Superfund Research Program
Mechanisms and Impacts of PCB Resistant 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 Hahn, Ph.D., Sibel Karchner, Ph.D., Neel Aluru, Ph.D., and EPA and BUSRP collaborators continued research to understand molecular mechanisms involved in evolved resistance to PCBs and related chemicals in populations of the Atlantic killifish (Fundulus heteroclitus). They followed up on 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 Science 354: 1305) by using CRISPR-Cas9 genome-editing technology to generate loss-of-function alleles of killifish and zebrafish AHRs and AIP. Complete loss of AIP function in zebrafish (homozygous null alleles; two lines) did not affect early development but caused complete mortality by 12 days post fertilization. Prior to that, the AIP-null fish displayed reduced sensitivity to the developmental toxicity of a PCB and a dioxin. In additional studies, they collaborated with BUSRP members involved in the Environmental PPAR-gamma Pathway Activators: Multifaceted Metabolic Disruptors Impacting Adipose and Bone Homeostasis Project and Research Translation Core to investigate altered lipid homeostasis and effects of tributyl tin in PCB-resistant killifish (Crawford et al. 2019, 2020). They also engaged in international collaborations to investigate the properties of AHRs in other fish species that exhibit reduced sensitivity to some dioxin-like compounds (Zhang et al. 2019a, 2019b; Aranguren-Abadia et al. 2020). Overall, the research in conducted under this project is helping us 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.