Superfund Research Program
Mechanisms and Impacts of PCB Resistance in Fish
Project Leader: Mark E. Hahn (Woods Hole Oceanographic Institution)
Co-Investigators: Sibel I. Karchner (Woods Hole Oceanographic Institution), Neelakanteswar Aluru (Woods Hole Oceanographic Institution)
Grant Number: P42ES007381
Funding Period: 1995-2020
This year, Mark E. Hahn, Ph.D., Sibel Karchner, Ph.D., and Neel Aluru, Ph.D.; EPA collaborators; and colleagues continued research to understand molecular mechanisms involved in evolved resistance to polychlorinated biphenyls (PCBs) and related chemicals in populations of the Atlantic killifish (Fundulus heteroclitus). The research team followed up their recent identification of aryl hydrocarbon receptors (AHRs) and AHR-interacting protein (AIP) as shared targets of selection in populations of PCB-resistant killifish (Reid et al., 2016) by characterizing AIP single-nucleotide polymorphisms (SNPs) and by using CRISPR-Cas9 genome-editing technology to generate loss-of-function alleles of killifish and zebrafish AHRs and AIP. They generated, and are characterizing, germ-line AIP-mutant zebrafish. An important milestone was reached when they identified heterozygous and homozygous mutants of AHR2a, AHR2b, and AIP in F2 descendants (grandchildren) of killifish that had been subjected to gene-targeting by CRISPR-Cas9 as embryos in 2014 (AHRs) and 2016 (AIP). In additional studies, they used a metabolomics approach to compare fish from PCB-sensitive and PCB-resistant populations (Glazer et al., 2018), collaborated with the Environmental PPAR-gamma Pathway Activators: Multifaceted Metabolic Disruptors Impacting Adipose and Bone Homeostatsis Project and Research Translation Core to investigate altered lipid homeostasis in PCB-resistant killifish (Crawford et al., 2019 submitted), and collaborated with the University of Rhode Island SRP in a study of air pollutants detected by passive sampling (McDonough et al., 2019). Overall, this research is helping them to understand how natural populations of animals are affected by long-term exposure to toxic chemicals in the environment. The research applies innovative molecular approaches in an ecological context to understand chemical-induced evolutionary changes in signaling pathways in response to multi-generational, early-life exposure to Superfund chemicals.