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Functional coronary artery disease genetics: investigating the role of the candidate gene in models of In vivo cardiovascular disease

Project Description

Despite significant advancements in its treatment coronary artery disease is the leading cause of death in both the UK and world wide, accounting for over 66,000 deaths in the UK each year. Genome wide association studies have enabled us to identify genes which are associated with cardiovascular disease at the level of the whole genome. These novel genes, which are not associated with traditional risk factors, have the potential to identify novel treatment strategies for coronary artery disease. However, the challenge now is to establish the role of these genes in the pathology of cardiovascular disease. The work in my lab aims to establish the role of novel candidate genes in cardiovascular disease.

Working in close collaboration with bioinformaticians we identify novel candidate genes from GWAS implicated loci. Once suitable candidate genes have been identified, we use In vitro cell based assays in primary human cells to established how the loss of the candidate gene alters basic cell functions such proliferation, migration, respiration and the response to physical stimuli such as flow, using state of the art cellular imaging equipment as well as basic molecular biology skills. The information gained from these In vitro studies is then used in a targeted fashion to investigate the role of the candidate gene in models of In vivo cardiovascular disease, in particular the development and regression of atherosclerosis and models of altered vascular function such as vascular injury and ischaemia models.

Doctorial students have the flexibility to focus either on in vitro cell based assays or in vivo models of cardiovascular disease. A typically In vitro project would involve investigating the expression profile gene of interest in tissue (e.g. arteries with or without atherosclerosis and cells (e.g endothelial cells, vascular smooth muscle cells and inflammatory cells) implicated in coronary artery disease. This would be followed by assessment of the consequences of loss or gain or function of the gene on cell function. It is not anticipated that within the time of the project that detailed in vivo analysis of the gene of interest would be achievable. However, if the student was interested there maybe the scope to extend this project to in vivo studies. In a typically in vivo project, the student will assess the how loss or gain of function of the candidate gene alters vascular function. We will evaluate physiological parameters such as blood pressure and contractile and dilator function of blood vessels before going on to investigate the role of the candidate gene in vascular pathology using models of atherosclerosis and vascular injury.

This DPhil will be based in the Division of Cardiovascular Medicine at the Welcome Centre for Human Genetics. We are part of a wider scientific community with expertise in Cardiovascular Disease allowing for collaborative work with other senior scientist. By the end of this project the candidate will have developed a wide range of laboratory skills such as molecular biology techniques (protein and RNA analysis), cell culture techniques and In vivo models of cardiovascular disease. Training in scientific techniques as well as scientific presentation and writing will be given throughout the project.

As well as the specific training detailed above, students will have access to high-quality training in scientific and generic skills, as well as access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Funding Notes

Our main deadline for applications for funded places has now passed. Supervisors may still be able to consider applications from students who have alternative means of funding (for example, charitable funding, clinical fellows or applicants with funding from a foreign government or equivalent). Prospective applicants are strongly advised to contact their prospective supervisor in advance of making an application.

Please note that any applications received after the main funding deadline will not be assessed until all applications that were received by the deadline have been processed. This may affect supervisor availability.

How good is research at University of Oxford in Clinical Medicine?

FTE Category A staff submitted: 238.51

Research output data provided by the Research Excellence Framework (REF)

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