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Section: Partnerships and Cooperations

European Initiatives

FP7 & H2020 Projects

ERC Starting Grant SKIPPERAD, 2012-2017, Principal Investigator: M. Doumic.

This grant allowed to fund Sarah Eugène's Ph.D and M. Tournus's post-doc, as well as to develop the new collaborations with W-F. Xue in Canterbury and T. Teixeira in IBCP.

Collaborations in European Programs, except FP7 & H2020

NOTOX
  • Type: COOPERATION

  • Instrument: Integrated Project

  • Objectif: NC

  • Duration: January 2011 - December 2015

  • Inria contact: Dirk Drasdo

NOTOX developed and established 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 initially used 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 were 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 was removed for in-depth structural (3D-optical and electron microscopy tomography), transcriptomic, epigenomic, metabolomic, proteomic and fluxomic characterisations. Together with curated literature and genomic data the toxicological data was organised in a toxicological database (cooperation with DETECTIVE, COSMOS and TOXBANK). Physiological data including metabolism of test compounds have been 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 served 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.

Inria contributions were multilevel and multiscale models of drug toxicity and its consequences on ammonia detoxification and are detailed in the result section on liver modeling. Webpage: http://notox-sb.eu/fp7-cosmetics-europe/

Collaborations with Major European Organisations

  • U. Klingmüller: DKFZ (German Cancer Research Centre), Department for Systems Biology (Germany)

  • Role of HGF in liver regeneration. Lung cancer.

  • K. Breuhahn: University Hospital of Heidelberg, Pathology (Germany)

  • Lung cancer invasion. Role of HGF in liver regeneration.

  • JG Hengstler: Leibniz Center, IfADo (Germany)

  • Liver research, toxicology, regeneration.

  • University of Leipzig, Interdisciplinary center for bioinformatics (Germany)

  • Projects on tissue regeneration, software