WP 2 - Top-down approach
This WP aims at
- obtaining a comprehensive understanding on how environmental exposure is translated into chemical signals within humans and aquatic organisms,
- identifying exposome signatures correlating with adverse outcomes,
- characterizing signalling pathways perturbed in response to exogenous contaminants and endogenous stress signals, and
- understanding whether and how perturbed signalling pathways contribute to adverse outcomes.
In the human system we unravel exposome signatures in blood and urine samples of healthy and diseased individuals based on targeted and untargeted approaches. Novel methods for multi- and non-target screening in human matrices are developed. Besides exogenous contaminants and associated metabolites, endogenous metabolites such as mercapturic acids and stress-induced endogenous compounds are considered. Focusing on immune system-derived diseases (asthma & allergy, inflammatory lung diseases) and metabolic dysfunction, data from prospective epidemiological cohorts (LiNA, LISA) are used to link exposome signatures to perturbed signalling pathways and specific disease outcomes. Based on the integration of exposome, epigenome, transcriptome, and metabolome data hypotheses are developed regarding the molecular mechanisms underlying adverse health effects in response to environmental exposure and tested using experimental models in WP 1. Thereby we are particularly interested in exposure occuring in the prenatal period and early in life and the resulting consequences for disease development later in life including trans-generational effects.
In aquatic organisms such as fish and invertebrates we analyse the internal contamination in tissues as a driver for toxic effects and alterations in genetic diversity, biomarkers for health status of the organisms and the status of aquatic communities. Relationships between internal exposome signatures (compounds, concentrations, biomarkers) with external contamination in water and sediments are investigated. Using multi-target and non-target analytical approaches together with a broad range of bioassays exposome patterns as drivers of adverse effects are identified. These investigations are performed in close collaboration with IP Healthy Aquatic Ecosystems and the EU FP7 Collaborative Project SOLUTIONS (Grant no. 603437).