Abstract

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. 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, will be used and 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) and liver cancerogenesis (development of liver cancer). Partial hepatectomy is applied after severe lesions, for example caused by liver cancer. 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, last year awarded with a nobel price. T3: Simulation of cell differentiation and lineage specification in multi-cellular aggregates and structured tissues. 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.