University College London Featured PhD Programmes
University College London Featured PhD Programmes
Ulster University Featured PhD Programmes
Ulster University Featured PhD Programmes
Loughborough University Featured PhD Programmes

Studying immune-epithelial-microbial interactions in Inflammatory Bowel Disease using mini-guts

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.

Funding Notes

• Sponsor: BRC / KCL FoDOCS

• Stipend and/or bench fees (amount): MRC rate stipend & £5k per annum bench fee

• Tuition fees (Y)

• Duration of award/project: 3 years

• Eligibility: Home/EU

• Mode of study: Full time

How good is research at King’s College London in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 52.95

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully

FindAPhD. Copyright 2005-2020
All rights reserved.