About

We study the genetic pathways that enable neurons to reliably signal to other cells.  Much of neuronal signaling is the result of the controlled release of neurotransmitters, hormone-like molecules that act over very short distances and act on target cells such as other neurons or muscles. Abnormalities or dysfunction in this process can lead to neural disorders and disease. By resolving the molecular mechanisms that control the release of neurotransmitters in the model animal the roundworm Caenorhabitis elegans, we gain fundamental knowledge of how nervous systems work, and we gain practical knowledge that can lead to more effective drug therapies that target evolutionary conserved proteins between worms and humans.

C. elegans is a genetically tractable, optically translucent, fast breeding, easily cultivated animal used to study various aspect of biology. 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) is a regulator of fusion competency. The V-ATPase establishes the energy gradient needed for neurotransmitter loading of vesicles, but 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 analyze the structure and function of synapses by quantitative confocal imaging and patch clamp electrophysiology.