Molecular insights into the toxicology of trace elements in aquatic organisms using metallomic approaches

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Metal mining and smelting operations represent an important industrial and economic activity in Canada. These activities, which are expected to significantly increase with new mining projects in the vast but fragile northern ecosystems, release potentially toxic trace elements into freshwater environments. A key to the evaluation of the effects of such contaminants on aquatic organisms is the development of science-based ecological risk assessments (ERA), which link availability, bioaccumulation and toxicity of trace elements. Since little is known about how trace elements exert deleterious interactions with physiologically important biomolecules, a research program addressing this subject is of major importance. The long-term objective of the proposed research program is to understand how trace elements exert their toxic effects, at the molecular and cellular levels, and to elucidate the biochemical consequences of such effects. The proposed research will use two innovative approaches in the emerging area of environmental metallomic. The first approach involves the determination of the subcellular partitioning of trace elements in various aquatic organisms collected from metal-impacted environments. Such subcellular metal measurements will be performed to discriminate between (i) metals accumulated in the metal-sensitive compartment, which represents the proportion of accumulated metals responsible for adverse effects in living cells, and (ii) metals in the detoxified-metal compartment. The second complementary theme entails a detailed characterization of the sensitive biomolecules that play important biochemical and/or physiological roles, but are harmfully targeted by these toxic trace elements. Using state-of-the-art multidimensional analytical approaches, namely hyphenated techniques, metal complexes with such sensitive intracellular entities will be isolated, identified and quantified. This interdisciplinary research program, involving aspects of analytical chemistry, biochemistry, cellular biology and toxicology, will focus on metals of current interest (Cd, Hg, As, Ni, Tl and some rare earth elements). We also propose a comparative approach in terms of animal models and of geographical latitudes. Research at this level of integration will greatly advance our current state of knowledge of trace metal toxicity in organisms living in metal-contaminated aquatic environments. We anticipate that the results from this program will contribute to the development of improved models for environmental risk assessors to help them better understand and predict metal toxicity. The proposed research will involve training of students who will participate in national and international collaborations, benefit from internships in other labs and contribute to the expertise and knowledge in the field of environmental toxicology.