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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
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Engineered BRET-Based Biologic Light Sources Enable Spatiotemporal Control over Diverse Optogenetic Systems.
Kshitij Parag-Sharma, Colin P O'Banion1,2, Erin C Henry3
1Division of Chemical Biology and Medicinal Chemistry , UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.
ACS Synthetic Biology
|December 14, 2019
Summary
Researchers developed a novel bioluminescence resonance energy transfer-activated optogenetics (BEACON) system. This biologic light-driven approach overcomes limitations of external light sources for optogenetic control.
Area of Science:
- Optogenetics
- Biotechnology
- Molecular Biology
Background:
- Optogenetic systems provide precise control over biological processes.
- Current optogenetic methods rely on external light, requiring invasive procedures and causing phototoxicity.
- Limitations include heat production, photobleaching, and compromised cell viability.
Purpose of the Study:
- To develop a novel optogenetic system activated by biologic light.
- To overcome the limitations associated with external light sources in optogenetics.
- To enable spatially restricted and physiologically relevant optogenetic control.
Main Methods:
- Developed a novel BRET-activated optogenetics (BEACON) system.
- Utilized self-illuminating bioluminescent-fluorescent proteins to generate biologic light via bioluminescence resonance energy transfer (BRET).
- Tested the system's ability to activate various optogenetic tools.
Main Results:
- The BEACON system successfully activated common optogenetic systems.
- Activation was achieved in a spatially restricted manner.
- The system operated at physiologically relevant timescales, comparable to conventional light sources.
Conclusions:
- The BEACON system offers a novel, light-independent method for optogenetic control.
- Biologic light generation via BRET overcomes limitations of external illumination.
- This approach enhances cell and tissue viability for optogenetic applications.

