About

We study the genetic pathways that enable neurons to reliably signal to other cells. Neural signaling depends on the controlled, activity-dependent release of neurotransmitters. These hormone-like molecules act over short distances and bind target cells such as other neurons or muscles. Abnormalities or dysfunction in this process can lead to neural disorders and disease.

We study neurotransmitter release in the model animal, the roundworm Caenorhabditis elegans. C. elegans is a genetically tractable, optically translucent, fast-breeding, easily cultivated animal used to study various aspects of biology. Using this model system, we gain fundamental knowledge of how animal nervous systems work and practical knowledge that can lead to more effective drug therapies targeting evolutionary conserved proteins between worms and humans.

We are focused on resolving how neurotransmitters are packaged into synaptic vesicles and how the release of loaded synaptic vesicles is regulated. We are testing the hypothesis that the synaptic vesicle proton pump (V-ATPase) regulates fusion competency. The V-ATPase establishes the energy gradient needed for neurotransmitter loading of vesicles. Still, findings by our lab and others indicate the V-ATPase may have other roles besides its well-defined role in loading. At what step in the synaptic vesicle does the V-ATPase act? To address this question, we analyze the effects of the V-ATPase mutations on locomotion behavior and sensitivity to drugs that interact with proteins in the neurotransmitter release and synaptic vesicle recycling pathway. Using fluorescence reporters and optogenetic stimulation, we, with a network of collaborators, analyze the structure and function of synapses using quantitative confocal imaging, patch clamp electrophysiology, and electron microscopy.