Modelling scar formation in endometriosis

Description

This opportunity will remain open until the position has been filled and so early applications are encouraged.

Endometriosis affects 10-15% of women during their reproductive years and is often associated with debilitating pelvic pain and impaired fertility. It is a chronic inflammatory condition characterised by the presence of endometrium-like tissue at ectopic sites, called endometriotic-lesions. Endometriosis is primarily caused by retrograde menstruation, and is influenced by the hormones of the menstrual cycle. Peritoneal scarring and the formation of adhesions (fibrous bands) between organs and tissues are commonly associated with endometriosis. Although similar inflammatory changes occur in the correctly located uterine endometrium, unlike with endometriotic lesions, there is no associated fibrosis formation, suggesting that fibrosis is caused by an aberrant immune response. The endometriosis-associated fibrotic scars and adhesions complicate any treatment since surgical removal of the affected tissue can involve also the reproductive organs, leading to infertility, while surgery itself can cause further scarring.

Our overarching aim is to develop preventative treatments for endometriosis-associated scar and adhesion formation in order to reduce the negative impact of endometriosis on the physical and mental wellbeing of the patients.

Endometrium-like cells and immune cells in endometriotic lesions have been well studied with targeted treatments, but the process of peritoneal scarring is not well understood. To address this unmet clinical need and develop successful therapies, we require in-depth knowledge of the cellular and molecular contribution to endometriotic lesions and associated fibrosis. A multi-cellular in vitro model that reflects the processes involved will allow detailed analyses and testing of therapeutic interventions. It is important to note that preclinical small animal models are not suitable because the essential biological requirement for endometriosis-formation, menstrual endometrial shedding, is unique to humans.

In this project, we will generate a patient-derived multi-cellular 3D model of endometriosis and peritoneal fibrosis. This will involve the establishment and optimisation of advanced human peritoneal wall-culture systems from isolated mesothelial cells and peritoneal fibroblasts. As a next step, we will combine previously established endometrial organoids with the peritoneal wall-cultures and inflammatory cells to mimic the conditions associated with endometriosis and peritoneal scar formation.

Although 3D models of endometriosis have been developed, the aspect of peritoneal scarring is currently lacking. By establishing this model, we will provide the necessary platform to perform targeted analysis of the pathophysiological conditions that lead to endometrial scarring, which can be exploited for the development of therapies and personalised medicine studies.

This studentship will utilise state-of-the-art technology and world-leading equipment and facilities, bringing together a unique opportunity for a student to analyse fundamental mechanisms of early embryonic development that are relevant for tissue regeneration processes in vascular smooth muscle cells of the cardiovascular system.

The successful student will gain training in a multitude of techniques, including primary human cell and organoid culture, establishing a 3D peritoneal wall model, immunofluorescence staining, flow cytometry and protein expression analysis (Western etc), confocal and lightsheet microscopy, image analysis and introduction to biostatistical approaches and data handling including R.

The research project will be based in the Department of Molecular Physiology and Cell Signalling at the University of Liverpool.

For any enquiries please contact Dr Bettina Wilm, 

Application is by CV and covering letter.  The covering letter must detail your interest in the studentship, related experience and training and suitability for the position.  Applications should be sent to Dr Bettina Wilm, 

Availability

Open to students worldwide

Funding information

Self-funded project

We are looking for a self-funded student or a student who have secured funding from an independent body. There is no financial support available from Liverpool for this study. Please see website for PhD student fees at the University of Liverpool: View Website.

The successful applicant will be expected to have funding in place for the tuition fees (check University of Liverpool website), consumables/bench fee (£ 18,000 per annum) and living expenses during their stay in Liverpool.

New self-funded applicants may be eligible for a tuition fees bursary (UK applicants only) or a £2000 ISMIB Travel and Training Support Grant.

Supervisors

References

1. Wilm et al. (2005) The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development 132(23):5317-5328. Doi: 10.1242/dev.02141
2. Held et al. (2018) Ex vivo live cell tracking in kidney organoids using light sheet fluorescence microscopy. PLoS One 26;13(7):e0199918. doi: 10.1371/journal.pone.0199918.
3. Dauleh S, Santeramo I, Fielding C, Ward K, Herrmann A, Murray P, Wilm B. (2016) Characterisation of cultured mesothelial cells derived from the murine adult omentum. PLoS One. 11(7):e0158997. DOI: 10.1371/journal.pone.0158997.
4. Kawaguchi M, Bader DM, Wilm B. (2007) Serosal mesothelium retains vasculogenic potential. Dev. Dyn. 6(11):2973-9