement highlighting your research experience/capabilities and your reason for applying for a PhD studentship at the Cancer Research UK Birmingham Centre;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
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