Løvdok Linda, Kollmann Markus, Sourjik Victor
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
J Biotechnol. 2007 Apr 30;129(2):173-80. doi: 10.1016/j.jbiotec.2007.01.024. Epub 2007 Feb 8.
Biological systems are exposed to various perturbations that affect performance of the cellular networks, with stochastic variation in protein levels, or gene expression noise, being one of the major sources of intracellular perturbations. We recently used Escherichia coli chemotaxis as a model to analyze robustness against such noise and demonstrated theoretically and experimentally that a steady-state output of the pathway is robust against concerted variation in the levels of all chemotaxis proteins. However, our model predicted that the pathway topology does not confer much robustness against an uncorrelated variation in the protein levels. To test whether additional robustness features might be missing from our model, we compare here its predictions with an experimentally determined chemotactic performance under varying levels of individual proteins. Our data show that the pathway is indeed even more robust than predicted to two types of perturbations-the variation in the levels of the adaptation enzymes and a correlated expression of CheY and CheZ. Although the design features that are responsible for this higher robustness still remain to be understood, our results stress the importance of a robust design of both native and synthetic signaling networks.
生物系统会受到各种影响细胞网络性能的干扰,蛋白质水平的随机变化,即基因表达噪声,是细胞内干扰的主要来源之一。我们最近以大肠杆菌趋化作用为模型来分析针对此类噪声的稳健性,并通过理论和实验证明该信号通路的稳态输出对于所有趋化蛋白水平的协同变化具有稳健性。然而,我们的模型预测该信号通路拓扑结构对于蛋白质水平的不相关变化并没有赋予太多稳健性。为了测试我们的模型是否遗漏了其他稳健性特征,我们在此将其预测结果与在不同单个蛋白质水平下通过实验确定的趋化性能进行比较。我们的数据表明,该信号通路对于两种类型的干扰——适应酶水平的变化以及CheY和CheZ的相关表达——实际上比预测的更加稳健。尽管导致这种更高稳健性的设计特征仍有待了解,但我们的结果强调了天然和合成信号网络稳健设计的重要性。