Brown University
Bioluminescence for Optimal Brain Control and Imaging

Bioluminescence (BL) is common in nature, especially in the ocean, and evolved many times for a variety of behaviors including prey capture, mate attraction, and self-defense. Light production occurs when a small molecule (luciferin) binds an enzyme (luciferase) and produces photons. This chemical form of light generation has many potential advantages for imaging brain activity and neural control.

Our Hub will systematically develop and disseminate novel and powerful bioluminescent tools for brain scienceand advance BL as a transformative tool in neuroscience through Innovation, Dissemination and Education. Hub-driven Innovation will greatly enhance BL control and imaging applications, widespread Dissemination of these new BL methods and related technologies will support their use across neuroscience, and Education will use this compelling biological phenomenon as a focus for an interdisciplinary curriculum for high school and undergraduate students.

Innovation will target improving the efficacy of BL light emission, an advance that can enable BL technologies broadly; expanding the applicability of BL to drive optogenetic sensors, including in an activity-dependent manner and for inter-neural communication; creating microscopes to image BL activity in vivo;and, elaboration of control and imaging BL methods to other key experimental models.

Key Research Resources Being Developed and Disseminated

This NeuroNex Technology Hub develops research resources enabling bioluminescence use for brain imaging and control. Key tools will be molecular constructs, viral vectors, imaging instrumentation, and experimental protocols for applying these resources in behaving experimental animals. Tool development is geared towards optimizing current and newly discovered luciferases serving as reporters of neural activity and as drivers of light sensing molecules controlling neural activity.New advances include discovery of novel molecules, brightness and speed amplification, developing novel strategies for conferring calcium sensitivity to bright and fast luciferases, and presynaptic targeting of luciferases. These innovations improve the functionality of bioluminescence as a driver for optogenetic molecules, a control strategy termed BioLuminescent OptoGenetics ('BL-OG'). While BL-OG has already proven effective as a solution that allows chemogenetic and optogenetic control in a single molecule, the advances implemented here significantly elaborate and improve this functionality.Importantly, they allow expanding the concept of BL-OG to neural activity-dependent and trans-synaptic control of brain activity. At the same time, these innovations serve imaging, augmented by creating novel in vivomicroscopes to monitor bioluminescence activity. Critical for impactful research resources, the application of novel tools will be thoroughly vetted through extensive applications in behaving animals, thus resulting in reliable protocols for bioluminescence brain control and imaging.  Lastly, our tools will drive expansion of bioluminescenceapplications across species and phyla.

We will develop best practices in Horizontal Open Science (sharing among scientists). We will develop and implement strategies for free and transparent exchange of tools and information that foments progress and collaboration among scientific disciplines. We will disseminate our protocols and tools via our Website. Further, we will host Workshops where other investigators can learn how to implement these tools in their own research. For hands-on, in-person instruction in their own laboratory, we will send Emissaries from our group to teach how to use the tools and techniques we have developed.  

We will develop best practices in Vertical Open Science (sharing across levels of understanding). We will use BioLuminescence outreach to energize science knowledge and appreciation in students and the public generally. We will develop and disseminate curricula for students at multiple levels, and host in-person training opportunities. We are planning High School Eventst o teach the biology, chemistry, and physics of BioLuminescence and its applications in neuroscience. We will host an annual Marine Biological Laboratory (MBL) Practicum for Undergraduatesin Woods Hole, MA. This weeklong course provides students from across the United States an opportunity to experience intensive, in-person training.

Reaching Out to the Community

You can find us on Twitter @BiolumHub and Instagram "biolumhub". 

Ute Hochgeschwender
Co-Principal Investigator
Nathan Shaner
Co-Principal Investigator
Diane Lipscombe
Co-Principal Investigator
Christopher Moore
Principal Investigator
Project Managers
Justine Allen
Program Manager
Krystal Literman
Administrative Assistant
Brown University
1 Prospect St
Providence, RI 02912