Goblet cell intrinsic determinanats of intestinal mucus function in health and disease

Non-communicable intestinal mucosal diseases affect millions of people and are expected to rise in prevalence due to the impacts of modern lifestyle changes.

Common to these diseases are alterations in the mucus layer protecting the mucosal epithelium, demonstrating the critical importance of proper mucus function in the maintenance of health and prevention of disease.

However, the biochemical and cellular properties that allow formation of a healthy mucus layer, and how these are disturbed in disease, remain largely undefined.I have previously identified heterogeneity in intestinal mucus producing goblet cells and in the mucus that they produce.

By combining single-cell RNA sequencing, unique ex vivo mucus characterization, intersectional genetic approaches for cell-subtype specific metabolic labelling of proteins, and mass-spectrometry based analysis of post-translational modifications, I aim to determine the biochemical link between different subtypes of goblet cells and mucus function.

This will be done both in mouse and human to provide a translational roadmap, and in murine challenge models to investigate the role of goblet cell compositional alterations in disease.

The proposed research will provide unprecedented detail regarding the role of goblet cells and mucus in intestinal physiology and will lay a foundation for future research to develop strategies to prevent or cure non-communicable mucosal disease.