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The 2nd Biosupercomputing Symposium

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Towards the Systems Biology of Tissues: Predicting liver regeneration and tumor growth

Dr. Dirk Drasdo
Directeur de Recherche, INRIA

Systems biology is currently extending towards the spatial scale of cells, cell assemblies and whole tissues. This talk will survey individual (agent) based models of multi-cellular tissues and consider as a state-of-art example the quantitative modeling of liver regeneration after drug damage. In this example it will be explored how cells coordinately behave to establish functional tissue structure and to restore micro-architecture during regeneration. Research in this field suffers from a lack of techniques that permits quantification of tissue architecture and its development. To bridge this gap we have established a procedure based on confocal laser scans, image processing and three-dimensional tissue reconstruction, as well as on quantitative mathematical modeling. To illustrate our method, that we believe is applicable to many tissues, we reconstructed and modeled regeneration after toxic liver damage.
We have chosen the example of the regenerating liver, because here function and architecture are tightly linked: liver function depends on the complex micro-architecture formed by hepatocytes and micro-vessels (sinusoids) that ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures the whole regeneration process. Hepatocytes are modeled as individual agents parameterized by measurable biophysical and cell-biological quantities. The model unambiguously predicted a so far unrecognized mechanism, the alignment of daughter hepatocytes along the closest sinusoids as essential for liver regeneration that was subsequently experimentally validated. Finally we will give an overview over multi-scale and hybrid modeling in tumor growth centered about individual-based models as that used to mimic liver regeneration.

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