Fetal growth restriction (FGR) and pre-eclampsia affect approximately 8% and 3% of human pregnancies respectively. There is currently no cure for either of these complications. FGR is thought to be attributable to placental dysfunction, which has a significant vascular component; this leads to ischaemia-reperfusion of the placental bed and subsequent reduced fetal growth and development.
Pre-eclampsia, which also has a placental component, results in maternal vascular endothelial cell dysfunction leading to dangerously high blood pressure. Strategies to reduce blood pressure/improve end organ perfusion may correct disease-associated vascular dysfunction and so dramatically improve fetal outcomes.
Statins have been successfully used in cardiovascular disease treatment of non-pregnant adults. Statins improve endothelial cell function by cholesterol-dependent and –independent (pleiotropic) effects; the latter are rapid and readily reversible.
Using robust bioassays, this PhD will seek to determine if statins’ pleiotropic effects, induced by short-term application in vitro:
1) Modify vascular function of human uterine (myometrial) blood vessels from normal pregnancy;
2) Rescue vascular function of blood vessels from pregnancies complicated by fetal growth restriction and pre-eclampsia.
This study will also establish, using animal models of pregnancy complications, if short-term maternal statin administration improves maternal vascular function without compromising fetal growth and development. The clinical implications for pregnancy complication intervention are therefore significant.
The project will be conducted within the Maternal and Fetal Health Research Centre, the largest translational placental research group in Europe. The successful candidate will gain from skills training in areas such as wire myography, protein chemistry, animal models/handling and participant recruitment.
Candidates are expected to hold a minimum upper-second (or equivalent) undergraduate degree in a related biomedical/biological science or reproductive health area. A Masters qualification in a similar area would be an advantage.
This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/sponsorship. Annual fee rates for this project, due to commence from September 2016 onwards, are:
*UK/EU nationals: £19, 000
Non-EU nationals: £32, 500
Please direct applications in the following format to Dr Mark Wareing (firstname.lastname@example.org):
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date
• Evidence of funding.
Any enquiries relating to the project and/or suitability should be directed to Dr Wareing. Applications are invited on an on-going basis but early expression of interest is encouraged.
*UK/EU tuition fees are subject to an annual inflationary increase, anticipated to be approximately 2.5% p.a.
Rossoni, L.V., Wareing, M., Wenceslau, C., Al-Abri, M., Cobb, C. & Austin, C.E. (2011). “Acute simvastatin increases endothelial nitric oxide synthase phosphorylation via AMP-activated protein kinase and reduces contractility of isolated rat mesenteric resistance arteries”. Clinical Science Nov 1;121(10):449-58
Dilworth, M.R.,Andersson, I.J., Renshall, L.J., Cowley, E., Baker, P.N., Greenwood, S.L., Sibley, C.P. & Wareing, M. (2013). “Sildenafil Citrate Increases Fetal Weight In A Mouse Model Of Fetal Growth Restriction With A Normal Vascular Phenotype.” PLoS ONE 8(10): e77748. doi:10.1371/journal.pone.0077748
How good is research at University of Manchester in Clinical Medicine?
FTE Category A staff submitted: 136.18
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