CILIAMIC

Cilia are microtubule-based structures present on the surface of most vertebrate cells, playing crucial sensory and motile roles. Dysfunction in cilia leads to severe disorders known as ciliopathies, which affect vital organs in multiple ways, notably the kidneys, heart, and brain. Studying cilia biogenesis and homeostasis is critical to understanding the origins of these diseases. Cilium formation is mediated by microtubule elongation from the centriole, a process intimately linked to membrane remodeling. Throughout the life of a cilium, its membrane undergoes significant morphological modifications and reorganization of protein distribution. Despite advances in understanding ciliary structure and function, the molecular mechanisms controlling membrane dynamics during the cilia life cycle remain poorly understood, largely due to challenges in visualizing these dynamics. Cilia are minute organelles that require high-resolution techniques like electron microscopy; however, observing membrane dynamics requires live or dynamic optical microscopy, which often lacks the necessary resolution for such small structures. This research project aims to identify the molecular players and key steps involved in membrane remodeling during the life cycle of mammalian cilia. The project will be carried out through two specific aims: 1) Characterize the membrane composition and organization supporting cilia dynamics using a combination of live membrane labeling and advanced super-resolution microscopy. 2) Dissect the molecular functions of canonical membrane remodeling proteins in cilia homeostasis and ciliopathy-related brain disorders using advanced super-resolution microscopy and genetic manipulation. Overall, this project seeks to uncover the molecular mechanisms of ciliary membrane remodeling, potentially revealing new pathways that contribute to ciliopathies.