Investigator, Full Prof (M) M_MOLBIO FACULTY, Mass General Research Institute

Professor of Neurobiology Harvard Medical School

autism; behavior patterns; brain signals; caenorhabditis elegans; caenorhabditis elegans proteins; endocytosis; exocytosis; motor neurons; neuropeptides; receptors ampa; receptors glutamate; synapses; synaptic defects; synaptic refinement; synaptic transmission

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:

Analysis of synaptic defects caused by mutations linked to autism

The synaptic adhesion molecules Neurexin and Neuroligin promote synapse formation and maturation and are linked to autism. We recently showed that the worm Neurexin and Neuroligin mediate a retrograde synaptic signal that regulates the kinetics of neurotransmitter release. We are now analyzing other autism linked genes to determine if they also play a role in this retrograde signal, or if they have similar effects on the kinetics of synaptic responses. Click here for more

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Regulation of SV exo- and endocytosis

We have done large scale RNAi screens to identify genes required for synaptic function. We identified identified a neuropeptide that induces a presynaptic form of potentiation. We described a novel biochemical mechanism for coupling SV exo- and endocytosis. And we have defined a molecular code that dictates the kinetics of neurotransmitter release. Click here for more

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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. Click here for more

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Neuropeptide regulation of a sleep-like state

During larval molts, worms undergo a period of profound behavioral quiescence, termed lethargus. We have identified neuropeptides that induce quiescence and arousal as part of this molting cycle. Current experiments aim to identify the circuit mechanisms leading to arousal and quiescence. Click here for more

Movies illustrating locomotion behavior during the L4-to-adult molt for wild type and npr-1 mutants.

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Activity-regulated synaptic refinement

We identified a transcription factor (HBL-1) that determines when during development, and which neuronal cell types undergo synaptic refinement. We also showed that HBL-1 expression levels are activity-regulated, which confers activity-dependence on this process. This work provides a simple genetic model for understanding critical period plasticity. Click here for more