Neuro-immune regulation of Inflammatory bowel disease

PROJECT OVERVIEW

Intestinal tissue function, maintenance and repair depend on the integrated activity of multiple cell types. Disruption of this balance can result in chronic inflammatory conditions, such as inflammatory bowel disease (IBD). Numerous studies have uncovered important contributions of immune, epithelial and stromal cells in inflammatory responses and tissue repair of the intestine. However, treatment options for patients are still limited as the complex cellular interactions driving IBD pathogenesis and remission are highly variable, and only partly understood. The role of the nervous system and in particular neuro-/glial-immune interactions have emerged as important novel components of intestinal tissue maintenance, including their involvement in inflammatory responses and tissue repair.

This project aims to understand how the enteric nervous system regulates immune homeostasis and inflammation and to dissect the underlying pathways.

This project will first employ state-of-the-art single cell RNA sequencing and spatial transcriptomics analysis to uncover and comprehensively describe the functional role of the enteric nervous system in the context of intestinal inflammation and tissue remodelling. Taking findings further into in vitro organoid and in vivo mouse models, this project is uniquely capable of making fundamental and mechanistic insights into the contributions of neuro-immune interactions the pathogenesis of major intestinal inflammatory diseases that will likely advance the development of therapies. 

KEYWORDS

Mucosal immunology

Neuro-immunology

Inflammation

Gastrointestinal disease 

TRAINING OPPORTUNITIES

This interdisciplinary project synergises and integrates both wet lab experimental with computational approaches to uncover fundamental roles of the enteric nervous system in intestinal immunity in the context of inflammatory bowel disease. It is therefore suitable for a candidate that has a keen interest in cell biology and neuroimmune interactions and is passionate about discovering basic biological concepts. 

This project will provide high level training in cutting-edge genomic approaches, including the processing and analysis of single cell and spatial transcriptomic datasets. Mechanistic validation will be performed in human tissue culture systems or in vivo functional genomics and inflammatory models. 

Interested candidates are strongly encouraged to contact Dr Fränze Progatzky by email. 

KEY PUBLICATIONS

Progatzky, F., et al., Regulation of intestinal immunity and tissue repair by enteric glia. Nature, 2021. DOI:10.1038/s41586-021-04006-z 

Friedrich, M.; Pohin, M. et al., IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies. Nature Medicine, 2021. DOI: 10.1038/s41591-021-01520-5

Thomas, T. et al., A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease. Nature Immunology, 2024 DOI: 10.1038/s41590-024-01994-8

THEMES

Immunology

Molecular, Cell and Systems Biology

Translational Medicine and Medical Technology

CONTACT INFORMATION OF ALL SUPERVISORS

franze.progatzky@kennedy.ox.ac.uk