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Section: Partnerships and Cooperations
European Initiatives
ERASysbio+ C5Sys European network.
This European program (http://www.erasysbio.net/index.php?index=272 ) has begun in April 2010, with the title “Circadian and cell cycle clock systems in cancer”. Coordinated by F. Lévi (Villejuif) and D. Rand (Warwick), it studies both from a theoretical and from an experimental viewpoint the relationships between molecular circadian clocks and the cell division cycle, in cancer and in healthy tissues. It has been granted for 3 years. A postdoctoral fellow (F. Billy) works on this subject.
EU-project PASSPORT
Participation in the European network PASSPORT on modelling liver regeneration after partial hepatectomy (http://www.vph-noe.eu/vph-projects/74-eu-fp7-vph-projects/50-passport-strep )
EU-project CANCERSYS
Participation in the European network CANCERSYS on modelling tumour genesis in liver. This project includes also collaborators from the Paris region. A PhD student (William Weens) works on this subject.
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Title: CANCERSYS
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Type: COOPERATION (SANTE)
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Instrument: Specific Targeted Research Project (STREP)
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Duration: November 2008 - October 2011
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Coordinator: Univ. Dortmund (Leibniz Research Centre for Working Environment and Human Factors) (Germany)
EU-project NOTOX
Participation in the European network NOTOX on modelling drug detoxication by liver cells cultivated in bioreactors.
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Title: NOTOX
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Type: COOPERATION (SANTE)
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Instrument: Integrated Project (IP)
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Duration: January 2011 - December 2015
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Coordinator: UNIVERSITAET DES SAARLANDES (Germany)
INRIA Associate Team QUANTISS
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Title: Towards quantitative tissue simulations
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INRIA principal investigator: Dirk Drasdo
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International Partner:
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Duration: 2010 - 2012
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See also: http://www.msysbio.com/ea
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In a recent joint work including members of the BANG and IZBI-teams we were able to predict a novel, so far unrecognized mechanism that is fundamental for a correct regeneration process during liver regeneration by a mathematical hybrid agent-based simulation model (Hoehme et. al., PNAS, 2010) . To identify the model assumptions and the start configuration in the simulation model we combined quantitative information from experimental images on a regenerating liver prior and during regeneration after drug intoxication from animal data with experimental observations of isolated cell-cell-interaction processes from in-vitro (outside the living organism) cell cultures. The model was able to mimic the regeneration process quantitatively. The key mechanism predicted by our mathematical model could subsequently be validated experimentally. It was one of a very few cases in tissue organization where an important mechanism could be correctly predicted by a mathematical model. The modeling work was jointly performed by researchers in INRIA and IZBI. A similar strategy is now performed in other modeling applications to tissue organization included in this collaboration. For this purpose image processing and analysis tools as well as simulation software, developed at IZBI and INRIA, are being extended. The collaboration pursues three major topics (T): T1: Simulation of liver disease and regeneration. This includes liver regeneration after partial hepatectomy (partial removal of liver tissue), steatosis, fibrosis, and liver cancerogenesis (development of liver cancer). Partial hepatectomy is applied after severe lesions, for example caused by liver cancer. Many projects aim at developing multi-scale models including various cell types, spatial tissue architecture, metabolism, cell-cell signaling and signal transduction. The project T1 includes many experimental partners within national and EU projects, most of them in Germany. T2: Simulation of tumor growth and therapy. The role of erythropoietin in Lung cancer therapy should be evaluated and improved therapy schedules should be developed. The model will be multi-level spanning the molecular scale up to the centimeter-scale. This project includes about 15 partner teams in Germany, 11 of them experimental teams and includes the German Cancer Center, a few years ago with a nobel price. T3: Simulation of cell differentiation and lineage specification in multi-cellular aggregates and structured tissues and the role of cell aging. This project addresses the hot topic of stem cell organization in normal and cancer tissues with a special focus on the processes of stem cell transformation and cell re-programming. T4: tumor development and cell aging.
Others
The German part of the BANG project-team and associated team in Leipzig takes part in the Germany-wide Virtual Liver network (VLN) on Systems Biology of the liver (funded by the BMBF) from the molecular level up to the whole organ and body levels. This network is the follow-up of the former Systems Biology network on the “Hepatocyte” through which two PhD students (S. Höhme and A. Krinner) were funded, having recently graduated.
The project includes collaborations within about 10 subprojects with many research groups within Germany (including our main partners from Hepatosys, J.G. Hengstler, Leibniz Research Center, Dortmund, and R. Gebhardt, Univ. of Leipzig).
Key running collaborations exist with the Leibniz Research Center in Dortmund and with the Biochemistry-department of the University of Leipzig on liver regeneration after drug-induced damage and partial hepatectomy. Several other collaborations within the German Consortium on LungCancerSys (BMBF) on the role of Erythropoitin on Lung Cancer must also be mentioned and with the University of Saarbrücken in modelling drug toxicity to hepatocytes in-vitro. Some of the former collaborations are now continued within the different EU projects enumerated above.