We are pleased to be offering a PhD studentship funded by QMUL's Centre for Genomic Health (LSI). The studentship is open to Home/EU applicants.
The Centre for Genomic Health (CGH) brings together the wealth of genomic expertise around the Queen Mary campus to tackle some of the key roadblocks in the field, such as interpreting the non-coding genome. The William Harvey Research Institute is currently the UK’s largest academic pharmacological research institute, with 350 scientists and clinicians from more than 40 nations, and has a long history of training talented scientists for careers in cardiovascular genomics and translational research. We are seeking an outstanding life sciences graduate to work on the Characterisation of allele-specific variation and long-range interactions at the VEGFA locus.
Genome-wide association studies for coronary artery disease (CAD) and related traits have identified many susceptibility loci, where the majority of associated variants are non-coding and their functional mechanisms unclear. This study will apply recently developed methods to characterise functionality of a subset of these non-coding, common CAD-associated variants. Using an assay to identify accessible chromatin (ATAC-seq) to indicate functional elements of the non-coding genome, the regulatory landscape of human endothelial cells will be examined across individuals to determine common variants that alter regulatory potential.
Vascular Endothelial Growth Factor A (VEGFA) is a member of the PDGF/VEGF growth factor family. It is an angiogenic and neurotrophic factor, secreted by endothelial cells, and is known to impact various physiological and disease processes from cancer to cardiovascular disease and to be pharmacologically modifiable. The VEGFA locus will be examined in detail, where nearby variants have been associated with lipid levels, body mass index and coronary artery disease. Following identification of variants that may affect functionality, long-range interactions will be explored using promoter capture Hi-C (CHi-C), a technique that enables characterisation of long-range interactions between gene promoters and distal genomic elements. It is hoped that the target gene of any variant identified by allele-specific ATAC-seq will be characterised by CHi-C. Where strong evidence is found for functional variants at the locus, CRISPR-Cas9 genome-editing will be performed to confirm this, using pluripotent stem cells induced to an endothelial phenotype, followed by examination of allelic effects on gene expression and downstream effects on cell proliferation and other characteristics relevant to CAD.