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Duke University

Superfund Research Program

Neurobehavioral and Bioenergetic Consequences of Evolving Resistance to Polycyclic Aromatic Hydrocarbons in a Multi-Stressor Environment

Project Leader: Nishad Jayasundara
Grant Number: P42ES010356
Funding Period: 2022-2027
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2022-2027)

The overarching goal of the Duke Superfund Research Center (DUSRC) is to determine later life consequences of early life exposure to polycyclic aromatic hydrocarbons (PAHs) and heavy metals. In accordance with the Superfund Mandate on understanding epidemiological and ecological impacts of exposure to hazardous chemicals, this project addresses ecological outcomes of PAH and metal exposure in an evolutionary toxicology context.

Evolved resistance to hazardous contaminants has far reaching implications for environmental health, ecological risk assessment, and management. However, key knowledge gaps exist in the understanding of the mechanisms of pollution adaptation and fitness consequences, especially when animals are exposed to multiple chemicals (simultaneous or sequential) and other abiotic stressors in their natural environment. Addressing these gaps, the team extends their extensive previous research on evolved resistance to PAHs in Atlantic killifish Fundulus heteroclitus in the Elizabeth River (ER), VA, in a new direction. Specifically, they are elucidating the role of mitochondria as an important target of PAHs and metals during early development in mediating adverse behavioral and bioenergetic outcomes later in life and in subsequent generations under optimal and suboptimal thermal and dissolved oxygen conditions.

The project’s specific aims are:

  • To determine later life fitness consequences of early life simultaneous exposures to PAHs and cadmium (Cd) and lead (Pb).
  • To elucidate later life and cross generational fitness consequences of developmental exposures to PAHs and subsequent Cd or Pb exposure and determine links to epigenetic modifications.
  • To compare the gut microbiome differences in PAH-resistant and sensitive fish, and elucidate the potential contributions of the gut microbiome on PAH resistance using germ-free killifish studies.
  • To develop an ecological-effect directed analysis based on medium-throughput mitochondrial and behavioral assays to assess toxicity of environmental samples including remediated samples derived in the Microencapsulation Delivery Vehicles for the Implementation of Precision Bioremediation at PAH-Contaminated Superfund Sites project.

Moreover, they bi-directionally collaborate with the Persisting Neurobehavioral Dysfunction Caused by Interacting Toxicant Exposures During Development: Mechanistic and Treatment Studies with Zebrafish and Rats (behavioral studies) and Mitochondrial and Cellular Mechanisms of Neurotoxicity of Superfund Chemical Co-exposures (mitochondrial studies) projects, focusing on aspects of experimental design and toxicity mechanisms. They also work closely with the Community Engagement Core for dissemination of findings to the relevant communities, the Data Management and Analysis Core for experimental design, data management and analyses, and the Analytical Chemistry Core for chemical analyses. The project is heavily involved in the training of graduate students and post-doctoral researchers and coordinates activities with the Research Experience and Training Coordination Core as well as the Administrative and Research Translation Core for overall support and research translation.

Overall, studies elucidate ecologically relevant fitness outcomes of PAH and metal exposures and selected aspects of underlying molecular mechanisms in killifish populations, while rendering the toxicity assays for characterizing effectiveness of remediation. Novel areas of research include elucidating PAH and metal interactive effects, discerning the role of the gut microbiome in PAH resistance, and developing an ecologically relevant toxicity analyses based on killifish behavior and energetics that target SRP’s Mandate 3 to inform ecological risk assessment.

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