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

Objetivo

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.

Convocatoria de propuestas

FP7-HEALTH-2010-Alternative-Testing
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Coordinador

UNIVERSITAT DES SAARLANDES
Dirección
Campus
66123 Saarbrucken
Alemania

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Claudia Schacht (Ms.)
Aportación de la UE
€ 1 078 931

Participantes (12)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Francia
Aportación de la UE
€ 339 273
Dirección
Rue Michel Ange 3
75794 Paris

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Tipo de actividad
Research Organisations
Contacto administrativo
Denis Fix (Mr.)
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS

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Países Bajos
Aportación de la UE
€ 255 621,55
Dirección
Plesmanlaan 121
1066 CX Amsterdam

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Tipo de actividad
Research Organisations
Contacto administrativo
Henri Van Luenen (Dr.)
KAROLINSKA INSTITUTET
Suecia
Aportación de la UE
€ 500 525
Dirección
Nobels Vag 5
17177 Stockholm

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Eva Gipperth
INSILICO BIOTECHNOLOGY AG
Alemania
Aportación de la UE
€ 330 576
Dirección
Meitnerstrasse 9
70563 Stuttgart

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Tipo de actividad
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contacto administrativo
Klaus Mauch (Mr.)
INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET AUTOMATIQUE
Francia
Aportación de la UE
€ 382 909
Dirección
Domaine De Voluceau Rocquencourt
78153 Le Chesnay Cedex

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Tipo de actividad
Research Organisations
Contacto administrativo
Sandrine Lassout (Ms.)
DEUTSCHES FORSCHUNGSZENTRUM FUR KUNSTLICHE INTELLIGENZ GMBH
Alemania
Aportación de la UE
€ 327 343
Dirección
Trippstadter Strasse 122
67663 Kaiserslautern

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Research Organisations
Contacto administrativo
Walter Olthoff (Dr.)
FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ EV
Alemania
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€ 280 524
Dirección
Ardeystrasse 67
44139 Dortmund

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Jan Georg Hengstler (Prof.)
BIOPREDIC INTERNATIONAL SARL
Francia
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€ 168 237
Dirección
Parc D'activite De La Breteche Batiment A4
35760 Saint Gregoire

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Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contacto administrativo
Li Ruoya (Dr.)
WEIZMANN INSTITUTE OF SCIENCE
Israel
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€ 218 832
Dirección
Herzl Street 234
7610001 Rehovot

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Talia Tzahor (Ms.)
Cambridge Cell Networks Ltd
United Kingdom
Aportación de la UE
€ 382 762
Dirección
St Johns Innovation Centre
CB4 0WS Cambridge

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Tipo de actividad
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contacto administrativo
Gordana Apic (Dr.)
EURICE EUROPEAN RESEARCH AND PROJECT OFFICE GMBH
Alemania
Aportación de la UE
€ 233 576
Dirección
Heinrich-hertz-allee 1
66386 St Ingbert

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Tipo de actividad
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contacto administrativo
Claudia Giehl (Ms.)
UNIVERSITEIT MAASTRICHT
Países Bajos
Aportación de la UE
€ 350 871,45
Dirección
Minderbroedersberg 4
6200 MD Maastricht

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Willem Wolters (Mr.)