Engineering Microbial Opsins for Neuroscience via Structure-Guided Recombination

California Institute Of Technology, Pasadena CA

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Abstract

DESCRIPTION (provided by applicant): Microbial opsins are light-sensitive proteins that can be expressed in specified cells via targeting promoters and turned on/off with millisecond speed, thus providing genetic and optical ('optogenetic') control of cell function with high spatial and temporal specificity. Their ability to control the electrical activity of neural circuits and confe reversible gain and loss of function of specific neuronal phenotypes allows us to study neural systems and diseases in unprecedented manner. Optogenetic research today, however, relies on a limited set of natural microbial opsins with broad activation spectra, limited ion selectivity and a narrow range of kinetics. We are proposing a novel approach to opsin engineering that capitalizes on the power of structure-guided protein engineering and directed evolution. In parallel, we will also search for novel naturally occurring opsins in niche environments. The expanded optogenetic toolkit will facilitate the investigation of neuronal circuits in health and disease.