Thermogenetic control of Ca²⁺levels in cells and tissues

ABSTRACT Virtually all major processes in cells and tissues are regulated by calcium ions (Ca 2+ ). Understanding the influence of Ca 2+ 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 Ca 2+ manipulation are limited with respect to response time, and tissue penetration depth. Here we present G enetically E ncoded C alcium Co ntroller ( GECCO ), a system for thermogenetic Ca 2+ 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 Ca 2+ signals. GECCO enabled the shaping of insulin release from β-cells, the identification of drugs that potentiate Ca 2+ -induced insulin release, and the generation of synthetic Ca 2+ signatures in plants.