Mechanisms underlying the effects of rare non-coding genetic variants on vascular endothelium functions - PhD in Medical Studies (Research England DTP)
Prof A Shore
Dr J Whatmore
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
The growing number of whole genome sequencing data has revealed thousands of rare genetic variants; however, it is not always straightforward to determine which of these variants play a role in any of the pathologies affecting an individual, because the vast majority of the genetic variation occurs outside the coding sequence of a gene.
To prioritise the search of causal variants, we have characterised the genome non-coding space in cells playing a role in cardiovascular disease and thrombosis, to identify elements with regulatory functions: transcriptional enhancers, open chromatin and DNA long range interactions.
The student will use genome editing (CRISPR/Cas9) to generate induced pluripotent stem cells (iPSC) harbouring the genetic variants found in patients, or other forms of CRISPR/Cas9 to modulate the expression of the gene/s targeted by the regulatory element of interest. Engineered iPSC will be differentiated in endothelial cells, using a well-established protocol, and subjected to different functional assays to determine which functions are affected and how these changes influences disease pathophysiology.
Genetic variants have already been selected and you will be participating in the shortlisting. iPSC techniques, genome editing and functional assays are already available in the laboratory.
You will have access to an extremely data rich environment and will become familiar with data analysis, next generation sequencing data, and statistics; as well as several leading-edge laboratory techniques.
This is a 3 year fully-funded PhD studentship. Stipends are at an enhanced rate of £17,059 (2020-21) and all Home/EU tuition fees are covered. Funds will also be available for travel and research costs.