title: Module-based analysis of robustness tradeoffs in the heat shock response system.
abstract: Biological systems have evolved complex regulatory mechanisms, even in situations where much simpler designs seem to be sufficient for generating nominal functionality. Using module-based analysis coupled with rigorous mathematical comparisons, we propose that in analogy to control engineering architectures, the complexity of cellular systems and the presence of hierarchical modular structures can be attributed to the necessity of achieving robustness. We employ the Escherichia coli heat shock response system, a strongly conserved cellular mechanism, as an example to explore the design principles of such modular architectures. In the heat shock response system, the sigma-factor sigma32 is a central regulator that integrates multiple feedforward and feedback modules. Each of these modules provides a different type of robustness with its inherent tradeoffs in terms of transient response and efficiency. We demonstrate how the overall architecture of the system balances such tradeoffs. An extensive mathematical exploration nevertheless points to the existence of an array of alternative strategies for the existing heat shock response that could exhibit similar behavior. We therefore deduce that the evolutionary constraints facing the system might have steered its architecture toward one of many robustly functional solutions.
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka, Japan. kurata@bio.kyutech.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurata
authors.forename: Hana
authors.initials: H
authors.lastname: El-Samad
authors.forename: Rei
authors.initials: R
authors.lastname: Iwasaki
authors.forename: Hisao
authors.initials: H
authors.lastname: Ohtake
authors.forename: John C
authors.initials: JC
authors.lastname: Doyle
authors.forename: Irina
authors.initials: I
authors.lastname: Grigorova
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gross
authors.forename: Mustafa
authors.initials: M
authors.lastname: Khammash
mesh_terms: D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005246:Feedback / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D049490:Systems Biology / Q000379:methods
chemical_list: D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins