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Pregnancy-specific glycoproteins in complicated pregnancies

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  • Full or part time
    Dr Myers
    Prof Westwood
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

There are known differences in pregnancy-specific glycoproteins (PSGs) in early pregnancy plasma from women who subsequently develop pre-eclampsia. PSGs are a highly conserved group of proteins secreted throughout pregnancy. Their biological role is unknown, although they are hypothesised to inhibit platelet aggregation.

Study of specific PSGs has been hampered by the lack of reagents specific to members of this protein family. However, we have developed a mass spectrometry (MS) method which allows individual PSGs to be quantified in biological samples, this will be used to investigate the role of PSGs in healthy and complicated pregnancies.

Our hypothesis is that the regulation and/or secretion of PSGs is associated with abnormal placental development and contributes to the development of pre-eclampsia.

Objectives:

- Develop MS assays to measure all members of the PSG protein family

- Determine levels of PSGs in early pregnancy plasma from women who subsequently develop pregnancy complications

- Use ex vivo models (placenta explants) to study the regulation of PSG secretion

- Correlate PSG secretion with other proteins known to be associated with abnormal placental development

- Explore the physiological role of PSGs using platelet activation and other cell interaction assays

The project will combine advanced mass spectrometry and proteomics techniques with cell culture and molecular biology methods. In addition, external collaboration with Dr Tom Moore’s laboratory (UCC) will develop in vitro techniques to explore platelet activation and immunological interactions between PSGs and maternal cells.

The role of PSGs in normal and complicated pregnancy is poorly understood. These proteins clearly have an important function at the maternal-fetal interface and their dysregulation is likely to contribute to the development of important pathological consequences. They may serve as important markers of subsequent pregnancy complications and also provide opportunity for the development of novel therapeutic strategies for pre-eclampsia and other placental diseases.

The project will be conducted within the Institute of Human Development, one of the UK’s leading centres for maternal and fetal research. The successful candidate will benefit from training in several cross-cutting skills, combining biochemistry and advanced analytical chemistry and omics techniques with both in vitro models of primary human tissue and clinical plasma samples.

Candidates are expected to hold a minimum upper-second (or equivalent) undergraduate degree in a related biomedical/biological science, reproductive health or analytical chemistry. 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 Jenny Myers ([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 Myers. Applications are invited on an on-going basis but early expression of interest is encouraged.

http://www.human-development.manchester.ac.uk/staff/JennyMyers
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

Kenny LC, Black MA, Poston L, Taylor R, Myers JE, Baker PN, McCowan LM, Simpson NA, Dekker GA, Roberts CT, Rodems K, Noland B, Raymundo M, Walker JJ, North RA. Early Pregnancy Prediction of Preeclampsia in Nulliparous Women, Combining Clinical Risk and Biomarkers: The Screening for Pregnancy Endpoints (SCOPE) International Cohort Study. Hypertension. 2014; 64(3): 644-52

Myers JE, Thomas G, Tuytten R, Herrewege YV, Djiokep RO, Roberts CT, Kenny LC, Simpson NAB, North RA, Baker PN. Mid-Trimester Maternal ADAM12 Levels Differ According to Fetal Gender in Pregnancies Complicated by Preeclampsia. Repro Sci 2014;DOI: 10.1177/1933719114537713

RT Blankley, C Fisher, M Westwood, RA North, PN Baker, MJ Walker, A Williamson, AD Whetton, W Lin, L McCowan, CT Roberts, GJS Cooper, RD Unwin, JE Myers. A label-free SRM workflow identifies a subset of pregnancy specific glycoproteins as potential predictive markers of early-onset pre-eclampsia. Mol Cel Prot 2013 DOI:10.1074/mcp.M112.026872mcp.M112.026872

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

FTE Category A staff submitted: 136.18

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