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Elucidating the interactions between the immune and the epithelial compartments in Inflammatory Bowel Disease using mini-guts.

Project details:

First supervisor: Dr Joana F Neves

Second supervisor: Dr Peter M Irving

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/01

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. 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 and lymphocytes in the context on intestinal associated diseases. We are particularly interested in exploring non-classical roles of Innate Lymphoid Cells, which we have recently identified (Jowett et al, under revision), in the promotion of intestinal epithelial cell regeneration and in the development of intestinal fibrosis.

Year 1: Use co-cultures of lymphocytes with intestinal organoids to identify potential pathways that govern the interaction between these cells (e.g. RNA-seq/scRNAseq).

Year 2: Validate the pathways identified (e.g. CRISPR/Cas9 technology).

Year 3: Modulate the new pathways using pharmacological approaches (drugs) using patient cells.

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 of techniques such as flow cytometry, imaging, molecular biology (including CRISPR), 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 by King's College London's Health Sciences Doctoral Training Centre. 

To view entry requirements and further general information, see Dental and Health Sciences Research MPhil/PhD prospectus page.

Next steps

Please apply online at following these steps:

  1. Register a new account/login
  2. Once logged in, select Create a new application
  3. 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
  4. Select 1 October 2020 as the start date
  5. Please note: Applicants must include the project reference number (2020/DOCS/01) 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. 

Contact for further information:

 Dr Joana F Neves


Related Centre:

Back to Research Projects main page.

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