Mechanobiology of intestinal goblet cells – GOBLET

The gut epithelium is single layer of cells and a physical barrier towards the harsh luminal environment. It is also the fastest renewing tissue in the body – the turnover is maintained by cell proliferation in the crypts, migration of differentiated cells along the villi, and cell loss by extrusion. In addition to these intrinsic dynamics, the tissue is constantly mechanically challenged by extrinsic factors, such as muscle contractions.
Epithelial cell junctions enable tissue cohesion and collective cell migration – they mechanically link cells, integrating forces across the tissue, and modulating cell behaviour. However, the small intestinal epithelium comprises six different cell types with distinct roles, morphologies and turnover rates. The predominant cell type – enterocytes (absorptive cells) – are columnar with polygonal apical shape, and were shown to turnover fast. The other, rarer cell types, have round apical shapes and secretory roles, and many were shown to renew more slowly than enterocytes.
How cell-cell junctions are maintained in a tissue with a diversity of cell types with such distinct morphology and turnover rates is unknown.
Here we focus on goblet cells, which have an extremely bulky, round-shaped body, due to mucus granules.
Main aims of GOBLET are to understand the impact of goblet cells on epithelial integrity, and to reveal goblet cell dynamics in gut homeostasis.
To this end we propose an interdisciplinary and collaborative project, using complementary model systems such as transgenic mice, ex vivo tissue and organoid models, combined with advanced imaging systems and biophysical modelling, to understand the impact of cell heterogeneity in the gut homeostasis.