SBIR Phase I: Expressing bacterial luciferase in zebrafish as an innovative new tool for data-intensive, higher-throughput drug discovery

This Small Business Innovation Research (SBIR) Phase I project proposes to develop self-generated bioluminescence in zebrafish to create improved models for new drug discovery, therapeutic testing, and biomedical disease imaging. Zebrafish share many common anatomical, developmental, and physiological features with humans, including disease pathologies and drug metabolism effects, and serve as ideal models for understanding how drugs and other chemicals facilitate disease management as well as cause harm through unidentified side-effects. The objectives of this research effort are to express the bacterial luciferase genes in zebrafish to create autonomously bioluminescent zebrafish models capable of delineating the biological and metabolic effects of human/drug interactions. The self-generation of bioluminescence in zebrafish is anticipated to enable higher-throughput screening assays to generate data in real time, faster, and in larger quantities than previously possible, thereby accelerating the pace of new drug discovery while reducing associated costs. The broader impact/commercial potential of this project, if successful, will be to improve pharmaceutical drug discovery and efficacy testing, and to facilitate better human and animal disease management. Small and rapidly growing zebrafish function to reduce space and maintenance requirements, thus lowering the costs associated with pharmaceutical research and new drug discovery while decreasing the industry's reliance on animals for laboratory testing. Scientific and technological understanding in the biomedical fields will be enhanced due to massively data-rich higher-throughput screening for drug action and disease therapies. Ancillary to these applications will be similar zebrafish screening strategies relevant to the detection and surveillance of chemical contaminants in the environment for the assurance of clean and safe water to better meet growing societal needs.