Interrogating Physiological Functions with Light and Chemicals.

Abstract

Optogenetics and chemogenetics have transformed how physiologists interrogate biological systems by enabling precise control over protein activity and cellular function. Optogenetics uses light-sensitive proteins for rapid and localized control, while chemogenetics employs small molecules to trigger or block specific pathways with systemic and sustained effects. These tools have advanced research in areas such as brain function, heart rhythm, immune response, and gene regulation. They have been applied to disease models that include epilepsy, metabolic and cardiovascular diseases, immunoinflammatory disorders, and cancer. Clinical applications are emerging, such as optogenetic therapies for vision restoration and chemogenetic safety switches in engineered immune cells. In this review, we categorize these tools by their mechanisms of action, compare their advantages and limitations, and discuss strategies to improve their precision, efficiency, and translational capability. As these technologies continue to evolve, they offer powerful approaches to dissect complex physiological processes and drive innovative therapeutic interventions.