Toward Systems Biology
May 30 - 31, June 1, 2011
Grenoble
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