Mechanisms of epithelial polarity and polarised secretion

Epithelial cells—the sheets of cells that line organs and body surfaces—must sort thousands of different proteins to their top, bottom, and side surfaces to function correctly, but the molecular machinery that orchestrates this sorting remains largely unknown. This project addresses a fundamental gap in cell biology: how do cells know which proteins to send to which surface? When this sorting goes wrong, it contributes to diseases such as cystic fibrosis, kidney disorders, and cancer, where cells lose their organised structure. Understanding the basic mechanisms of protein trafficking is essential for grasping how these diseases develop. The researchers will use fruit fly egg chambers as a model system, releasing tagged proteins from the endoplasmic reticulum in synchronised bursts and tracking their journey to the correct membrane surface. They will identify the proteins that act as sorting factors by labelling molecules that share the same transport vesicles, then use genetic screens to test which polarity factors control these pathways. A separate line of work examines the fruit fly midgut, which polarises through a different mechanism and may better mirror how some human tissues organise themselves. This is fundamental science with no immediate practical application. However, similar curiosity-driven work on cell polarity and protein trafficking has previously underpinned advances in understanding how cancer cells lose their organisation and how genetic mutations disrupt organ function. A clearer picture of these sorting mechanisms could eventually inform strategies to restore normal cell architecture in disease.