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  Establishing patient-derived organoid reporter systems to facilitate precision medicine and personalised therapies for inflammatory bowel disease - Korcsmaros Group


   Department of Metabolism, Digestion & Reproduction

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  Dr Tamas Korcsmaros  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Inflammatory Bowel Disease (IBD) is a chronic, lifelong disease with significant morbidity, and its prevalence is forecasted to rise steeply in the decades ahead. Large-scale clinical cohort studies have associated changes of the gut microbiome (microbes and related metabolites) to the development of several digestive disease, including IBD. There is now a clear clinical need to uncover the consequences of altered microbial metabolite (e.g., bile acids) levels, and to design therapies based on the affected host processes.

This PhD proposal will aim to gain mechanistic insight into how the changed bile acid composition in the gut impacts epithelial homeostasis in IBD patients. This will uncover novel targets for improving the efficacy of IBD treatment.

To achieve this aim, the candidate will develop novel reporter-organoid lines from healthy and IBD patients by CrispR/Cas9 technology. This will allow them to monitor the inflammatory response and other intracellular processes, such as autophagy in the patients’ genetic background, which previously was not possible. Building on the Korcsmaros group’s previous results, which showed that the primary and secondary bile acids have different impact on the colonic epithelial cells, we aim to address the following questions:

1.      How does the bile acid composition affect the inflammatory response of the colonic epithelial cells in IBD patients?

2.      How do the bile acids modulate autophagy upon inflammation in the colonic epithelium of IBD patients?

3.      What alterations in the genetic background of the patients can explain the different responses of the epithelial cells?

This project will involve high level organoid culturing methods and modifications by CrispR/Cas9 technology. The developed organoid lines will be analysed by standard in vitro methods: Western blot, qPCR, ELISA, FACS, immunostaining and sequencing. Systems biology approaches will be applied for sequencing data analysis to understand the patient-specific responses to bile acids. The candidate will join the Imperial BRC Organoid Facility and will collaborate on data analysis with the Korcsmaros group.  Prior experience in gene engineering is desirable but not essential.  


Biological Sciences (4) Medicine (26)

Funding Notes

An opportunity has arisen for three 3-year PhD studentships, located within the Department of Metabolism, Digestion and Reproduction at Imperial College London, funded by the NIHR Imperial Biomedical Research Centre.
Funding: 36 months (full time), includes course fees at the UK-Home rate of £7,030.00 per year (Faculty of Medicine | Imperial students | Imperial College London) and a tax‐free stipend of £20,622. Funding for overseas fees is not provided. Descriptions of each project can be found below.
Starting date: 01 April 2024

References

All Imperial College London PhD entry requirements must be met and the successful applicant will subsequently need to apply online.
Applicants should hold (or obtain by January 2024) a first or upper-second-class honours degree. Applicants must also meet Imperial College’s English language requirements – further details can be found at https://www.imperial.ac.uk/study/pg/apply/requirements/english/.
We look forward to receiving applications from all candidates and will select those who display the potential to become world-leading researchers of the future based on their application and performance at an interview.
For queries about the application process please contact Alison Scoggins, (a.scoggins@imperial.ac.uk)
Applicants for this studentship should submit their CV and a cover letter, including full contact details of two referees, to Alison Scoggins (a.scoggins@imperial.ac.uk).
We regret that due to the large volume of applications received, we are only able to notify those shortlisted for interview.