Optogenetic Dissection of Protein Kinase Networks

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Cell responses to external stimuli are controlled by numerous signaling pathways that are themselves interconnected to form signaling networks. Kinases are enzymes that carry out site-specific phosphorylation, the primary form of information transfer in signaling networks. SPARKLE is an approach to controlling the activity of kinases using light; genetically-encoded kinases are engineered to contain a caged lysine residue at their active site, and these enzymes then become active only after exposure to ultraviolet light. By using light to achieve spatial and temporal specificity in the activation of particular kinases, the activity of the cellular sub-networks controlled by these kinases can be dissected. With this approach it will be possible to elucidate cross-talk and feedback mechanisms between signaling pathways, and to define the role of particular pathways in driving the polarization and directed movement of cells. Broader Impacts: This project will provide interdisciplinary training in chemistry, cell biology, and computational modeling to undergraduate and graduate students. A new laboratory-based course in optogenetics will be developed, and outreach on the role of light in biological systems will be conducted at the Marbles Kids Museum in Raleigh.This award is supported jointly by the Cellular Dynamics and Function Cluster of the Molecular and Cellular Biosciences Division, and by the Chemistry of Life Processes Program of the Division of Chemistry.