Background
Barrier tissues such as the gut and lung form dynamic interfaces with the external environment, balancing immune defence with tolerance to commensal microbes and environmental exposures. While epithelial cells have traditionally been viewed as passive structural barriers, emerging evidence suggests they actively instruct local immune responses and contribute to immune homeostasis.
Major histocompatibility complex class II (MHCII) enables the presentation of processed peptide antigens to CD4⁺ T cells, orchestrating antigen-specific adaptive immunity. Although this function is classically attributed to professional antigen-presenting cells (APCs), epithelial MHCII expression has been observed in mucosal tissues and is upregulated in chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, the molecular mechanisms regulating epithelial antigen presentation and its functional consequences remain poorly understood.
Aim
This project will define how epithelial cells regulate antigen presentation and directly shape adaptive immune responses in barrier tissues by:
- Defining the inflammatory and microbial signals that regulate epithelial MHCII expression
- Identifying molecular pathways controlling epithelial antigen-presentation machinery
- Determining how epithelial antigen presentation influences CD4⁺ T cell activation.
Approach
Candidates are expected to have a strong foundation in laboratory-based research and a genuine interest in immunology and/or intestinal biology. The student will employ sophisticated epithelial culture systems, including mammalian cell lines and patient derived intestinal organoids (3D mini-gut cultures), alongside organoid-immune cell co-culture models to perform perturbation and functional assays. These experiments will be complemented by immunophenotyping approaches, including flow cytometry and immunofluorescence microscopy, together with bulk, single-cell, and spatial transcriptomic profiling. There will also be opportunities within the lab to gain experience in bioinformatic analysis of high-dimensional transcriptomic datasets, enabling integration of experimental and computational approaches.
Project Potential
This project addresses a fundamental question in mucosal immunology: do epithelial cells instruct adaptive immune responses at barrier surfaces? By combining mechanistic experiments with patient derived organoid-immune co-culture systems, this work aims to define epithelial-specific pathways that regulate immune activation and tolerance.
Outcomes from this research have strong translational relevance for diseases characterised by barrier dysfunction and chronic inflammation, including inflammatory bowel disease. The project forms part of a broader Barrier Immunity research program integrating experimental and computational approaches, with strong potential for high-impact publications and future therapeutic discovery.
