Our lab is interested in understanding how neural circuits are formed, dismantled, or modulated to properly regulate behavior. We use genetics, cell biology and biochemistry to elucidate how neuronal and non-neuronal/glial mechanisms regulate neural circuit function.
Small GTPase Regulation of synapse development.
Synapse development is a highly orchestrated process that requires the coordination of cell adhesion signaling, cytoskeletal dynamics, and intracellular trafficking. We recently that PXF-1, a Rap guanine nucleotide exchange factor, promotes presynaptic actin filaments, synapse development, and neuromuscular function (Lamb et al. 2022). We are currently focusing on identifying the signaling pathways that enable PXF-1 to coordinate the development and function of presynaptic terminals in cholinergic motor neurons.
Non-neuronal regulation of synaptic connectivity.
In C. elegans, neuromuscular junctions (motor neuron connections with muscle) are also physically contacted and modulated by the epidermis. This provides a unique system to investigate how non-neuronal cells, similar to glia, regulate synaptic function and behavior. Using this approach, we have begun to uncover signaling mechanisms that regulate synapse elimination (Cherra and Jin, 2016; Cherra et al. 2020). We are currently dissecting how phagocytosis in the epidermis is used to remove synapses between motor neurons and muscle.
Regulation of neural circuit function by novel synaptic proteins.
Synaptic function is regulated at many levels, including synaptic vesicle trafficking, neurotransmitter loading, and vesicle docking and exocytosis. We are currently investigating how newly identified synaptic proteins and novel mutations in synaptic proteins regulate synaptic transmission and neural circuit function (McCulloch et al. 2017).