Modelling toxic responses in case studies for predictive human safety assessment (HeCaToS)

EU FP7 Project  with the objective to

• Develop an integrated modeling framework, by combining advances in computational chemistry and systems toxicology, for modelling toxic perturbations in liver and heart across multiple scales.
• Include vertical integrations of representations from drug(metabolite)-target interactions, through macromolecules/proteins, to (sub-)cellular functionalities and organ physiologies, and even the human whole-body level.
• In view of the importance of mitochondrial deregulations and of immunological dysfunctions associated with hepatic and cardiac drug-induced injuries, focus will be on these particular Adverse Outcome Pathways.
• Models will be populated with data from innovative in vitro 3D liver and heart assays challenged with prototypical hepato- or cardiotoxicants; data will be generated by advanced molecular and functional analytical techniques retrieving information on key (sub-)cellular toxic evens.
• For validating perturbed AOPs in vitro in appropriate human investigations, case studies on patients with liver injuries or cardiomyopathies due to adverse drug effects, will be developed, and biopsies will be subjected to similar analyses.

To the project, the FGCZ contributes Proteomics and Phospho-Proteomics analytical and data analysis / interpretation know-how and technology resources.