Uncovering new approaches to manipulate and probe biochemical processes with spatial and temporal precision.

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While advances in imaging technologies are enabling scientists to observe cellular phenomena and protein complexes in increasingly greater detail, our ability to perturb and manipulate cells with equally fine precision have lagged. To better understand the dynamic cellular environment, tools that can selectively perturb biological processes, in real-time, with fast, reversible, tunable, and spatially- selective control are required. A major step forward in this area has come from the field of cellular optogenetics, wherein photosensory proteins are engineered to control various cellular processes with light. Because light can be delivered with fast temporal and subcellular spatial precision, such tools allow unprecedented biological control. In prior work, we developed novel optogenetic tools based on the plant photoreceptor cryptochrome 2 (CRY2), which can be used to precisely manipulate protein interactions, localization, and activity. While these tools have been successful at regulating protein function, improvements and new strategies for optogenetic regulation are needed. In the proposed work, we will usher in a new wave of optogenetic engineering, improving upon existing strategies, extending optogenetic tools into new areas, developing new photoreceptor modules, and testing novel engineering designs to regulate protein function with light. The long term goals of the project are to enable a set of modular precision tools for probing and manipulating biochemical processes with fast temporal control and over spatial scales ranging from subcellular to organismal.