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Forces are important in the cardiovascular system, acting as regulators of vascular physiology and pathology. Residing at the blood-vessel interface, endothelial cells are constantly exposed to mechanical forces due to the flowing blood. One of these forces is the frictional force of shear stress that can differ depending on vessel geometry and type. These patterns can range from uniform blood flow to disturbed blood flow. Although we know that endothelial cells can sense and respond differently to different types of flow, the mechanisms by which they sense and respond to blood flow remain a mystery.

Our laboratory has pioneered the studies of endothelial mechanosensing and has championed the use of a multi-disciplinary approach to this scientific problem. The focus of the proposed studentship is to identify mechanisms by which endothelial cells sense and respond to blood flow.  We will focus on identifying pathways that have been shown to be linked to cardiovascular disease and, depending on the interests of the candidate, can adopt a more basic or translational focus.

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

Collins C, Osborne LD, Guilluy C, Chen Z, O'Brien ET, Reader JS, Burridge K, Superfine R, Tzima E. 2014. Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells.Nat Commun,  5pp. 3984.

4

Liu Y, Collins C, Kiosses WB, Murray AM, Joshi M, Shepherd TR, Fuentes EJ, Tzima E. 2013. A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress.J. Cell Biol.,  201 (6), pp. 863-73. -

5

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

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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