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., and his research team continued to investigate the response of killifish embryos to the ortho-substituted PCB, PCB- 153 (2,2’,4,4’,5,5’-hexachlorobiphenyl), one of the most abundant PCBs at the New Bedford Harbor (NBH) Superfund site. Embryos from the reference site Scorton Creek (SC) exposed to PCB153 exhibited mostly down-regulation in gene expression, especially genes involved in glucose metabolism. Such changes were not found in NBH embryos. The results suggest that PCB153 can disrupt glucose homeostasis but that NBH embryos are less sensitive to these effects, possibly because of genetic adaptation. Hahn and his research team also continued to characterize the four aryl hydrocarbon receptor (AHR) genes in killifish, to understand their role in the resistance to dioxin-like PCBs. Functional studies showed that the four AHR proteins encoded by these genes differ in the sensitivity and specificity of their interactions with different chemicals. The results suggest that they play different roles in the cell, providing clues to which ones may be involved in the long-term adaptation to PCBs and the NBH Superfund site. This year Hahn and his research team began looking more closely at another gene that may be involved in the mechanism of PCB resistance. Recent studies suggested that AHR-interacting protein (AIP) may be a candidate resistance gene. To learn more about AIP and its role in chemical effects in fish, the research team is using the revolutionary gene editing approach known as CRISPR-Cas9 to inactivate the gene in killifish and zebrafish. Initial results show that the team is able to edit the AIP gene in both species.