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Assessment of novel drug interventions on vascular reactivity and syncytiotrophoblast function in fetal growth restriction

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  • Full or part time
    Dr Wareing
    Prof Sibley
  • Application Deadline
    Applications accepted all year round

Project Description

Fetal growth restriction (FGR) affects approximately 8% of human pregnancies; there is currently no cure for this important complication. FGR is thought to be attributable to placental dysfunction, which has significant vascular (leading to ischaemia-reperfusion of the placental bed) and transport (syncytiotrophoblast malfunction leading to aberrant nutrient uptake) components. Reduced fetal growth and development is a direct result. Strategies to improve blood flow within the placental unit or rescue transport capacity may correct disease-associated dysfunction and so dramatically improve fetal outcomes.

We have previously utilized a number of drugs (e.g. sildenafil citrate) and nutraceuticals (e.g. beetroot juice) in mouse models of pregnancy and noted improved pregnancy outcomes (e.g. increased fetal weight; improved endothelial function). This PhD project will further test these and other novel therapies using human paradigms to determine treatment efficacy.

Using robust bioassays, we will determine if drug/nutraceutical application in vitro:
- Modifies vascular and syncytiotrophoblast function of human term and 1st trimester placental tissue;
- Improves vascular and syncytiotrophoblast function of human term placental tissues from pregnancies complicated by fetal growth restriction

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, placental explant culture, protein expression 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 ([email protected]):
• 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.

http://www.human-development.manchester.ac.uk/staff/MarkWareing
http://www.mhs.manchester.ac.uk/staff/ColinSibley
http://www.human-development.manchester.ac.uk/

Funding Notes

*UK/EU tuition fees are subject to an annual inflationary increase, anticipated to be approximately 2.5% p.a.

References

Desforges, M. & Sibley, C.P. (2010). Placental nutrient supply and fetal growth. Int J Dev Biol 54 (2-3) 377-90. Doi:10.1387/ijbd.082765md

Dilworth, M.R. & Sibley, C.P. (2013). Transport across the placenta of mice and women. Placenta, Suppl S34-9

Cottrell, E.C. & Sibley, C.P. (2015).From Pre-Clinical Studies to Clinical Trials: Generation of Novel Therapies for Pregnancy Complications. J. Mol. Sci., 16, 12907-12924; doi:10.3390/ijms160612907

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

Cottrell, E., Garrod, A., Finn-Sell, S., Wareing, M., Cowley, E., Greenwood, S.L., Lundberg, J., Weitzberg, E., Nihlen, C., Baker, P.N. & Sibley, C.P. (2015) “Maternal Supplementation With Dietary Nitrate Improves Uteroplacental Vascular Function in eNOS-/- Mice”. Reproductive Sciences 22: 182A

How good is research at University of Manchester in Clinical Medicine?

FTE Category A staff submitted: 136.18

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