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Module-Based Analysis of Robustness Tradeoffs in the Heat Shock Response System

Kurata, Hiroyuki and El-Samad, Hana and Iwasaki, Rei and Ohtake, Hisao and Doyle, John C. and Grigorova, Irina and Gross, Carol A. and Khammash, Mustafa (2006) Module-Based Analysis of Robustness Tradeoffs in the Heat Shock Response System. PLOS Computational Biology, 2 (7). pp. 663-675. ISSN 1553-7358. PMCID PMC1523291. doi:10.1371/journal.pcbi.0020059.

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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 σ32 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.

Item Type:Article
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URLURL TypeDescription CentralArticle
El-Samad, Hana0000-0001-6239-9916
Doyle, John C.0000-0002-1828-2486
Additional Information:Copyright: © 2006 Kurata et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: September 29, 2005; Accepted: April 13, 2006; Published: July 28, 2006 HK, HES, HO, JCD, CAG, and MK conceived and designed the experiments. HK and RI performed the experiments. HK, HES, and CAG analyzed the data. HES, JCD, IG, CAG, and MK contributed reagents/materials/analysis tools. HK, HES, JCD, CAG, and MK wrote the paper. Competing interests. The authors have declared that no competing interests exist. This material is based upon work supported by National Science Foundation grant CCF-0326576, Institute of Collaborative Biotechnologies grant DAAD19-03-D-0004 from the US Army Research office, the Rice Genome Simulator Project of the National Institute of Agrobiological Sciences, and the Sandler Family Supporting Foundation.
Issue or Number:7
PubMed Central ID:PMC1523291
Record Number:CaltechAUTHORS:KURploscompbio06
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Official Citation:Kurata H, El-Samad H, Iwasaki R, Ohtake H, Doyle JC, et al. (2006) Module-based analysis of robustness tradeoffs in the heat shock response system. PLoS Comput Biol 2(7): e59. DOI: 10.1371/journal.pcbi.0020059
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:4395
Deposited By: Archive Administrator
Deposited On:21 Aug 2006
Last Modified:08 Nov 2021 20:17

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