Quantitative visualization of polarity protein complexes in Drosophila and mouse polarized epithelia (360G-Wellcome-109143_Z_15_A)

Epithelial cells have to establish and maintain apicobasal polarity to perform their vectorial secretory and absorptive functions. At the cellular level, polarity is defined by apical, lateral and basal domains, each marked by distinct polarity proteins localized at the cell cortex and in the cytoplasm. Based on biochemical and genetic evidence from C. elegans, D. melanogaster and cultured mammalian cells, these proteins are proposed to associate with each other and form spatially-restricted, mutually-antagonistic complexes. This model has proven difficult to test, since some proteins are thought to be involved in multiple complexes. An overarching goal for the field is to untangle the complicated model for polarity determination. I propose to contribute in the following two ways: firstly, to provide a direct evidence of polarity protein interactions and their stoichiometry within distinct complexes in Drosophila and mouse polarized epithelial cells using nanoscopy, and secondly, to investigate the molecular regulation of polarity orientation in intestinal organoids.