Module-based analysis of robustness tradeoffs in the heat shock response system.

Full 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.

Author information

Author/s: Kurata, Hiroyuki (H); El-Samad, Hana (H); Iwasaki, Rei (R); Ohtake, Hisao (H); Doyle, John C (JC); Grigorova, Irina (I); Gross, Carol A (CA); Khammash, Mustafa (M);

Affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka, Japan. kurata(-atsign-)bio.kyutech.ac.jp

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: PLoS computational biology (PLoS Comput Biol), published in United States. (Language: eng)

Reference: 2006-Jul; vol 2 (issue 7) : pp e59

Dates: Created 2006/07/25; Completed 2006/09/05; Revised 2008/11/20;

PMID: 16863396, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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