Natural photoreceptors and their application to synthetic biology

• We need precision technologies for perturbing specific cellular signaling pathways.
• New technologies have emerged that use light for perturbing cellular processes.
• We describe the design principles of natural photoreceptors.
• We review how these principles are applied to synthetic signaling systems.

The ability to perturb living systems is essential to understand how cells sense, integrate, and exchange information, to comprehend how pathologic changes in these processes relate to disease, and to provide insights into therapeutic points of intervention. Several molecular technologies based on natural photoreceptor systems have been pioneered that allow distinct cellular signaling pathways to be modulated with light in a temporally and spatially precise manner. In this review, we describe and discuss the underlying design principles of natural photoreceptors that have emerged as fundamental for the rational design and implementation of synthetic light-controlled signaling systems. Furthermore, we examine the unique challenges that synthetic protein technologies face when applied to the study of neural dynamics at the cellular and network level.