Systemsvergnügen: model-guided empiricism

4 June 2010

Peter Sorger
Department of Systems Biology
Harvard Medical School


I will discuss our recent attempts to measure, model and manipulate variability in the responses of mammalian cells to extracellular stimuli and small molecule drugs. Our examination of signal transduction in genetically homogeneous populations of cells responding to natural ligands and drugs reveals remarkable variability in most responses but near constancy in few. From one perspective, variability might be a rather uninteresting consequence of stochastic biochemical reactions. However, cell-to-cell variability might actually be adaptive, conferring on ensembles of cells properties that would not be observed were all responses the same. The ubiquity of variation also calls into question recent theories about "cancer stem cells", many of whose properties are more easily explained by random variation than the presence of special populations of pluripotent cancer progenitors. I will discuss these ideas as an example of Systemsvergnügen (!) in which rather simple mathematic models provide a satisfying theory that has thus far eluded conventional molecular analysis.

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