Mechanisms of epithelial polarity and polarised secretion

Epithelial cells localise specific proteins their apical, lateral and basal sides to perform different functions in each domain, but how apical-basal polarity factors control this is unknown.

We will investigate exocytic trafficking in Drosophila follicle cells by inducing the synchronous release of apical, lateral and basal cargoes from the endoplasmic reticulum and imaging their trafficking to the plasma membrane.

We will identify sorting/targeting factors by proximity-labelling proteins in the same vesicles as our cargoes and perform functional screens using RNAi and acute knockdown to determine how polarity factors control these trafficking pathways.

We will also analyse how polarity proteins regulate the apical-basal microtubule arrays along which exocytic vesicles are transported.

We discovered that the midgut polarises by a different mechanism from other Drosophila epithelia and may provide a better model for some mammalian epithelia.

We will identify epithelial polarity factors in the midgut in clonal screens, characterise their functions and test whether they play conserved roles in mammals by knocking down their orthologues in organoids.

This research will reveal the mechanisms that polarise different epithelial types and target membrane proteins to the right place, which is essential for understanding epithelial function and how it is perturbed in disease.