Elucidating the impact of adherent-invasive E. coli on the microbiome and gut epithelium in Crohn’s disease (SCHULLER_U23MMB)

Crohn’s Disease (CD) is a chronic inflammatory bowel disorder affecting > 120,000 people in the UK. It is often diagnosed in young adulthood, and symptoms include chronic abdominal pain, diarrhoea, and weight loss. Current therapies are aimed at reducing inflammation but come with severe side effects. There is no cure, and many patients require surgery. The specific causes for CD remain unknown, but research suggests that environmental and/or genetic factors lead to microbial dysbiosis resulting in a leaky gut epithelium and overactive immune response. Notably, a particular type of adherent-invasive E. coli (AIEC) is highly prevalent in CD tissue, but it remains unclear if AIEC is a cause or consequence of CD. In this project, we will determine the role of AIEC in CD by elucidating its interaction with the microbiome and the gut epithelium. We will achieve this by 1) investigating the influence of AIEC on the microbiome (and vice versa) in an artificial colon model, 2) establishing human intestinal organoids from tissue of CD patients and healthy controls and characterising their barrier function and inflammatory response, and 3) deciphering AIEC-microbiome-organoid crosstalk in a novel anaerobic cell-microbe co-culture system. Results from this project will contribute to the development of better therapies for CD aimed at restoring microbe-epithelial homeostasis.

The project will be suited for a motivated student with a strong interest in microbiology, cell biology and bioinformatics. You will join an interdisciplinary and supportive research environment at the UEA (Stephanie Schuller), the Quadram Institute Bioscience (Arjan Narbad), and the Earlham Institute (Christopher Quince). Expert training in anaerobic bacterial culture, molecular biology, human organoid culture and confocal microscopy will be provided. In addition, you will acquire advanced skills in metagenomic data analysis and operation of the human colon model and anaerobic cell-microbe vertical diffusion chamber.

The Microbes, Microbiomes and Bioinformatics (MMB) Doctoral Training Partnership (DTP) is open to UK and international candidates with relevant undergraduate degrees for entry in October 2023 and offers the opportunity to undertake a 4-year PhD research project funded by the UKRI Medical Research Council in microbiology and microbial bioinformatics.

Our unique and comprehensive training programme empowers students to feel comfortable running sophisticated computer analyses alongside laboratory work and emphasises problem-based learning in microbial bioinformatics, professional development and research skills. All students will undertake a Professional Placement.

Interviews for shortlisted candidates will take place on Wednesday 15 February or Tuesday 16 February 2023.

The MRC DTP is committed to equality, diversity and inclusion. Students are selected without regard to age, disability, gender identity, marriage or civil partnership, pregnancy or maternity, ethnicity, religion or belief, sex or sexual orientation or social background. We value curiosity, independence of thought, plus an aptitude for research that combines laboratory work and bioinformatics.