Name of scholarship/program
The differential modification of glycosaminoglycans by VEGFA and VEGFC and consequential effects on GEnC barrier integrity.
Eligibility and other criteria
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 effect 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).
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).
Please contact Dr Becky Foster (http://www.FindAPhD.com/search/EmailEnquiry.aspx?fapjid=44657&LID=177&EAemail@example.com"">firstname.lastname@example.org
) for further details. ***But note the University of Bristol is closed from 29th March to 2nd April 2013 for the Easter break.
Applications should be made online (link below). Please ensure you select FACULTY MEDICAL AND DENTISTRY, programme MEDICINE PhD, and enter the project title in the Research Details section of the form.
This research project has funding attached. Funding for this project is available to citizens of a number of European countries (including the UK). In most cases this will include all EU nationals. However full funding may not be available to all applicants and you should read the full department and project details for further information.
*03 May 2013
Additional information, and important URL
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 . Previous research experience is recommended, especially in the areas highlighted above. A background in animal work would be advantageous, but not necessary.
The stipend starts from Â£19,919 and covers all consumables, with a travel allowance of up to Â£1,000 a year.
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