Objective

To define the mechanisms of PAH toxicity via the zebrafish assay

Activities
  • Determine the phenotypic and neurobehavioral impacts of embryonic exposure to individual environmentally relevant PAHs, complex mixtures, and environmentally transformed PAHs and define the role of AHRs in the response.
  • Apply next-generation sequencing to identify the early developmental biomarkers of PAH exposure to individual environmentally relevant PAHs, complex mixtures, and environmentally transformed PAHs.
  • Define the long-lasting impacts of embryonic exposure to individual environmentally relevant PAHs, complex mixtures, and environmentally transformed PAHs on the adult cardiovascular and central nervous system.

Major Accomplishments
  • Developed a highly predictive AHR ligand binding model for in silico prediction of PAH binding to human and zebrafish AHRs.
  • Developed the first zebrafish AHR null fish.
  • Determined that benz(a)anthracene and dibenzothiophene have distinct mechanisms of toxicity.
  • Implemented high-throughput in vivo zebrafish screening assays to allow assessment of an unlimited number of complex mixtures.
  • Discovered that oxy-PAHs, present at Superfund sites, are more toxic than parent PAHs.

Project-Generated Resources

The gene expression data will be shared. The project uses the NCBI Gene Expression Omnibus to disseminate the raw data files. After we expand the AHR2 KO line in our facility, we will submit it to The Zebrafish Model Organism Database (ZFIN) for their propagation. We will also make the SPF lines freely available as sufficient brood stocks are available at the SARL.

People
  • Robert Tanguay, Leader
  • Michael Simonich, Research Associate
  • Greg Gonnerman, Senior Faculty Research Assistant
  • Mitra Geier, Graduate Student

SARL Microsporidia Free Zebrafish Order Form
Sinnhuber Aquatic Research Laboratory (SARL)


Articles and Resources