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

Objective

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.

Call for proposal

FP7-HEALTH-2010-Alternative-Testing
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Coordinator

UNIVERSITAT DES SAARLANDES
Address
Campus
66123 Saarbrucken
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 078 931
Administrative Contact
Claudia Schacht (Ms.)

Participants (12)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 339 273
Address
Rue Michel Ange 3
75794 Paris
Activity type
Other
Administrative Contact
Denis Fix (Mr.)
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS

Participation ended

Netherlands
EU contribution
€ 255 621,55
Address
Plesmanlaan 121
1066 CX Amsterdam
Activity type
Research Organisations
Administrative Contact
Henri Van Luenen (Dr.)
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 500 525
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Eva Gipperth
INSILICO BIOTECHNOLOGY AG
Germany
EU contribution
€ 330 576
Address
Meitnerstrasse 9
70563 Stuttgart
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Klaus Mauch (Mr.)
INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET AUTOMATIQUE
France
EU contribution
€ 382 909
Address
Domaine De Voluceau Rocquencourt
78153 Le Chesnay Cedex
Activity type
Research Organisations
Administrative Contact
Sandrine Lassout (Ms.)
DEUTSCHES FORSCHUNGSZENTRUM FUR KUNSTLICHE INTELLIGENZ GMBH
Germany
EU contribution
€ 327 343
Address
Trippstadter Strasse 122
67663 Kaiserslautern
Activity type
Research Organisations
Administrative Contact
Walter Olthoff (Dr.)
FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ EV
Germany
EU contribution
€ 280 524
Address
Ardeystrasse 67
44139 Dortmund
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jan Georg Hengstler (Prof.)
BIOPREDIC INTERNATIONAL SARL
France
EU contribution
€ 168 237
Address
Parc D'activite De La Breteche Batiment A4
35760 Saint Gregoire
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Li Ruoya (Dr.)
WEIZMANN INSTITUTE OF SCIENCE
Israel
EU contribution
€ 218 832
Address
Herzl Street 234
7610001 Rehovot
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Talia Tzahor (Ms.)
Cambridge Cell Networks Ltd
United Kingdom
EU contribution
€ 382 762
Address
St Johns Innovation Centre
CB4 0WS Cambridge
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Gordana Apic (Dr.)
EURICE EUROPEAN RESEARCH AND PROJECT OFFICE GMBH
Germany
EU contribution
€ 233 576
Address
Heinrich-hertz-allee 1
66386 St Ingbert
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Claudia Giehl (Ms.)
UNIVERSITEIT MAASTRICHT
Netherlands
EU contribution
€ 350 871,45
Address
Minderbroedersberg 4
6200 MD Maastricht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Willem Wolters (Mr.)