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Nathan McDonald

Basic Life Science Research Associate, Biology

Current Research and Scholarly InterestsI am interested in the fundamental cell biology of neurons. In particular, I study how neuronal synapses are formed and function. Synapses are specialized intercellular junctions that facilitate rapid communication between neurons, and thus form the basis of neural circuits and nervous system function.

Within a synapse, synaptic vesicles containing neurotransmitters are released at a specific region termed the active zone. The active zone is composed of a variety of molecules that coordinate the tethering and priming of synaptic vesicles, the recruitment of ion channels to respond to action potentials, and the stabilization of the synapse through transmembrane connections to a postsynaptic cell.

A wide range of transmembrane proteins are capable of initiating synapse formation during development and provide specificity for targeting the proper postsynaptic cell, including Neurexins/Neuroligins, LRRTMs, DIPs/DPRs, and many Ig domain proteins. However, in all synapses, these molecules must signal to build a common active zone core. I am studying how the conserved active zone core assembles downstream of this complexity, a fundamental unresolved question in developmental neurobiology.

To study this problem, I use the simple and stereotyped nervous system of the nematode Caenorhabditis elegans. I use fluorescent imaging of endogenous proteins at single neuron and single synapse resolution, as well as genetic and biochemical methods.