Recent genome-wide association studies for coronary artery disease (CAD) have identified an enrichment of loci linked with vascular pathways. The majority of variants are non-coding and likely to function through alterations in gene expression. Through analysis of vascular accessible chromatin and bioinformatics we have identified potentially functional CAD variants. The aim of this project will be to examine these variants for effects on gene expression and their role in vascular remodelling. The ultimate goal is to identify novel therapeutic targets to complement existing CAD treatments.
This studentship will use the high-throughput massively-parallel reporter assay (MPRA) to examine effects of variants on gene expression in vascular cells. From prioritised variants, the student will perform genome-editing using CRISPR-Cas9 based technology to create isogenic cell lines. These will be used to examine the role of individual variants in gene expression and cellular processes related to angiogenesis, such as cell invasion, proliferation and tube formation using in vitro models. The project is primarily laboratory-based, although development of computational skills will be encouraged to analyse high-throughput sequencing data.
The student will gain skills in cutting-edge technologies at the forefront of genomics and the project is expected to result in high-impact findings. The successful candidate will be supported by a dedicated team of laboratory-based and computational scientists along with expertise from collaborators, and will develop key skills to progress either in academia or industry.
For informal inquiries please contact Prof Deloukas [Email Address Removed] or Dr Andrew Smith [Email Address Removed]
Applications should be sent directly to QMUL admissions via this link (choosing the category: PhD Full-time William Harvey Research Institute (non-clinical) Semester 3 (April Start)):
https://www.qmul.ac.uk/postgraduate/research/subjects/medicine-william-harvey-research-institute.html
The closing date for applications is Tuesday 12th April 2022, interviews will be thereafter. Start is date 1st June 2022