ABSTRACT

Animals ranging from fireflies to jellyfish produce light, a process known as bioluminescence. In nature, bioluminescence is used for prey capture, mate attraction and self-defense. This unique form of light production occurs when a small molecule combines with an enzyme to release photons. Researchers have harnessed this distinctive form of living light production for a wide variety of uses, from measuring activity in cells by tracking light flashes, to controlling activity in cells by transforming bioluminescent signals into electrical current flow. These tools are powerful for answering scientific questions, and may also prove useful as novel treatments, for example in stimulating specific areas of the brain or regulating heart pacemakers. This NeuroNex Technology Hub advances science by innovating new bioluminescent technologies, and teaching others about it. New innovations include the development of brighter chemical reactions, able to transmit signals farther across the brain, and the creation of new microscopes to harvest bioluminescent activity. The Technology Hub also helps other scientists learn both the principles and the pragmatic details of how to use these methods in their own research, through workshops, emissaries sent to laboratories, and a comprehensive website. An additional key focus of this project is on developing curricula for general education, from the grade school to the high school level, and on outreach projects within the broader community.

This NeuroNex Technology Hub enables bioluminescence use for cellular imaging and control. Historical impediments to effective bioluminescence use included the prolonged time scale of light production and long recharging time (severe limitations in early calcium imaging attempts), and insufficient light production. The Technology Hub and other recent advances directly address these concerns, for example through discovery of new molecules, development of novel strategies for conferring calcium sensitivity to bright and fast luciferases, and brightness amplification e.g., by resonant energy transfer. All these innovations not only serve imaging, but also enable bioluminescence as a driver for optogenetic molecules, a new cellular control strategy termed BioLuminescent OptoGenetics ('BL-OG'). While BL-OG has already proven effective as a solution that allows chemigenetic and optogenetic control in a single molecule, the advances implemented here significantly elaborate and improve this functionality. The Hub role in providing technology transfer to other practicing scientists is tailored to the individuals seeking training. This specificity in dissemination of pragmatic knowledge is achieved by designing workshops at Brown University around the needs of attendees, and through sending bioluminescence-trained technicians and students directly to laboratories to demonstrate and trouble-shoot experiments. The comprehensive website lists existing bioluminescent options, where they can be acquired, and aggregate bibliographic references. In all activities, the Hub team seeks active input from the user community to ensure that the knowledge being disseminated is of use to advancing the exact goals of practicing scientists. This NeuroTechnology Hub award is part of the BRAIN Initiative and NSF's Understanding the Brain activities.

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