Semi-ordered Macromolecular Assemblies in Neuronal Organisation and Function

Neuronal function depends on the precise spatial and temporal organisation of RNA, proteins, and extracellular cues that coordinate cellular architecture and circuit activity. Two key regulators of these processes are ribonucleoprotein (RNP) granules and the extracellular matrix (ECM). RNP granules are dynamic biomolecular condensates that organise RNA and proteins to control translation, neuronal polarity, and synaptic signalling, whereas ECM components provide structural and biochemical cues that guide neuronal morphology, connectivity, and receptor localisation. Using Caenorhabditis elegans, I investigated the conserved ubiquitin-associated protein PLAA/UFD-3 and discovered that it regulates proteome homeostasis through two distinct mechanisms: ubiquitin-dependent protein turnover and intrinsically disordered region (IDR)-mediated control of RNP granules. In parallel, I identified specialised extracellular matrix assemblies at the interface between epidermal cells and touch receptor neurons that organise mechanotransduction channels required for vibrotactile sensation, demonstrating how neurons repurpose conserved basal lamina proteins to construct specialised sensory structures. Building on these discoveries, my future research program will investigate how membraneless RNA-protein condensates and extracellular matrix architecture cooperate to regulate neuronal polarity, circuit assembly, and plasticity. By integrating genetic, proteomic, imaging, and behavioural approaches, my work aims to uncover fundamental principles linking biomolecular condensates and extracellular signalling to neuronal organisation and neurological disease.