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Models of modules: putting the molecular parts together into genetic devices (Meeting rm 2 at the Centre for Mathematical Sciences)

Presented by: 
G Von Dassow [Washington]
Date: 
Tuesday 25th September 2001 - 11:10 to 11:50
Venue: 
No Room Required
Session Title: 
Vertical Integration in Biology: From Molecules to Organisms
Abstract: 
Our research into mathematical models of gene networks began with a curiosity about the genetic architecture of development: to what extent can we say that gene networks are modular building blocks of developmental mechanisms? By "module" we mean a small conspiracy of genes that together exhibit some functional behavior, intrinsic to the network itself and related to the functional role of that network in the organism. I emphasize that modularity is a working assumption, rather than something we are trying to prove rigorously. We've made an extended study of two such putative modules, the Drosophila segment polarity network, and the Drosophila neurogenic network. Our approach has been to do the computer-modeling equivalent of a biochemical reconstitution: add known facts to the model until it begins to exhibit life-like behaviors. The segment polarity module's job is to maintain boundaries; the neurogenic network's job is to mediate lateral inhibition; for both modules, minimal in silico reconstitutions exhibit those behaviors robustly with respect to the kinds of variation that we would expect genetic networks to experience in real life. I'll discuss a handful of results from these models that we find provocative: first, I'll discuss what we've learned about what makes these modules' functional behaviors robust to parameter variation and other insults, and how we think these models shed light on the phenomenon of canalization; next, I'll describe some instances in which the failure of the segment polarity models to account for certain details led us to mechanistic questions about the real network; and finally, I'll talk about some ideas, stimulated by the models, about how these two networks arose, highlighting the hierarchical, nested nature of gene networks.
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