dCod 1.0: decoding the systems toxicology of Atlantic cod (Gadus morhua).

The Atlantic cod (Gadus morhua) is an important species in North Atlantic fisheries, as well as coastal and pelagic ecosystems. It is also a widely used indicator species in European monitoring programs. The goal of the dCod 1.0-project is to combine competencies in environmental toxicology, biology, bioinformatics and mathematics across the traditional department boundaries, to create a deeper understanding of the Atlantic cod's adaptations and reactions to stressors in the environment. Building on thorough studies and mapping of the cod genome and long research traditions on the physiology, toxicology and reproduction biology of cod, the dCod project will expand our knowledge with genomics based methods, with studies of how the cod genome responds under different environmental conditions.

In dCod 1.0 we have so far generated large amounts of experimental samples and data using in silico (defensome modelling and metabolic reconstruction), in vitro (luciferase reporter assays with cod nuclear receptors and aryl hydrocarbon receptors), ex vivo (precision-cut liver slices), aquaria and field studies, as data sets for bioinformatics analyses and mathematical models that can describe responses based on different scenarios. Overall, the ambition is to create a knowledge-base and a tool for environmental monitoring and risk assessment. The project involves several lab and field studies, large and comprehensive omics analyses, and transdisciplinary activities.

It is the aim of systems toxicology to integrate large datasets from environmental genomics (transcriptomics, proteomics, metabolomics) into meaningful representations of the toxic response, by using computational methods to detect enriched pathways, networks and interactions, and ultimately to develop mathematical models that can be used to predict adverse outcomes of specific exposures and mixtures. Phenotypic anchoring represents a process of determining the relationship between a particular toxicogenomic expression profile and the pathological or physiological phenotype of the organism for a particular exposure or dose and at a particular time. Studies performed in our group with Atlantic cod indicate that several environmental contaminants display effects related to lipid metabolism and other pathways connected with energy storage and generation. Hence, a phenotypic result of such effects may be reflected in growth rates of individual fish, or biomass of cod populations. Such effects, although subtle at the individual level, may have important economic effects if transformed into effects on biomass or recruitment in harvested fish stocks. The bold and ambitious aim of the dCod project is to generate sufficient insight into the systems biology of Atlantic cod to be able to model effects of contaminants on growth rates and reproduction.