BHF Funded PhD studentship on the role of PHACTR1 in vascular cell behaviour

Applicants are invited for a new British Heart Foundation funded PhD studentship (planned to commence in the autumn of 2017) to study the regulation and function of the PHACTR1 protein in vascular cells.

Atherosclerosis and related cardiovascular pathologies are leading causes of death in the western world, and prevalence is increasing in ageing populations. Current models of disease development posit a complex interplay between dysfunctional VSMCs and ECs with humoral factors and inflammatory cells. The end result is a pro-inflammatory microenvironment that provokes a vicious cycle of disease progression. Interrupting this cycle can slow disease progression and limit pathological intima formation. For example, medications that lower low density lipoprotein (LDL) cholesterol have revolutionized preventive therapy for cardiovascular disease, whereas those that block cell proliferation have ameliorated angioplasty restenosis. However, neither of these advances fully normalizes CV risk and additional treatments are urgently needed.

The PHACTR1 gene is associated with several single nucleotide polymorphisms that associated with increased risk of heart disease. Little is known about how PHACTR1 protein is regulated or how it modulates vascular cell behaviour during the development of vascular disease. Our preliminary data suggests that the location of the PHACTR1 protein in the cell is dependent on changes in the actin cytoskeleton. Signals that block actin polymerisation prevent PHACTR1 entering the nucleus. We hypothesise that this modulates gene expression and cell behaviour.

This new project will use a variety of molecular and cell biology techniques to study the signals that control PHACTR1 cellular localisation and its function in vascular cells. The project offers the opportunity to study in an excellent research environment, in a research institute with world class facilities and resources devoted to understanding the cellular and molecular mechanisms of cardiovascular disease and driving new translational therapies for patients. We have an opportunity available for exceptional candidates with an interest in the areas of vascular biology, cell signalling and gene expression regulation and drug-discovery.

Candidates should have at least a 2:1 BSc in a biological science.

Funding Notes

The project is dependent on successful award of BHF studentship funding. If successful, tuition fees at UK/EU will be covered by the BHF and the student will be awarded a standard BHF stipend (approx. £20k-£23k/pa)

Supervisor: Dr Bond