Nathan McDonald

My lab investigates how our brains and nervous systems develop and function. We aim to understand molecularly how neurons build synapses, the specialized junctions that support rapid neuronal communication. Our brains build ~100 trillion synapses during development and continue to build synapses in daily adult life. The location and properties of these synaptic connections fundamentally determine neuronal function. We aim to understand how synapses are formed and function at a molecular and cellular level to advance a bottom-up understanding of the brain and identify avenues for the regeneration of synapses in neurodegenerative diseases. We approach this question using live-animal super-resolution imaging of synapse formation, in vitro biochemical reconstitutions, and genetics with CRISPR/Cas9. We primarily use the model organism C. elegans, a nematode worm with a well-defined nervous system containing just 302 neurons that make around 7000 synapses. With these tools, we are currently investigating synaptic cell adhesion signaling pathways and the liquid-liquid phase separation of core synaptic proteins as conserved mechanisms of synapse formation.