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Thermogenetic control of Ca2+ levels in cells and tissues

Ermakova, Y. G.; Waadt, R.; Ozturk, M. S.; Roshchin, M.; Lanin, A. A.; Chebotarev, A.; Pochechuev, M.; Pak, V.; Kelmanson, I.; Smolyarovasmol, D.; Keutler, K.; Matyushenko, A. M.; Tischer, C. V.; Balaban, P. M.; Nikitin, E. S.; Schumacher, K.; Zheltikov, A.; Prevedel, R.; Schultz, C.; Belousov, V. V.

2023-03-22 synthetic biology
10.1101/2023.03.22.533774 bioRxiv
Show abstract

Virtually all major processes in cells and tissues are regulated by calcium ions (Ca2+). Understanding the influence of Ca2+ on cell function requires technologies that allow for non-invasive manipulation of intracellular calcium levels including the formation of calcium patterns, ideally in a way that is expandable to intact organisms. The currently existing tools for optical and optogenetic Ca2+ manipulation are limited with respect to response time, and tissue penetration depth. Here we present Genetically Encoded Calcium Controller (GECCO), a system for thermogenetic Ca2+ manipulation based on snake TRP channels optically controlled by infrared illumination. GECCO is functional in animal and plant cells and allows studying how cells decode different profiles of Ca2+ signals. GECCO enabled the shaping of insulin release from {beta}-cells, the identification of drugs that potentiate Ca2+-induced insulin release, and the generation of synthetic Ca2+ signatures in plants.

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