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Hepatic and Cardiac Toxicity Systems modelling

Objective

HeCaToS aims at developing integrative in silico tools for predicting human liver and heart toxicity. The objective is 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. This framework will 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. Existing ChEMBL and diXa data infrastructures will be advanced for data gathering, storing and integrated statistical analysis. Model performance in toxicity prediction will be assessed by comparing in silico predictions with experimental results across a multitude of read-out parameters, which in turn will suggest additional experiments for further validating predictions. HeCaToS, organized as a private-public partnership, will generate major socioeconomic impact because it will develop better chemical safety tests leading to safer drugs, but also industrial chemicals, and cosmetics, thereby improving patient and consumer health, and sustaining EU’s industrial competitiveness.

Field of science

  • /medical and health sciences/basic medicine/toxicology
  • /medical and health sciences/basic medicine/physiology

Call for proposal

FP7-HEALTH-2013-INNOVATION-1
See other projects for this call

Funding Scheme

CP-IP - Large-scale integrating project

Coordinator

UNIVERSITEIT MAASTRICHT
Address
Minderbroedersberg 4-6
6200 MD Maastricht
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 673 569
Administrative Contact
René Reijnders (Mr.)

Participants (13)

F. HOFFMANN-LA ROCHE AG
Switzerland
EU contribution
€ 461 500
Address
Grenzacherstrasse 124
4070 Basel
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jason Hannon (Dr.)
INSPHERO AG
Switzerland
EU contribution
€ 262 500
Address
Wagistrasse 27
8952 Schlieren
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jens Kelm (Dr.)
FUNDACION PARA LA INVESTIGACION DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA
Spain
EU contribution
€ 1 113 300
Address
Av Fernando Abril Martorell 106
46026 Valencia
Activity type
Research Organisations
Administrative Contact
Sabrina Femenia (Ms.)
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Switzerland
EU contribution
€ 765 800
Address
Raemistrasse 101
8092 Zuerich
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ralph Schlapbach (Prof.)
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom
EU contribution
€ 1 424 072
Address
South Kensington Campus Exhibition Road
SW7 2AZ London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Tatjana Palalic (Ms.)
LUXCEL BIOSCIENCES LTD
Ireland
EU contribution
€ 524 640
Address
Biotransfer Unit Suite 3-32 Biol
T12 Cork
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Fred Klok (Mr.)
EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany
EU contribution
€ 1 453 040
Address
Meyerhofstrasse 1
69117 Heidelberg
Activity type
Research Organisations
Administrative Contact
Tom Ratcliff (Mr.)
GENEDATA AG
Switzerland
EU contribution
€ 659 432
Address
Margarethenstrasse 38
4053 Basel
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Timo Wittenberger (Dr.)
Klinik Max Planck Institut für Psychiatrie
Germany
EU contribution
€ 650 262
Address
Hofgartenstrasse 8
80539 Muenchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Anke Badrow (Ms.)
KING'S COLLEGE LONDON
United Kingdom
EU contribution
€ 337 500
Address
Strand
WC2R 2LS London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Paul Labbett (Mr.)
RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Germany
EU contribution
€ 694 884
Address
Templergraben 55
52062 Aachen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ernst Schmachtenberg (Prof.)
MicroDiscovery GmbH
Germany
EU contribution
€ 497 500
Address
Marienburger Strasse 1
10405 Berlin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Arif Malik (Dr.)
OPTIBRIUM LIMITED
United Kingdom
EU contribution
€ 482 000
Address
F5-6 Blenheim House Cambridge Innovation Park Denn
CB25 9PB Cambridge
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Matthew Segall (Dr.)