Toward Systems Biology

May 30 - 31, June 1, 2011


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Towards Multi-cellular Systems Biology: Liver Regeneration and Cancerogenesis

The main benefit of systems biology approaches is using the synergies of experiments and mathematical models to answer biological questions. So far the main focus of current systems biology is on intracellular processes. The recent progress was largely triggered by advances in experimental techniques permitting to validate important aspects of the mathematical models.

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 permit systems biology approaches in the histological lengths scale. To illustrate our method we reconstructed and modeled regeneration after toxic liver damage and after partial hepatectomy, and outline recent results on cancerogenesis in liver.

We have chosen the example of the regenerating liver, because 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. 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 could subsequently be experimentally confirmed. For liver regeneration after partial hepatectomy in mice, our model predicts that only if cell proliferation is distributed uniformly over the liver lobule, liver mass can be recovered within the experimentally observed time period. Our model for liver cancerogenesis give possible explanations of the two observed phenotypes: a well and a poorly differentiated one. We believe our procedure is widely applicable for tissues.

Dirk Drasdo, INRIA Paris-Rocqencour