Damped oscillations in the adaptive response of the iron homeostasis network of E-coli
Damped oscillations in the adaptive response of the iron homeostasis network of E-coli
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DOI：
10.1111/j.1365-2958.2010.07111.x
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发表时间：
2010-04-01
影响因子：
3.6
通讯作者：
Stavans, Joel
中科院分区：
文献类型：
--
作者：
Amir, Amnon;Meshner, Shiri;Stavans, Joel
生物体常常要适应环境的突然变化，达到体内平衡.为了实现适应，细胞在其遗传网络中部署反馈等基序，赋予细胞反应所需的特性。研究了E.大肠杆菌，它采用反馈回路来调节铁的使用和吸收，同时保持细胞内铁在无毒水平。利用荧光报告的铁依赖性启动子在散装和微流体为基础的，单细胞实验，我们表明，E。大肠杆菌细胞表现出阻尼振荡的基因表达，突然减少外部铁水平。振荡，持续几代，是独立的位置沿着细胞周期。在网络组件中的突变体的实验表明参与铁的吸收的振荡。我们的研究结果表明，该反应是由细胞内铁振荡驱动的，足以诱导几乎完全的网络激活/失活。我们提出了一个数学模型的基础上关闭的快速铁吸收的负反馈回路，并包括铁的使用和存储，它捕捉到的主要特征观察到的行为。总而言之，我们的结果揭示了细菌铁代谢的控制，并表明振荡代表了稳定性要求和响应速度之间的妥协。
P>Living organisms often have to adapt to sudden environmental changes and reach homeostasis. To achieve adaptation, cells deploy motifs such as feedback in their genetic networks, endowing the cellular response with desirable properties. We studied the iron homeostasis network of E. coli, which employs feedback loops to regulate iron usage and uptake, while maintaining intracellular iron at non-toxic levels. Using fluorescence reporters for iron-dependent promoters in bulk and microfluidics-based, single-cell experiments, we show that E. coli cells exhibit damped oscillations in gene expression, following sudden reductions in external iron levels. The oscillations, lasting for several generations, are independent of position along the cell cycle. Experiments with mutants in network components demonstrate the involvement of iron uptake in the oscillations. Our findings suggest that the response is driven by intracellular iron oscillations large enough to induce nearly full network activation/deactivation. We propose a mathematical model based on a negative feedback loop closed by rapid iron uptake, and including iron usage and storage, which captures the main features of the observed behaviour. Taken together, our results shed light on the control of iron metabolism in bacteria and suggest that the oscillations represent a compromise between the requirements of stability and speed of response.