Genome integrity is threatened by exogenous and endogenous sources of DNA damage, and DNA repair systems therefore form a crucial barrier to tumour formation. DNA double-strand breaks (DSBs) cause chromosomal rearrangements and cell death, and as such the capacity to repair DSBs caused by therapeutic radiation or treatment with DNA-damaging chemotherapies is a major determinant of cancer cell survival and patient outcome. Recently, research has focused on the development of novel strategies to sensitise cancer cells to chemotherapy, and the implementation of novel personalised medicine approaches to improve patient outcomes.
Cancers adapt to grow in adverse conditions such as nutrient and oxygen-poor environments, sensing nutrients such as amino acids through the oncogenic kinase mTORC1, which coordinates nutrient status with growth and metabolism. Small molecule inhibitors of both mTOR and DNA repair enzymes are currently in clinical trials for the treatment of multiple cancers. It is therefore important that we further our understanding of how cells sense nutrients and repair DNA – and integrate these two processes.
There is considerable established interplay between components of cellular nutrient sensing and DNA repair mechanisms, although the significance of these associations remains unclear. We have identified a novel protein complex with dual roles in regulation of both DNA repair and mTORC1-dependent nutrient sensing, and we hypothesize that this complex acts as a signaling hub to integrate these two essential processes.
The successful student will work under the supervision of Dr Chris Staples to generate CRISPR-Cas9 knockout cell lines lacking members of this important new protein complex. They will then analyse the nutrient sensing and DNA repair capacity of the null lines generated, employing confocal microscopy and proteomic approaches to uncover the molecular mechanisms underpinning their function.
The expected start date is January 2020. To apply please send a CV and covering letter to Dr Chris Staples at [email protected] and please cc to Penny Dowdney [email protected] Do feel free to contact Dr Staples via email to discuss the project further, if you are interested.
Knowledge Economy Skills Scholarships (KESS 2 - http://kess2.ac.uk/) is a pan-Wales higher level skills initiative led by Bangor University on behalf of the HE sector in Wales. It is part funded by the Welsh Government’s European Social Fund (ESF) convergence programme for West Wales and the Valleys.
Due to ESF funding, eligibility restrictions apply to this scholarship. To be eligible, the successful candidate will need to be resident in East Wales on University registration, and must have the right to work in the region on qualification.