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EASTBIO: The role of peritoneal macrophages in fetal/maternal health during pregnancy


College of Medicine and Veterinary Medicine

Dr Stephen Jenkins , Wednesday, January 06, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

Sex is a major variable effecting inflammation and immunity. The mechanisms controlling sex dimorphisms are thought to have evolved from the need for the maternal immune system to allow development of immunologically ‘foreign’ off-spring while maintaining integrity of immune barriers during gestation and providing maternal transfer of immunity to neonates. However, while the process of adaptive immune tolerance during pregnancy is well established, how maternal resistance to infection is maintained during gestation and why this sometimes fail remains unclear. Understanding this is critical for the health and well-being of mothers and neonates, since at least 40% of pre-term births are attributable to intrauterine infection in mothers, and maternal reproductive tract infections still account for approximately 10% of deaths in women around the time of pregnancy.

We recently identified that resident macrophages in the peritoneal cavity of female mice are primed to provide heightened resistance to peritoneal infection (1). We still do not know why these cells exhibit this heightened barrier function. Revealingly, peritoneal macrophages are also implicated in sexually-dimorphic production of natural antibody that protect females and developing offspring against enteropathogenic infection (PMID: 30250184), but also have a unique migratory capacity allowing them to rapidly enter injured internal organs to promote tissue repair and prevent fibrosis (2).
In this project, the student will test the hypothesis that in females, peritoneal macrophages are geared to resist and deal with ascendant intrauterine bacterial infection during pregnancy and/or uterine remodelling that occurs during pregnancy and post-birth. Using our novel physiologic model of ascending intrauterine infection with Ureaplasma parvum that leads to pre-term birth in mice (3) combined with in vivo cell fate-mapping and cell-depletion strategies, the student will determine how peritoneal macrophages respond and function during pregnancy and pre-term infection in mice.

The student will use techniques including whole mount imaging, immunofluorescence microscopy and multi-colour and spectral flow-cytometry of uterine fluid and tissue digests to fate map and interrogate peritoneal macrophages deep within reproductive tract tissue. They will be fully trained in all these techniques as well as in statistics, presentation skills, writing skills, and data management.


Application Process:

For instructions on how to apply for an EASTBIO PhD studentship please refer to http://www.eastscotbiodtp.ac.uk/how-apply-0

Contact Dr Steve Jenkins before you apply.

We anticipate all EASTBIO (online) interviews will be in the week 8-12 February 2021 with awards made the following week.

Please submit all required documents directly to

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.




Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is open to UK and international students and provides funding to cover stipend and UK level tuition fees. The UoE covers the difference between home and international fees. There is a cap on the number of international students the DTP can recruit so it is important to know in which fees status category applicants fall under when formally applying.

Refer to UKRI website View Website and Annex B of the UKRI Training Grant Terms and Conditions View Website for full eligibility criteria.

References

1 Bain, C. C. et al. Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages. Sci Immunol 5, doi:10.1126/sciimmunol.abc4466 (2020).
2 Wang, J. & Kubes, P. A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair. Cell 165, 668-678, doi:10.1016/j.cell.2016.03.009 (2016).
3 Pavlidis, I. et al. Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice. Nat Commun 11, 199, doi:10.1038/s41467-019-14089-y (2020).


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