Defining the impact of endometriosis on immune-vascular remodelling in pregnancy.

Endometriosis is a chronic, hormone-dependent inflammatory condition where tissue similar to the lining of the womb (endometrium) grows outside of the uterus. Although pelvic pain and infertility are established symptoms, growing evidence supports an association between endometriosis and adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction and preterm birth¹. The mechanisms that promote poor pregnancy outcomes in endometriosis are not known.

We and others² have identified that androgens, which are a group of sex steroid hormones, are elevated in endometriosis which may impact on endometrial function in pregnancy. Endometrial remodelling is critical for successful establishment and maintenance of pregnancy and deficits in this can lead to adverse pregnancy outcomes and altered health trajectories for the offspring. Our previous work identified that androgens regulate endometrial remodelling by promoting stromal decidualisation and immune-vascular remodelling³ but whether altered androgen signalling in endometriosis can disrupt these key processes has not been determined.

This project will determine how androgens alter endometrial remodelling by using genetic and pharmacological approaches to alter androgen signalling and assess impacts on decidualisation, immune-vascular remodelling and pregnancy outcomes.

This project will utilise reproducible mouse models of endometriosis and pregnancy that we have developed in combination with novel genetic approaches to fate-map cells and selectively modulate androgen signalling. In vivo mouse models will be combined with tissue digest and cell isolation, transcriptomics analysis (including single cell RNA sequencing), multiparameter flow cytometry and immunohistochemistry.

These studies will determine how androgens regulate endometrial function in endometriosis and identify novel therapeutic targets that can be modulated to improve pregnancy health.  

PhD Pregnancy Research

This 3-and-a-half year PhD studentship programme aspires to train the next generation of scientists in tackling pain and distress during pregnancy, encompassing but not limited to the impacts of adverse pregnancy on the mother, fetus and subsequent generations, and how pregnancy is impacted by adverse maternal health. Students will receive cross-disciplinary training aimed at equipping graduates with skills to drive future developments in improving pregnancy outcome. 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.

The programme is based at the Centre for Reproductive Health (CRH) within the Institute for Regeneration and Repair (IRR).

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).

Applications from UK and non-UK based students are welcomed. The deadline for applications is June 6th 2024, and interviews will take place on June 26-28th 2024.

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.

Applicants are expected to have a good honours degree in the sciences (biological, chemical or physical), at least UK level of 2.1 or the equivalent from non-UK universities and meet the English language entry requirements. A Master’s degree in a relevant subject would be an advantage.

What is required:

• Personal statement (1 page in total) covering why you want to apply for a specific project(s). In the case you wish to be considered for more than 1 project, please indicate clearly your order of preference. 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 this template, 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.

All application documents should be emailed to [email protected] by the deadline for applications, 6 June 2024.  

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 the application. The interview lasting about 45 minutes, taking place on Microsoft TEAMS from June 26-28th 2024.