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.

Public Health Relevance

Brain disorders take a great toll in the US and worldwide. Progress has been limited by the availability of tools to investigate neuronal circuits with temporal and special specificity until the development of optogenetics. Because current optogenetic tools are still limited in purpose our goal is to maximize the optogenetic toolkit by providing much-needed tools for the broad neuroscience community.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Molecular Neurogenetics Study Section (MNG)
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Freund, Michelle
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California Institute of Technology
Schools of Arts and Sciences
United States
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