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Bioluminescent Zebrafish

Autobioluminescent zebrafish for endocrine disrupting chemical detection

Funded by the National Institutes of Health and National Institute of Environmental Health Sciences

The objective of this NIH-funded research project is to transition ongoing work with autonomous bioluminescence in yeast and human cell lines to the whole organism level to create an autobioluminescent zebrafish to facilitate the screening and environmental surveillance of endocrine disrupting chemicals (ECDs). EDCs interfere with endogenous hormones that control virtually every organ and system in the human body and elicit consequent developmental and reproductive effects that are of significant human health concern.

Major screening programs have been established worldwide to identify and describe the actions of chemicals with EDC characteristics, but the process is challenging because of the need to characterize complex EDC modes of action superimposed against an equally complex organismal network of hundreds of circulating hormones that exert widespread tissue/organ-, age-, and sex-specific effects. Whole-organism in vivo assays are considered more ideally suited for acquiring this information, with the zebrafish serving as a premier model for doing so. However, the in vivo imaging potential of zebrafish is not being fully realized due to the inability to effectively bioimage throughout the zebrafish lifecycle.

Despite its various genetic optimizations, green fluorescent protein and its other color variants remain prone to high levels of background fluorescence under live imaging conditions due to excitation of endogenous chromophoric material within the zebrafish tissue as they age, thereby limiting all fluorescent phenotypic screens to the zebrafish embryonic stage. Zebrafish transgenics that integrate bioluminescent reporter systems may solve this problem because zebrafish do not display natural bioluminescence and therefore present superior signal-to-noise ratios. Particularly, the synthetic bacterial luciferase reporter is capable of self-synthesizing all of the substrates required for the production of light when introduced as a complete operon, and therefore operates autonomously and in real-time to bioindicate cellular and molecular pathways and mechanisms coupled to bioluminescent outputs.

This project leverages the synthetically optimized bacterial luciferase bioluminescent reporter cassette to the whole organism level to develop a new in vivo transgenic zebrafish model for real-time, tissue-specific bioluminescence-based EDC screening across all zebrafish life stages.

Seeing Things in a New Light” in Quest magazine.

For more information, contact Tingting Xu at txu2@utk.edu or 865-974-8369.

 

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