# Project 4: Neurobehavioral and bioenergetic consequences of evolving resistance to polycyclic aromatic hydrocarbons in a multi-stressor environment

> **NIH NIH P42** · DUKE UNIVERSITY · 2022 · $274,836

## Abstract

Abstract
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, DUSRC-Project 4 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 our
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, we extend our extensive previous research on evolved resistance to PAHs
in Atlantic killifish Fundulus heteroclitus in the Elizabeth River (ER), VA, in a new direction. Specifically, we will
elucidate 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. Our specific aims are: Aim 1 – to determine
later life fitness consequences of early life simultaneous exposures to PAHs and Cd and Pb; Aim 2 – 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; Aim 3 – 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; Aim 4 – 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 DUSRC-Project 5. Moreover, we will bi-directionally collaborate with
Project 2 (behavioral studies) and Project 3 (mitochondrial studies), focusing on aspects of experimental design
and toxicity mechanisms. We will also work closely with the community engagement core for dissemination of
our findings to the relevant communities, the data management core for experimental design, data management
and analyses, and the analytical chemistry core for chemical analyses. The project will be heavily involved in the
training of graduate students and post-doctoral researchers and will coordinate activities with the training core
as well as the admin core for overall support and research translation. Overall, studies will 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...

## Key facts

- **NIH application ID:** 10353154
- **Project number:** 2P42ES010356-20
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Nishad Jayasundara
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $274,836
- **Award type:** 2
- **Project period:** 2000-06-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353154

## Citation

> US National Institutes of Health, RePORTER application 10353154, Project 4: Neurobehavioral and bioenergetic consequences of evolving resistance to polycyclic aromatic hydrocarbons in a multi-stressor environment (2P42ES010356-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10353154. Licensed CC0.

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