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Autonomously-activating bioluminescent reporters to enable continuous, real-time, non-invasive brain cell imaging

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43MH118186-01
Agency Tracking Number: R43MH118186
Amount: $150,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 101
Solicitation Number: PAR15-091
Timeline
Solicitation Year: 2015
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-07-01
Award End Date (Contract End Date): 2019-06-30
Small Business Information
2450 EJ CHAPMAN DR
Knoxville, TN 37996-0001
United States
DUNS: 968832498
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 GARY SAYLER
 (865) 974-8080
 sayler@utk.edu
Business Contact
 STEVEN RIPP
Phone: (865) 604-7713
Email: steven.ripp@490biotech.com
Research Institution
N/A
Abstract

Autonomously activating bioluminescent reporters to enable continuousreal timenoninvasive brain cell imaging
Project Summary
This Small Business Innovation ResearchSBIRPhase I project proposes to develop a set of genetically encodedself exciting bioluminescentautobioluminescentoptical imaging reporters that will enable continuous neuron
and astrocyte specific imaging without perturbing endogenous cellular metabolismwhile using common
laboratory equipmentThe treatment and management of brain disorders imposes enormous financial and social
costsThe NIH therefore launched the BRAIN initiative to develop a new generation of innovative research tools
and therapies that enable brain cell specific imagingspatiotemporal trackingand continuousnon invasive cell
monitoring to facilitate new methods for evaluating brain cell physiology and new means to identify relative
connectivityThe current generation of brain cell imaging toolswhich rely on fluorescent and luciferin luciferase
bioluminescent chemistriesare incapable of achieving the NIH BRAIN initiative s goalsFluorescent imaging
modalities require an excitation light to trigger their emission signalThis excitation is difficult to deliver to the
brain and causes high levels of background autofluorescence that restricts signal discriminationBioluminescent
imagingwhich has a greater signal to noise ratio due to a lack of background bioluminescence in tissueis
similarly limited in that it can only produce an emission signal in the presence of an externally supplied substrateluciferinRepeated application of this substrate results in discontinuous signaling and substrate distribution
kinetics that are challenging to replicateThereforeto meet the needs of the NIH BRAIN initiative and overcome
the limitations restricting existing brain cell imaging toolsBioTech will reengineer our synthetic
autobioluminescent genetic operon to create a new type of reporting technology that requires no external
stimulatione glight or luciferin substrateto provide continuousnon invasivebrain cell specific optical
monitoringThe genetic topology of the synthetic autobioluminescent operon will be systematically optimized to
maximize signal output and minimize its effects on the host brain cell s metabolismUsing this technologyneuron and astrocyte specific autobioluminescent differentiation reporter platforms will be developed that will
enable researchers to track the onset of brain cell differentiation and the subsequent fate of descendant cellsThese autobioluminescent brain cell specific technologies will be validated usingD cell culture to demonstrate
their utility and generate proof of principle dataAt the conclusion of this project we will deliver a set of genetic
constructs endowing brain cell specificcontinuously autobioluminescent phenotypes that researchers can
utilize to continuously and non invasively label and track cellular locationphysiologyand connectivity Project Narrative
Brain disorders result from a variety of causes that each require different diagnosistreatmentand palliative
care approaches that impose enormous financial and social costsResearch aimed at lowering these costs and
improving outcomes by investigators from across diverse fieldssuch as genetic engineeringstem cell
culture differentiationregenerative medicineand tissue engineeringis hindered by the unavailability of
methods to continuously track specific brain cellsor groups of brain cellsto discern their function in healthy
and diseased statesTo overcome these limitations and address the needs of the NIH BRAIN initiativeBioTech will develop a set of self excitingcontinuously bioluminescent optical imaging reporters thatunlike
existing systemsare pre engineered to support genetically encodedautonomousmetabolically neutralneuron
or astrocyte specific bioluminescent expression that can be monitored with common laboratory equipment

* Information listed above is at the time of submission. *

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