Functional Omics of Native Fish Species for Improved Environmental Risk Assessment

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Current regulatory decision-making processes that aim to address the threats pollutants pose to aquatic ecosystems rely on standardized laboratory tests with select animal models. Recent studies (including those by my group) have shown that there is tremendous uncertainty associated with this approach resulting in inaccurate estimates of risks to native species of concern in local ecosystems, thus hampering decision-making. Also, the time, resources necessary and ethical concerns (use of large numbers of live animals) associated with current testing approaches render them impractical in context with current regulatory mandates that require testing of thousands of chemicals used by society. To address these issues, there are now increasing efforts to use mechanistic data in support of risk assessments as it can be generated more economically. One approach that has been proposed is that of the adverse outcome pathway (AOP). AOPs are conceptual frameworks that establish biologically plausible links between molecular perturbations and adverse outcomes of regulatory relevance. AOPs are applicable across species and are not chemical specific. To date, the development of AOPs relies on the generation of gene expression data using select model species. Due to the large number of regulatory steps that lead from the expression of a gene to a functional protein, however, it remains uncertain whether gene expression changes are truly predictive of alterations of proteins, which are a more consequential proxy for the fitness of an organism. This project will build on my past research and will establish advanced AOPs by integrating whole transcriptome with whole proteome analysis. These omics outcomes will then be linked with physiological and general health endpoints to assemble AOPs that will provide a quantitative and functional assessment of the alterations of molecular endpoints as indicators of impacts on the fitness of an organism. This will allow to identify critical genes that can be used as relevant biomarkers in the risk assessment of contaminants across fishes. Also, this combinatory analytical approach will provide novel insights into the translation of target genes to functional proteins under baseline and stressed conditions. To address the transferability of the research to species of interest in northern ecosystems 4 fishes native to Canada (rainbow trout, fathead minnow, lake trout and white sturgeon) will be studied. This project will focus on 3 chemicals of concern that are relevant to the oil and gas (benzo[a]pyrene), mining (selenium), and municipal wastewater (ethinylestradiol) sectors. The data and tools to be generated by this project will provide critical information for scientists, regulators and industry to meet their testing mandates because they will allow for more targeted, reliable, economic and ethical assessments of the risks contaminants pose to wildlife.