CANCERSYS

"Mathematical modelling of beta-catenin and ras signalling in liver and its impact on proliferation, tissue organization and formation of hepatocellular carcinomas"

 Coordinatore FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ E.V. 

 Organization address address: ARDEYSTRASSE 67
city: DORTMUND
postcode: 44139

contact info
Titolo: Mr.
Nome: Michael
Cognome: Paul
Email: send email
Telefono: +49 231 1084204
Fax: +49 231 1084326

 Nazionalità Coordinatore Germany [DE]
 Totale costo 3˙989˙366 €
 EC contributo 2˙992˙024 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2007-B
 Funding Scheme CP-FP
 Anno di inizio 2008
 Periodo (anno-mese-giorno) 2008-11-01   -   2011-10-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ E.V.

 Organization address address: ARDEYSTRASSE 67
city: DORTMUND
postcode: 44139

contact info
Titolo: Mr.
Nome: Michael
Cognome: Paul
Email: send email
Telefono: +49 231 1084204
Fax: +49 231 1084326

DE (DORTMUND) coordinator 0.00
2    ALBERT-LUDWIGS-UNIVERSITAET FREIBURG

 Organization address address: FAHNENBERGPLATZ
city: FREIBURG
postcode: 79085

contact info
Titolo: Prof.
Nome: Jens
Cognome: Timmer
Email: send email
Telefono: +49 761 203 5829
Fax: +49 761 203 5967

DE (FREIBURG) participant 0.00
3    CHARITE - UNIVERSITAETSMEDIZIN BERLIN

 Organization address address: Chariteplatz 1
city: BERLIN
postcode: 10117

contact info
Titolo: Ms.
Nome: Eveline
Cognome: Fraessdorf
Email: send email
Telefono: +49 30 450576024
Fax: +49 30 450576954

DE (BERLIN) participant 0.00
4    DEUTSCHES KREBSFORSCHUNGSZENTRUM

 Organization address address: Im Neuenheimer Feld 280
city: HEIDELBERG
postcode: 69120

contact info
Titolo: Ms.
Nome: Bettina
Cognome: Crispin
Email: send email
Telefono: +49 6221 422700
Fax: +49 6221 422708

DE (HEIDELBERG) participant 0.00
5    EBERHARD KARLS UNIVERSITAET TUEBINGEN

 Organization address address: GESCHWISTER-SCHOLL-PLATZ
city: TUEBINGEN
postcode: 72074

contact info
Titolo: Prof.
Nome: Michael
Cognome: Schwarz
Email: send email
Telefono: +49 7071 29 77398
Fax: +49 7071 29 2273

DE (TUEBINGEN) participant 0.00
6    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

 Organization address address: 101 Rue de Tolbiac
city: PARIS
postcode: 75654

contact info
Titolo: Ms.
Nome: Annick
Cognome: Bertault
Email: send email
Telefono: +33 1 40784901
Fax: +33 1 40781998

FR (PARIS) participant 0.00
7    INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET EN AUTOMATIQUE

 Organization address address: Domaine de Voluceau, Rocquencourt
city: LE CHESNAY Cedex
postcode: 78153

contact info
Titolo: Ms.
Nome: Sandrine
Cognome: Lassout
Email: send email
Telefono: +33 1 3963 5390
Fax: +33 1 39 63 50 34

FR (LE CHESNAY Cedex) participant 0.00
8    STIFTELSEN FRAUNHOFER-CHALMERS CENTRUM FOR INDUSTRIMATEMATIK

 Organization address address: Chalmers Science Park
city: GOETEBORG
postcode: 41288

contact info
Titolo: Dr.
Nome: Mats
Cognome: Jirstrand
Email: send email
Telefono: +46 31 7724250
Fax: +46 31 7724260

SE (GOETEBORG) participant 0.00
9    UNIVERSITAET LEIPZIG

 Organization address address: RITTERSTRASSE 26
city: LEIPZIG
postcode: 4109

contact info
Titolo: Prof.
Nome: Rolf
Cognome: Gebhardt
Email: send email
Telefono: +49 341 97 22 100
Fax: +49 341 97 22109

DE (LEIPZIG) participant 0.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

single    pathways    hepatocellular    proliferation    dynamic    predictions    signalling    carcinoma    ras    liver    mouse    therapeutic    organ    predict    cell    organization    cells    interactions    intervention    members    spatial    temporal    inducible    expression    carcinogenesis    structure    microarchitecture    cancer    scientists    catenin    related    strategies    dimensional    impact    networks    combined    beta    model    hepatocytes    cancersys    activation    lobule    induction    rate    validated    tissue    influence   

 Obiettivo del progetto (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.'

Introduzione (Teaser)

Carcinogenesis is a complex process involving activation or silencing of various signalling pathways. A European consortium decided to model the combined influence of two cancer-related pathways in the development of liver cancer.

Descrizione progetto (Article)

The liver is a vital organ of multiple functions, including protein synthesis, detoxification and production of digestive enzymes. Understanding how cells establish the structure of the liver and how they behave during regeneration or cancer formation is poorly understood.

To contribute to knowledge in this area, the EU-funded Cancersys project focused on developing a model of liver architecture and hepatocellular carcinoma. Firstly, project members established a procedure for tissue spatial-temporal modelling based on confocal laser scans, image processing and three-dimensional tissue reconstruction. This technique was applied to understand liver microarchitecture during cancer formation.

The Cancersys model captured liver lobule structure, focusing on veins, and normal and malignant cell types. It facilitated the analysis of various parameters such as cell proliferation status and rate, cell death rate and three-dimensional cell orientation during tumour formation.

In a second step, the beta catenin and ras signalling pathways were integrated in the model. The aim was to predict the impact of the activation of these cancer-related pathways on single cell decision and tissue organisation.

By coupling the modelling approach with whole genome expression profiling from hepatocytes with activated beta-catenin or ras signalling, scientists identified negative interactions between both pathways. Signalling through beta-catenin led to attenuation of expression of genes that are positively regulated by the ras signalling module and vice versa. Project scientists planned to test candidate molecules responsible for this interaction in transgenic mice of inducible beta-catenin and ras signalling.

The Cancersys model offered a predictive approach for determining the role of cancer-related signalling cascades in hepatocellular carcinoma. Partners are hopeful that their model will lead to the design of effective intervention and therapeutic strategies against cancer.

Altri progetti dello stesso programma (FP7-HEALTH)

EU-GEI (2010)

European Network of National Schizophrenia Networks Studying Gene-Environment Interactions

Read More  

SYSTEMTB (2010)

Systems biology of Mycobacterium tuberculosis

Read More  

EXALT (2014)

"Proposal to assess an innovative Immunotherapy, based on a thioredox peptide antigen, in a Phase I Trial for Type-1 Diabetes"

Read More