NOTOX (267038)

  https://cordis.europa.eu/project/id/267038

  FP7 (2007-2013)

  Predicting long-term toxic effects using computer models based on systems characterization of organotypic cultures

  Systems biology for the development of predictive causal computer models. FP7-HEALTH-2010-Alternative-Testing-Strategies (HEALTH.2010.4.2-9-5)

  databases  ·  electron microscopy  ·  stem cells  ·  computational science  ·  mathematical model

  2011-01-01 Start Date (YY-MM-DD)

  2015-12-31 End Date (YY-MM-DD)

  € 9,699,961 Total Cost


  Description

NOTOX will develop and establish a spectrum of systems biological tools including experimental and computational methods for i) organotypic human cell cultures suitable for long term toxicity testing and ii) the identification and analysis of pathways of toxicological relevance. NOTOX will initially use available human HepaRG and primary liver cells as well as mouse small intestine cultures in 3D systems to generate own experimental data to develop and validate predictive mathematical and bioinformatic models characterizing long term toxicity responses. Cellular activities will be monitored continuously by comprehensive analysis of released metabolites, peptides and proteins and by estimation of metabolic fluxes using 13C labelling techniques (fluxomics). At selected time points a part of the cells will be removed for in-depth structural (3D-optical and electron microscopy tomography), transcriptomic, epigenomic, metabolomic, proteomic and fluxomic characterizations. When applicable, cells derived from human stem cells (hESC or iPS) and available human organ simulating systems or even a multi-organ platform developed in SCREENTOX and HEMIBIO will be investigated using developed methods. Together with curated literature and genomic data these toxicological data will be organised in a toxicological database (cooperation with DETECTIVE, COSMOS and TOXBANK). Physiological data including metabolism of test compounds will be incorporated into large-scale computer models that are based on material balancing and kinetics. Various “-omics” data and 3D structural information from organotypic cultures will be integrated using correlative bioinformatic tools. These data also serve as a basis for large scale mathematical models. The overall objectives are to identify cellular and molecular signatures allowing prediction of long term toxicity, to design experimental systems for the identification of predictive endpoints and to integrate these into causal computer models.


  Complicit Organisations

1 Israeli organisation participates in NOTOX.

Country Organisation (ID) VAT Number Role Activity Type Total Cost EC Contribution Net EC Contribution
France INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET AUTOMATIQUE (999547074) FR45180089047 participant REC € 0 € 382,909 € 0
Israel WEIZMANN INSTITUTE OF SCIENCE (999979306) IL520016858 participant HES € 0 € 218,832 € 0
Germany EURICE EUROPEAN RESEARCH AND PROJECT OFFICE GMBH (999778419) DE210372698 participant PRC € 0 € 233,576 € 0
Netherlands UNIVERSITEIT MAASTRICHT (999975911) NL003475268B01 participant HES € 0 € 350,871 € 0
France BIOPREDIC INTERNATIONAL SARL (997457015) FR21391701232 participant PRC € 0 € 168,237 € 0
Germany DEUTSCHES FORSCHUNGSZENTRUM FUR KUNSTLICHE INTELLIGENZ GMBH (999607602) DE148646973 participant REC € 0 € 327,343 € 0
Germany INSILICO BIOTECHNOLOGY AG (986299687) DE217410465 participant PRC € 0 € 330,576 € 0
Netherlands STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS (999984738) NL002562169B01 participant REC € 0 € 255,621 € 0
Sweden KAROLINSKA INSTITUTET (999978530) SE202100297301 participant HES € 0 € 500,525 € 0
United Kingdom Cambridge Cell Networks Ltd (996378666) nan participant PRC € 0 € 382,762 € 0
France CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS (999997930) FR40180089013 participant REC € 0 € 339,273 € 0
Germany FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ EV (998770686) DE124651626 participant HES € 0 € 280,524 € 0
Germany UNIVERSITAT DES SAARLANDES (999929545) DE138117521 coordinator HES € 0 € 1,078,931 € 0