Module-based analysis of robustness tradeoffs in the heat shock response system.
Module-based analysis of robustness tradeoffs in the heat shock response system.
复制标题
DOI：
10.1371/journal.pcbi.0020059
复制
发表时间：
2006-07-28
影响因子：
4.3
通讯作者：
Khammash M
中科院分区：
文献类型：
--
作者：
Kurata H;El-Samad H;Iwasaki R;Ohtake H;Doyle JC;Grigorova I;Gross CA;Khammash M
生物系统已经进化出复杂的调节机制，即使在简单得多的设计似乎足以产生名义功能的情况下也是如此。利用基于模块的分析和严格的数学比较，我们提出，与控制工程体系结构类似，蜂窝系统的复杂性和分层模块结构的存在可以归因于实现健壮性的必要性。我们以大肠杆菌热休克反应系统--一种高度保守的细胞机制为例，探索了这种模块化结构的设计原则。在热冲击响应系统中，Sigma因子σ32是一个中央调节器，它集成了多个前馈和反馈模块。这些模块中的每一个都提供了不同类型的稳健性，并在瞬时响应和效率方面进行了固有的权衡。我们将演示系统的整体架构如何平衡这些权衡。然而，一项广泛的数学探索表明，对于现有的热冲击反应，存在一系列替代策略，这些策略可能会表现出类似的行为。因此，我们推断，系统面临的进化约束可能已经将其体系结构引向了许多强大的功能解决方案之一。生物系统在面对环境变化、随机波动和遗传变异引起的各种扰动时保持表型稳定性。这种健壮性似乎是这类系统的固有属性，但在分子水平上仍然知之甚少。同时，在复杂工程系统的研究和设计中取得巨大成功的系统方法为研究细胞机制中健壮性的基本租户提供了独特的机会。这是由于这样一个事实，即在系统层面上，生物学和工程学似乎有大量的共同特征，尽管它们的物理实现非常不同。热休克反应就是这样一个强大的细胞系统，有趣的是，它通过一系列复杂的相互作用实现了看似简单的目标，即折叠或消除热变性蛋白质。与工程控制结构类似，复杂的调节策略似乎是专门设计的解决方案，以针对不同类型的扰动产生鲁棒性。
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. Biological systems maintain phenotypic stability in the face of various perturbations arising from environmental changes, stochastic fluctuations, and genetic variations. This robustness, which seems to be an inherent property of such systems, is still poorly understood at the molecular level. At the same time, systems approaches that were used with great success in the study and design of complex engineered systems provide a unique opportunity for investigating the basic tenants of robustness in cellular mechanisms. This is motivated by the fact that at the system level, biology and engineering seem to have a large number of common features despite their extremely different physical implementations. The heat shock response is one such robust cellular system, which interestingly achieves its seemingly simple objective of refolding or eliminating heat-denatured proteins through a complicated set of interactions. In analogy to engineering control architectures, the complex regulation strategies seem to be a specifically designed solution to generate robustness against different types of perturbations.
登录
查看更多内容
影响因子：
11.4
作者：
Gamer, J;Multhaup, G;Bukau, B
通讯作者：
Bukau, B
影响因子：
10.5
作者：
Guisbert, E;Herman, C;Gross, CA
通讯作者：
Gross, CA
影响因子：
3.2
作者：
Kanemori, M;Nishihara, K;Yura, T
通讯作者：
Yura, T
影响因子：
64.8
作者：
Alon, U;Surette, MG;Leibler, S
通讯作者：
Leibler, S
DOI：
10.1073/pnas.0600828103
发表时间：
2006-04-04
影响因子：
11.1
作者：
Grigorova, IL;Phleger, NJ;Gross, CA
通讯作者：
Gross, CA