Work Package 1 - Bottom-up approach
The aims of our work in WP 1 are to decipher the effects of single and mixed exposure in cellular model systems, and to identify profiles of the biochemical transformation of perturbing compounds and affected molecular and signalling pathways as related to the internal chemical exposure. Large numbers of priority pollutants identified in WP 3 will be characterised with a panel of reporter gene assays that cover effects on all levels of the cellular toxicity pathway from metabolism to molecular initiating events, other adaptive stress responses to cytotoxic effects. Models rooted in the mechanisms of interaction of chemicals will be applied to interpret the effects of mixture studies, and bioinformatics tools will be applied for aggregating multivariate responses.
WP 1 will provide input to WP 3 for the adverse outcome pathway (AOP) identification through bioinformatics analyses of transcriptome and proteome signatures and integration with toxicokinetic information.