Spatiotemporal regulation of centriolar satellite homeostasis

Introduction

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.

Project Overview

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 signaling, and neurogenesis.

While CS functions have shed light on these organelles, little is known about their own biochemistry and how that affects their function.

Unique Properties of CS

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.

Hypothesis

Building on these discoveries, I hypothesize that CS perform their different functions by acting as adaptive organelles that remodel their granule features in response to intrinsic and extrinsic cues.

Research Objectives

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
3. CS heterogeneity within a cell and in different cell types

Methodology

This project will combine:

• In vitro reconstitution
• Imaging-based assays
• A new SatelliteGFP mouse
• Our expertise in proximity proteomics and biochemical purifications

Implications

Our results will have broad implications in unveiling how cells organize their cytoplasm in time and space appropriate to their differentiation status, environment, and organismal health.