| Project Detail |
Membrane-less compartmentalization has emerged as a powerful, yet mysterious, process for the spatiotemporal control of fundamental cellular processes. How the identity of a membrane-less organelle is established, maintained, and dynamically altered remains unclear. In this project, I will investigate the fascinating biology of the centriolar satellites (hereafter CS), a vertebrate-specific membrane-less organelle. CS was first discovered as granules that cluster and move around centrosomes – major microtubule-organizing centers of animal cells. Recently, my lab and others have placed CS in a new pathway for targeting proteins to centrosomes and cilia, and identified an important role for CS in cell division, cellular signalling and neurogenesis. While CS functions shone light in these organelles, little is known about their own biochemistry and how that affects their function.
Recent studies, including my own, revealed unique and intriguing CS properties that likely underlie the rules underpinning their regulation and function. The properties of CS granules are regulated in space, time and tissue, as we observe differential size and composition within the cell and in different cell types. Building on these discoveries, I hypothesise that CS perform its different functions by acting as adaptive organelles that remodel its granule features in response to intrinsic and extrinsic cues. With this project I propose to investigate the molecular basis of (1) CS scaffold assembly and disassembly, (2) CS granule size, composition, architecture and dynamics; and (3) CS heterogeneity within a cell and in different cell types. This project will combine in vitro reconstitution, imaging-based assays, a new SatelliteGFP mouse and our expertise in proximity proteomics and biochemical purifications. Our results will have broad implications in unveiling how cells organize its cytoplasm in time and space appropriate to its differentiation status, environment and organismal health. |
