Fully funded PhD Project

Posted on December 17, 2024

Exploiting a unique mouse model to understand how an adverse maternal pregnancy environment leads to stillbirth and intrauterine growth restriction

Centre for Reproductive Health, University of Edinburgh, Edinburgh, Scotland, UK   

Supervisory Team: Prof N Gray, Dr Matt Brook, Dr Kayhee Hor, Dr Rosie Townsend

About the project

Annually around 2.6 million babies are stillborn which, in the UK, is defined as the loss of a baby after 24 weeks’ gestation. Devastatingly, women whom have had a stillbirth are 5 times more likely to suffer another. Intrauterine growth restriction (IUGR), where foetal growth potential is not achieved in the womb, is a significant risk factor for stillbirth, neonatal death and also impacts childhood (e.g. neurological/behavioural issues) and adult (e.g. cardiometabolic) health. This spectrum of pregnancy disorders is often thought to stem from issues with the placenta or the mother’s health, with only a minority of stillbirth cases being due to congenital foetal abnormalities. However, the physiological, cellular and molecular pathways underlying stillbirth remain poorly understood, in part due to a lack of appropriate animal models.

Excitingly we uncovered in mice that knocking-out an RNA-binding protein, from a well-known family of post-transcriptional regulators, unexpectedly recapitulates key features of this spectrum of pregnancy disorders: IUGR, late gestational mortality and an altered foetal-placental ratio, an indicator of poor placental function. As we have established this is due to an inability of these mice to maintain a healthy pregnancy, this model provides a unique opportunity to uncover the maternal causes of stillbirth/IUGR.

Using this exciting model, we have uncovered pregnancies in these mice show key metabolic and growth factor differences in the foetuses, volumetric changes in the functional layers of the placenta, and multiple sub-clinical changes in maternal physiology.

Building on this important unpublished work, we seek an enthusiastic student to exploit our powerful model, to answer critical knowledge gaps in the maternal origins of stillbirth/IUGR. Using mouse genetics and a wide range of in vivo physiology techniques they will initially probe how the changes we have uncovered contribute to these adverse pregnancies, with particular focus on critical metabolic and cardiovascular adaptations to pregnancy. A combination of cutting-edge in vivo, ex-vivo and in vitro approaches can then be employed to provide a detailed understanding of the underlying dysfunctional cellular and molecular pathways.

The knowledge gained will provide fundamental insights into the pathways underlying healthy pregnancy as well as the biological roles of the RNA-binding protein. The overall aim of the project is to create knowledge that can be exploited to develop early diagnostics to identify adverse pregnancies allowing intervention, and in the longer-term for novel therapeutic avenues.

PhD programme in Reproductive Health and Science

This 3.5 year studentship program is based at the Centre for Reproductive Health (CRH) within the Institute for Regeneration and Repair (IRR).

 Students will receive cross-disciplinary training aimed at equipping graduates with skills to drive future research developments in reproductive science and health. At the end of 3 years of PhD study, 0.5 years of funding is available to support approved activities that enable student career progression.

Applicants are encouraged to contact Prof. Nicola Gray [email protected]

Students will benefit from the world-leading research at the CRH, which is led by a combination of non-clinical and clinician scientists. Students will be integrated into the broader CRH PhD programme, providing exposure to diverse aspects of Reproductive Health, and be embedded in the IRR’s Postgraduate Training Framework. Students will have access to state-of-the-art research facilities at IRR and the wider University, and benefit from a broad range of training opportunities which are available across The University of Edinburgh campus. Training in Edinburgh: Edinburgh has a wide range of training opportunities, from those aimed at acquisition of general research skills and transferable skills (Institute for Academic Development) to advanced training courses in specific areas (e.g. image analysis, analysis of transcriptomic data sets).

Full eligibility criteria and further details about the PhD studentships and application process as below, but these studentships are only to support non-clinical students. University of Edinburgh adheres to equality, diversity and inclusion principles.

This opportunity is open to UK and international students and provides funding to cover stipend (maintenance allowance at UKRI rate, which was £19,237.00 for 24-25 and tbc for 25-26) and tuition fees. Applicants are expected to have a good honours degree in the sciences at least UK level of 2.1 or the equivalent from non-UK universities and must meet the English language entry requirements. A Master’s degree in a relevant life sciences subject would be an advantage.

HOW TO APPLY

Required

•   Personal statement (1 page in total) covering why you want to apply for a specific project(s), how your career to date has prepared you to do this PhD, and how gaining this PhD will meet your long-term career goals.

•   Curriculum Vitae (maximum 2 pages)

•   Two academic references using PhD programme reference form - CRH 2025, submitted by the referee by the deadline

Optional

Where applicable 0.5 extra pages can be used to explain any exceptional circumstances that may have affected academic performance to date, non-linear career paths, or any other information we may find useful in ensuring adherence to the principles of equality, diversity and inclusion - This is optional and it is anticipated that the many applicants will not need to provide this additional document.

Applications should be sent to Aga Wysocka [email protected]

Interviews

Interviews will be in the format of a 7 min presentation by the applicant on a previous/on-going research project that showcases skills and knowledge.

This will then be followed by questions on the presentation and their application. The interview - 45 minutes is taking place on Microsoft Teams.

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Funding Notes

This opportunity is open to UK and international students and provides funding to cover stipend (maintenance allowance at UKRI rate, which was £19,237.00 for 24-25 and tbc for 25-26) and tuition fees.