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EASTBIO: Defining the impact of androgens on macrophage function in women’s reproductive health


   College of Medicine and Veterinary Medicine

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  Dr D Gibson, Prof I McEwan  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

One in three women in the UK will suffer from a reproductive health problem such as polycystic ovarian syndrome, heavy menstrual bleeding or endometriosis. These common disorders cause debilitating, life-changing symptoms and are associated with dysregulated function of the womb lining (endometrium). We need to understand the factors that cause disrupted function of the endometrium and the cell types that are affected in order to develop new therapies for gynaecological disorders.

Androgens are essential mediators of reproduction but their role in regulating the endometrium is poorly understood. We have profiled patients with reproductive disorders and found that their hormone profile is altered and they exhibit increased concentrations of androgens in their blood. In experimental models, we found that excess androgens could disrupt endometrial function by delaying endometrial repair following menses. This was associated with decreased expression of tissue remodelling factors and markers of cell apoptosis. Endometrial repair requires coordinated changes in specialised immune cells called macrophages that regulate tissue remodelling and repair. Macrophages are therefore important mediators of tissue repair and, importantly, their function is known to be dysregulated in reproductive health disorders. It is not known if their function can be directly or indirectly altered by androgens in the endometrium.

This project will determine how androgens alter macrophage function in the endometrium by performing phenotypic and transcriptomic characterisation of macrophages using cell and mouse models. The impact of androgens will be assessed by using genetic and pharmacologic manipulation of androgen signalling to uncover androgen-dependent pathways that regulate macrophages in the endometrium. These studies will define how androgens affect turnover and maintenance of macrophages in the endometrium and how this can affect macrophage phenotype and function. Collectively, these studies will provide unique insights into how changes in androgens can affect macrophage function and alter reproductive health outcomes.

Funding information and Application Process:

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP)

This opportunity is open to UK and international students and provides funding to cover stipend and UK level tuition fees. The University of Edinburgh will cover the difference between home and international fees meaning that the EASTBIO DTP will offer fully-funded studentships to all appointees. However there is a cap on the number of international students the DTP can recruit. It is therefore important for us to know from the outset which fees status category applicants will fall under when formally applying for entry to our university.

Please refer to UKRI Website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.

Informal enquiries should be addressed to Dr Gibson. To apply, please send a cover letter outlining your previous research experience and reasons for applying, alongside an up-to-date CV to [Email Address Removed]

Download and complete our Equality, Diversity and Inclusion survey and then fill in the EASTBIO Application Form and submit it, along with a copy of your academic transcripts, to [Email Address Removed] before the application deadline.

You should also ensure that two references have been sent to [Email Address Removed] by the deadline using the EASTBIO Reference Form

We anticipate that our first set of interviews will be held 6th – 10th February 2023 with awards made in the following week.

If you have further queries about the application/recruitment process please contact [Email Address Removed]

The research group is located in the University of Edinburgh Centre for Inflammation Research; a world-class research environment at the interface between biological and medical science, with multidisciplinary groupings focused on inflammation, infection, disease and repair. The Centre is based within the Edinburgh Medical School in the outstanding facilities of the Queen’s Medical Research Institute at the site of the Royal Infirmary of Edinburgh hospital, maximising future translational opportunities


References

1. Hunter et al (2018) Tissue control of androgen action: The ups and downs of androgen receptor expression. Mol Cell Endocrinol. 465: 27-35.
2. Cousins, F.L., et al., Androgens regulate scarless repair of the endometrial “wound” in a mouse model of menstruation. The FASEB Journal, 2016. 30(8): p. 2802-2811.
3. Cousins, F.L., et al., Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling. Scientific Reports, 2016. 6(1): p. 36748.

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