Work in my lab is focused on understanding how signals in the brain lead to particular patterns of behavior. We utilize a combination of behavioral, genetic, biochemical, imaging, and electrophysiological techniques to study signaling in the brain of the worm C. elegans. Current projects include:
Excitation-Inhibition balance. We conducted systematic RNAi screens identifying 225 genes regulating synaptic transmission at neuromuscular junctions (NMJs). Current projects aim to determine how these genes alter synaptic transmission. We are particularly interested in genes that alter the balance between synaptic excitation (at cholinergic NMJs) and inhibition (at GABAergic NMJs). Characterizing these genes will provide new insights into how the excitation-inhibition balance is set. Changes in this balance are thought to play a role in cognitive and neurological disorders, e.g. autism and epilepsy.
Activity-dependent plasticity. We recently identified and are characterizing several forms of activity-dependent synaptic plasticity at the NMJ. For example, we identified a neuropeptide that induces a presynaptic form of potentiation. This peptide functions as part of a mechanosensory reflex that links muscle contraction to changes in ACh secretion at the NMJ. We also discovered a form of post-synaptic potentiation that occurs only in mutants lacking a cell surface Ig domain protein (IgSF). Thus, this IgSF protein prevents inappropriate potentiation of synapses, acting as an "antiplasticity" molecule.
Regulation of insulin and neuropeptide secretion. Insulin secretion, and its misregulation, plays a pivotal role in aging, diabetes, and obesity. We have developed assays for insulin secretion in intact worms. Using these assays, we are analyzing mechanisms regulating insulin secretion, and are pursuing genetic screens to identify genes required for insulin secretion.
microRNA regulation of synaptic transmission and synaptic development. We showed that the miRNA miR-1 alters synaptic transmission by regulating a retrograde signal from muscle that inhibits neurotransmitter release from motor neurons. Other miRNAs (the Let-7 family) regulate the timing of GABA synapse remodeling. We are currently characterizing miR-1 and Let-7 targets involved in these processes.
"We utilize a combination of behavioral, genetic, biochemical, imaging, and electrophysiological techniques to study signaling in the brain of the worm C."