Objective The goal of the CANCERSYS project is to establish a multi-scale model for two major signalling pathways involved in the formation of hepatocellular carcinoma, the beta-catenin and ras signalling pathways. Integrative studies linking measurements in primary heptocytes with effects at the organ level will address the impact of these signalling networks on proliferation, tissue organization and formation of hepatocellular carcinoma. In a close collaboration of scientists from theoretical fields and life sciences, our approach will combine dynamic modelling of signalling networks with spatial-temporal modelling of the liver microarchitecture. For this purpose dynamic models of the beta-catenin and ras core modules and their interactions will be integrated into a single-cell based three-dimensional model of the liver lobule. This model will be used to predict the impact of beta-catenin and ras activation on tissue organization starting with the early events, such as enhanced proliferation as well as micromotility of single cells, followed by formation of nodules and finally of dedifferentiated hepatocarcinomas. Predictions obtained by the model will be validated by inducible Apclox/lox and Ha-rasQ61R mouse strains, which have already been established by members of our consortium and allow induction of hepatocellular carcinoma. In addition the model predictions of the combined influence of active beta-catenin and ras signalling will be validated using a mouse strain that allows induction of both pathways in hepatocytes. In an iterative process, the model will be validated and adjusted to the in vivo situation. The model aims at the identification of systems properties of beta-catenin and ras signalling exploited during carcinogenesis and will foster the prediction of strategies for effective intervention, thereby facilitating the design of novel therapeutic strategies to combat hepatocellular carcinoma. Fields of science natural sciencesmathematicsapplied mathematicsmathematical model Keywords beta-catenin hepatocellular cancer liver microarchitecture multi-scale model primary hepatocytes signal transduction networks spatial-temporal modelling Programme(s) FP7-HEALTH - Specific Programme "Cooperation": Health Topic(s) HEALTH-2007-2.1.2-5 - Multidisciplinary fundamental genomics and molecular biology approaches to study basic biological processes relevant to health and diseases Call for proposal FP7-HEALTH-2007-B See other projects for this call Funding Scheme CP-FP - Small or medium-scale focused research project Coordinator FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ EV EU contribution € 854 850,00 Address ARDEYSTRASSE 67 44139 Dortmund Germany See on map Region Nordrhein-Westfalen Arnsberg Dortmund, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Michael Paul (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (8) Sort alphabetically Sort by EU Contribution Expand all Collapse all ALBERT-LUDWIGS-UNIVERSITAET FREIBURG Germany EU contribution € 250 800,00 Address FAHNENBERGPLATZ 79098 Freiburg See on map Region Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Jens Timmer (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET AUTOMATIQUE France EU contribution € 273 300,00 Address DOMAINE DE VOLUCEAU ROCQUENCOURT 78153 Le Chesnay Cedex See on map Region Ile-de-France Ile-de-France Yvelines Activity type Research Organisations Administrative Contact Sandrine Lassout (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Germany EU contribution € 280 800,00 Address IM NEUENHEIMER FELD 280 69120 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Administrative Contact Bettina Crispin (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France EU contribution € 280 800,00 Address RUE DE TOLBIAC 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Annick Bertault (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data EBERHARD KARLS UNIVERSITAET TUEBINGEN Germany EU contribution € 280 800,00 Address GESCHWISTER-SCHOLL-PLATZ 72074 Tuebingen See on map Region Baden-Württemberg Tübingen Tübingen, Landkreis Activity type Higher or Secondary Education Establishments Administrative Contact Michael Schwarz (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSITAET LEIPZIG Germany EU contribution € 280 800,00 Address RITTERSTRASSE 26 04109 Leipzig See on map Region Sachsen Leipzig Leipzig Activity type Higher or Secondary Education Establishments Administrative Contact Rolf Gebhardt (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data STIFTELSEN FRAUNHOFER-CHALMERS CENTRUM FOR INDUSTRIMATEMATIK Sweden EU contribution € 250 800,00 Address CHALMERS TEKNIKPARK 41288 GOETEBORG See on map Region Södra Sverige Västsverige Västra Götalands län Activity type Research Organisations Administrative Contact Mats Jirstrand (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data CHARITE - UNIVERSITAETSMEDIZIN BERLIN Germany EU contribution € 239 074,00 Address Chariteplatz 1 10117 Berlin See on map Region Berlin Berlin Berlin Activity type Higher or Secondary Education Establishments Administrative Contact Eveline Fraessdorf (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data