Dept.: Assistant Professor, Department of Biochemistry
Neuroscience Focus Groups: Cell and Molecular Neuroscience, Invertebrate Neurobiology, Neurotransmitters, Modulators, Transporters and Receptors
We are interested in the function of neuromodulators. The nervous system uses two modes of chemical signaling at synapses. Fast signaling occurs by the release of small molecule neurotransmitters that activate ligand-gated ion channels. Slower signaling occurs by the release of neuromodulators that activate seven-transmembrane receptors coupled to heterotrimeric G proteins. Neuromodulators are typically neuropeptides, or monoamines such as dopamine, noradrenaline, and serotonin. Defects in neuromodulatory pathways do not usually lead to death, but can cause mental disorders such as depression, schizophrenia, autism, and attention deficit and hyperactivity disorder, as well as eating disorders and drug addiction. Neuromodulators are released from dense-core vesicles. Thus, a molecular understanding of neuromodulation requires both an understanding of the regulation of dense-core vesicle release as well as the G protein signal transduction pathways that respond to neuromodulatory signals.
We use molecular biology, genetics, biochemistry and novel imaging techniques in C. elegans to understand how neuromodulators are packaged into dense-core vesicles, how these vesicles are trafficked and released, and how cells respond to neuromodulatory signals. We have identified a novel conserved pathway that regulates dense-core vesicle maturation, as well as a novel G protein signal transduction pathway that controls the response to neuromodulatory signals.