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Cardiovascular disease is a major cause of morbidity and mortality. Blockage of arteries due to gradual development of atherosclerotic plaques can lead to heart attacks and strokes. Although a number of risk factors have been identified that increase the risk of atherosclerosis development, recent years have seen an explosion of interest in the role of haemodynamic (or mechanical) factors as instigators of vascular pathology. The reason for this is because atherosclerosis develops in specific regions of the arteries that are exposed to non-uniform and “disturbed” blood flow patterns. Endothelial cells that line blood vessels are equipped with the exquisite ability to sense and respond to blood flow and initiate pathways that are termed vascular mechanotransduction.

Our group has pioneered the study of vascular mechanotransduction and its role in cardiovascular disease and uses a multi-disciplinary approach to study this. The focus of the proposed studentship is to identify mechanosensitive pathways that are responsible for development of atherosclerosis. The project involves a combination of in vitro and in vivo approaches in a highly collaborative and multi-disciplinary environment. 

Training Opportunities

This DPhil will be based at the Tzima group at the Wellcome Trust Centre for Human Genetics. We are part of a wider scientific community with expertise in cardiovascular biology and the opportunity to be co-mentored and co-supervised by other senior scientists will be made available.  The student will have the opportunity to be exposed to a wide range of techniques ranging from bioengineering (bespoke shear stress and magnetic application apparatus), state-of-the-art microscopy and cell biology, to in vivo models of cardiovascular disease.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

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 support the careers of female students and staff.

Publications

1

Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. 2005. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress.Nature,  437 (7057), pp. 426-31.

2

Mehta V and Tzima E. 2016. Cardiovascular disease: a turbulent path to plaque formation. Nature, 540 (531-532)

3

Chen Z, Givens C, Reader JS and Tzima E. 2017 Haemodynamics regulate fibronectin assembly via PECAM. Sci Rep. 7 (41223)

4

Sweet DT, Chen Z, Wiley DM, Bautch VL, Tzima E. 2012. The adaptor protein Shc integrates growth factor and ECM signaling during postnatal angiogenesis.Blood,  119 (8), pp. 1946-55.

5

Givens C, Tzima E. 2012. S1P1 bridges mechanotransduction and angiogenesis during vascular development.Dev. Cell,  23 (3), pp. 451-2.

6

Sweet DT, Chen Z, Givens CS, Owens AP, Rojas M, Tzima E. 2013. Endothelial Shc regulates arteriogenesis through dual control of arterial specification and inflammation via the notch and nuclear factor-κ-light-chain-enhancer of activated B-cell pathways.Circ. Res.,  113 (1), pp. 32-9.

Research Themes, Tools and Technologies

Supervisor

  • Ellie Tzima
    Ellie Tzima

    Associate Professor of Cardiovascular Mechanotransduction

Key Dates for October 2018 Entry

Application deadline:  12 noon GMT on Monday 8 January 2018

Interviews for shortlisted candidates: Week commencing Monday 22 January 

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How to apply

To apply for a place on the DPhil in Medical Sciences you will need to submit an application using the online application form.

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