Engineering a new class of optogenetic tools targeting small GTPases and kinases

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DESCRIPTION (provided by applicant): Our thought processes rely on networks of nerve cells called neurons. These networks must be properly formed during development and the neurons must be able to communicate correctly with each other for our brains to function normally. When neurological disorders occur, they can often be traced back to how one or a group of signaling proteins within neurons failed to perform. To understand how these proteins should have worked is not an easy task if one is limited to using traditional biochemical and genetic approaches, because the proteins often carry out different roles at different times and locations inside the cells. One powerful way to identify how the functions of these proteins depends on the location and timing of their activity would be to enable investigators to switch them on or off at precise times or locations inside the cells of intact neural circuits. The current proposal aims to generate a set of tools that can switch proteins on or off in living systems with a pulse of light. Knowledge gained with these tools can lead us one step closer to curing many neurological disorders. PUBLIC HEALTH RELEVANCE: The proposed studies will provide novel imaging tools that empower investigators to directly interrogate and understand the activities of specific signaling proteins at precise times and locations within specific types of neurons in vivo, the outcomes of which can provide mechanistic insights into the pathology and therapeutics of many neurological disorders, and may eventually unravel the molecular basis of intelligence, memory and learning.