PhD studentship The differential modification of glycosaminoglycans by VEGFA and VEGFC and consequential effects on GEnC barrier integrity



Faculty of Medicine and Dentistry

This is a 3yr non-clinical PhD studentship directly funded by the British Heart Foundation and is open to home/EU students only (unless willing to self fund the difference in fees). An undergraduate degree with a minimum of a 2:1 is required or an MSc with merit or distinction and previous research experience is recommended, especially in the areas highlighted below. A background in animal work would be advantageous, but not necessary.

The stipend starts from £19,919 and covers all consumables with a travel allowance of up to £1000 a year.

The endothelial sugar coating (glycocalyx) that lines all blood vessels (the vascular system) is composed of negatively charged glycoproteins (glycosylated proteins), proteoglycans (core proteins with glycosaminoglycan side-chains) and absorbed plasma proteins. The glycoclayx mediates vessel responses to flow, attenuates inflammatory cell adhesion and regulates vessel leakiness, allowing the free passage of water and small molecules but restricting the passage of larger proteins. Glycocalyx shedding is associated with the progression of inflammatory conditions, ischaemia reperfusion injury, atherosclerosis, and complications of type 1 and type II diabetes. Thus, the glycocalyx is critical for vascular function including permeability.

Albumin loss into the urine (microalbuminuria) reflects damage to the kidney microvascular (the glomerulus) and can be associated with both glomerular endothelial (GEnC) glycocalyx loss and general endothelial dysfunction. Vascular endothelial growth factor (VEGF) A regulates vessel permeability and overactivity causes leaky vessels and albuminuria. In cell culture VEGFA increases GEnC protein permeability whereas VEGFC reduces it and they have differential effects on the glycocalyx. This studentship will address how VEGFs modify the GEnC glycocalyx, whether this leads to a direct affect on GEnC barrier function and whether VEGFC can protect against the VEGFA associated glycocalyx changes. It will utilise podocyte-specific inducible VEGFA/C overexpressing mice and our unique human conditionally immortalised (ci)GEnC. Methodology includes sterile tissue culture technique, imaging including fluorescence microscopy and electron microscopy, sophisticated disaccharide chromatography analysis, urine and blood biochemical analysis, mRNA (real time PCR) and protein analysis (Western blotting), and functional in vitro assays (labelled albumin passage across monolayers).

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Please contact Dr Becky Foster ([email protected]) for further details or follow link to website: http://www.bristol.ac.uk/clinical-sciences/research/renal/

Application process Applications for this position are to be made using the on-line application http://www.bristol.ac.uk/pg-howtoapply. Please select ‘Medicine PhD’ in the Programme Choice section and cite the title of the studentship in the Research Details and Funding sections of the form.

The closing date for this studentship is Friday 3rd May with interviews to be held within a fortnight of the closing date. The successful candidate may begin from 1st July 2013 (negotiable).

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