Neural circuit development and plasticity:
Our research focuses on understanding neural circuits - the functionally connected neurons that give rise to thought and behavior. We are particularly interested in how neurons build appropriate synaptic connections and modulate their strength.
Synapses comprise a presynaptic active zone that is responsible for the calcium-dependent release of neurotransmitter-filled synaptic vesicles in response to action potentials. This signal is received by neurotransmitter receptors that cluster opposite active zones at postsynaptic densities. Synapse formation is a complex process that depends on intercellular communication between pre and postsynaptic cells – often at sites very distant from cell bodies. In fact, a single central neuron can form thousands of synapses and must independently regulate the development of each. Synapses must also maintain the lifelong ability to modify their morphology and physiology in response to environmental stimuli and changes in activity levels – modifications that are thought to underlie learning and memory.
Defects in synaptic development and plasticity are associated with a broad range of neurological disorders including developmental disorders such as autism; motor, cognitive and psychological impairments; and neurodegeneration. Thus, the identification and characterization of the molecules that regulate synapse formation and function is key to our understanding of normal neural function and our ability to treat a variety of neurological disorders.
We are also developing genetic technologies for identifying and gaining genetic control of neuronal subtypes to determine their characterize their roles in neural circuits. Working with the laboratories of Jill Wildonger and Melissa Harrison, we recently adapted the CRISPR/Cas9 system for use in Drosophila. CRISPR is a novel technique that is revolutionizing genome engineering. Developed from bacteria where the CRISPR/Cas9 system functions in acquired immunity, CRISPR technology enables highly efficient and specific editing of targeted genomic sequences – opening the door to routine genome engineering. The many applications of CRISPR technology include modifying the genomes of model organisms to probe gene function, conferring disease resistance to agricultural organisms, and correcting disease-causing mutations in humans. We are capitalizing on this advance to develop novel genome engineering approaches that overcome current technological limitations to understanding neural circuits. Visit our flyCRISPR and flyCRISPR Optimal Target Finder sites for more details on our genome engineering work.