130 research outputs found
Inferring Biological Mechanisms by Data-Based Mathematical Modelling: Compartment-Specific Gene Activation during Sporulation in Bacillus subtilis as a Test Case
Biological functionality arises from the complex interactions of simple components. Emerging behaviour is difficult to recognize with verbal models alone, and mathematical approaches are important. Even few interacting components can give rise to a wide range of different responses, that is, sustained, transient, oscillatory, switch-like responses, depending on the values of the model parameters. A quantitative comparison of model predictions and experiments is therefore important to distinguish between competing hypotheses and to judge whether a certain regulatory behaviour is at all possible and plausible given the observed type and strengths of interactions and the speed of reactions. Here I will review a detailed model for the transcription factor ĻF, a regulator of cell differentiation during sporulation in Bacillus subtilis. I will focus in particular on the type of conclusions that can be drawn from detailed, carefully validated models of biological signaling networks. For most systems, such detailed experimental information is currently not available, but accumulating biochemical data through technical advances are likely to enable the detailed modelling of an increasing number of pathways. A major challenge will be the linking of such detailed models and their integration into a multiscale framework to enable their analysis in a larger biological context
Simulations demonstrate a simple network to be sufficient to control branch point selection, smooth muscle and vasculature formation during lung branching morphogenesis
Proper lung functioning requires not only a correct structure of the
conducting airway tree, but also the simultaneous development of smooth muscles
and vasculature. Lung branching morphogenesis is strongly stereotyped and
involves the recursive use of only three modes of branching. We have previously
shown that the experimentally described interactions between Fibroblast growth
factor (FGF)10, Sonic hedgehog (SHH) and Patched (Ptc) can give rise to a
Turing mechanism that not only reproduces the experimentally observed wildtype
branching pattern but also, in part counterintuitive, patterns in mutant mice.
Here we show that, even though many proteins affect smooth muscle formation and
the expression of Vegfa, an inducer of blood vessel formation, it is sufficient
to add FGF9 to the FGF10/SHH/Ptc module to successfully predict simultaneously
the emergence of smooth muscles in the clefts between growing lung buds, and
Vegfa expression in the distal sub-epithelial mesenchyme. Our model reproduces
the phenotype of both wildtype and relevant mutant mice, as well as the results
of most culture conditions described in the literature.Comment: Initially published at Biology Ope
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