Studying immune-epithelial-microbial interactions in Inflammatory Bowel Disease using mini-guts
Project details
First supervisor: Dr Joana F Neves
Second supervisor: Professor Michael Curtis
Sponsor: (joint) Guy's and St Thomas' Biomedical Research Centre and King's College London Faculty of Dentistry, Oral & Craniofacial Sciences
Funding available: MRC rate stipend & £5k per annum bench fee
Duration of award: 3 years
Mode of study: Full time
Eligibility: Home/EU
Start date: 1 October 2020
Application deadline: 14 February 2020
Reference number: 2020/DOCS/02
Project description
The maintenance of intestinal homeostasis depends on the interactions between several compartments including the gut epithelium, the intestinal microbiota and the gut-associated immune system. Disrupting this delicate balance results in intestinal inflammation, which is associated with several diseases such as Inflammatory Bowel Disease (IBD), cancer and neurodegenerative diseases.
We developed a novel system of lymphocyte cultures in intestinal organoids (“mini-guts”) that mimics the intestinal environment. Intestinal organoids are generated from intestinal stem cells that differentiated into the several types of intestinal epithelial cells forming intestinal crypts. We can add bacteria and bacterial metabolites to our innovative culture system to determine how these microbial components influence immune and epithelial cell phenotype and function (Figure-1). This is disease relevant as IBD patients present altered metabolite composition in their gut due to due to differences in composition of their microbiota.
This pioneer system led us to identify novel roles for innate lymphoid cells (ILC) (Jowett et al, under revision) in regulating intestinal epithelial cells and fibroblast proliferation and function. To facilitate the translation of our discoveries our co-culture system is established with human cells allowing us to use patients’ cells to test the importance of our novel pathways in the clinical setting and the potential to modulate these pathways to promote health.
The overall aim of this project is to identify key pathways responsible for the crosstalk between intestinal epithelial cells, lymphocytes and bacteria in the context on intestinal associated diseases. IBD patients have alterations in the composition of their gut microbiota, with less diversity and accumulation of pathogenic strains. However, the cellular and molecular mechanisms associated with such changes are still being elucidate and using our novel reductionist system we aim to pinpoint the effect of specific bacteria on the epithelial and immune compartments.
During this project the student will acquire a wide range techniques such as flow cytometry, imaging, molecular biology (including CRISPR), microbiology, transcriptomics, single cell RNAseq, epithelial, lymphocyte and stem cell biology and mucosal immunology techniques.
Person specification
Candidates must possess, or be expected to achieve a 1st or upper 2nd class degree in a relevant subject including the biosciences, chemistry, physics, computer science or mathematics, and be enthusiastic about combining their expertise with other disciplines in the field of healthcare. The full fellowship is open to EU/Home students only
Research training
During this project the student will acquire a wide range techniques such as flow cytometry, imaging, molecular biology (including CRISPR), microbiology, transcriptomics, single cell RNAseq, epithelial, lymphocyte and stem cell biology and mucosal immunology techniques.
Students will also have access to a wide range of short courses provided through the KCL Health Sciences Doctoral Training Centre (https://www.kcl.ac.uk/study/doctoral-studies/health-sciences-doctoral-training-centre/workshop-and-course-listings)
To view entry requirements and further general information, see Dental and Health Sciences Research MPhil/PhD prospectus page.
Next steps
Please apply online at apply.kcl.ac.uk following these steps:
- Register a new account/login
- Once logged in, select Create a new application
- Enter ‘Dental and Health Sciences Research MPhil/PhD (Full-time)/(Part-time)' under Choose a programme. Please ensure you select the correct mode of study
- Select 1 October 2020 as the start date
- Please note: Applicants must include the project reference number (2020/DOCS/02) in the 'Research proposal' and 'Funding (point 5)' sections of the application.
Applications must be received by the deadline specified in this listing.
Applicants are strongly encouraged to discuss projects with the first supervisor prior to submitting an application.
Dr Joana F Neves
Email: joana.pereira_das_neves@kcl.ac.uk
Related Centre: https://www.kcl.ac.uk/dentistry/research/centre-for-host-microbiome-interactions
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