About the Project
In this project, we will utilise mucosal immunology expertise within the Lydia Becker Institute combined with endometrial organoid culture, which the Maternal and Fetal Health Research Group are extensively specialised in. This project will dissect immune cell interactions in models of proliferative, receptive and decidual endometrium for the first time, to enable characterisation of critical regulators of implantation in early pregnancy. The establishment of complex endometrial organoids will also enable investigation of interventions for endometrial pathologies. Intrauterine treatment with placental hormone human chorionic gonadotropin (hCG) at the time of embryo transfer is an intervention in assisted reproductive technologies (ART) that has been shown to greatly improve live birth rates, likely through local action on the receptive endometrium. Assaying the effects of hCG in complex organoids will provide mechanistic insight into emerging treatment.
Training/techniques to be provided:
Whole organ phyioslogy – development of multi cell-type 3D cultures from primary tissue to recapitulate in vitro endometrial function using organoid culture system.
Mucosal immunology techniques – processing human mucosal tissue for cellular and molecular characterization of endometrial immune cells (flow cytometry and molecular techniques).
Bioinformatics: characterisation of immune cells using techniques such as single cell RNAseq
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a topic related to biological and medical sciences. Candidates with experience in cell biology, development or immunology or with an interest in reproductive medicine are encouraged to apply.
For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
Scott, N.A., Andrusaite, A., Andersen, P., Lawson, M., Alcon-Giner, C., Leclaire, C., Caim, S., Le Gall, G, Shaw, T., Connolly, J.P.R., Roe, A.J., Wessel, H., Bravo-Blas, A., Thomson, C., Kästele, V., Wang, P., Peterson, D.A., Bancroft, A., Li, X., Grencis, R., Mowat, A.M., Hall, L.J., Travis, M.A., Milling, S.W.F. and Mann, E.R. (2018). Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis. Science Translational Medicine. 10(464)
Kelly, A., Gunalty, S., McEntee, C.P., Shuttleworth, E.E., Smedley, C., Houston, S.A., Fenton, T.M., Levison, S., Mann, E.R. and Travis, M.A. (2018). Human monocytes and macrophages regulate immune tolerance by integrin avb8-mediated TGFb activation. Journal of Experimental Medicine. 215(11):2725-273
PT Ruane, C Buck, PA Babbington, W Aboussahoud, SC Berneau, M Westwood, SJ Kimber, JD Aplin, D R Brison (2019). The effects of hyaluronate-containing medium on human embryo attachment to endometrial epithelial cells in vitro. Human Reproduction Open. In Press
PT Ruane, SC Berneau, R Koeck, J Watts, SJ Kimber, DR Brison, M Westwood, JD Aplin (2017). Apposition to endometrial epithelial cells activates mouse blastocysts for implantation. Molecular Human Reproduction 23:617-627.
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