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dCod 1.0: Decoding the systems toxicology of Atlantic cod (Gadus morhua)
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Anders Goksøyr
Department of Biological Sciences, University of Bergen

The dCod 1.0 project is part of the Center for Digital Life Norway (), a large transdisciplinary research and training initiative under the BIOTEK2021 program of the Research Council of Norway. 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 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, where studies of how the cod genome responds under different environmental conditions will be investigated.

dCod 1.0 is generating large amounts of experimental samples and data using in vitro (luciferase reporter assays), 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. Another approach is in silico mapping of the chemical defensome. The chemical defensome comprises an integrated network of gene families and pathways that together function to metabolize and eliminate harmful compounds. Using network analysis and graph theory methods, we have identified central nodes and protein-protein interactions and processes within the defensome network. Moreover, the cod defensome network was used in analysis of toxicogenomic data in order to look for patterns beyond individual pathway enrichment analyses. As an important receptor for a wide range of drugs and environmental pollutants, vertebrate nuclear receptor PXR (NR1I2) regulates the transcription of a number of genes involved in the biotransformation of xenobiotics, including cytochrome P450 enzymes (CYP). We have shown that the pxr gene is absent in the cod genome, and we have found compelling evidence for multiple independent losses of the pxr gene in vertebrate evolution which accentuates the need for understanding how the chemical defensome system has evolved in teleost fish.

The dCod 1.0 project () is funded under the Digital Life Norway initiative of the BIOTEK2021 program (project no. 248840).

Chairperson: Ruth Brenk, Department of Biomedicine

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