A novel optogenetically tunable frequency modulating oscillator.
A novel optogenetically tunable frequency modulating oscillator.
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DOI：
10.1371/journal.pone.0183242
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Rai K
中科院分区：
文献类型：
--
作者：
Mahajan T;Rai K
合成生物学使得生物可重构电路的创建成为可能，该电路执行垄断单个生物机器的多种功能;这样的系统可以响应环境线索在不同行为之间切换。以前的工作已经证明了可切换的动态行为，采用可重构逻辑门遗传网络。在这里，我们描述了一个计算框架的可重构电路在大肠杆菌使用逻辑门的组合，并提出了生物实现。所提出的系统是一个振荡器，可以表现出的频率和振幅的振荡的可调谐性。此外，可以光遗传学地改变操作频率。Insilico分析表明，双组分光系统响应于某一频率范围内的光，可用于调制振荡器的频率或完全停止振荡。计算模型表明，混合以不同频率振荡的两个大肠杆菌菌落会产生空间节拍模式。此外，我们表明，这些振荡更鲁棒地响应输入扰动相比，基础振荡器，建议的振荡器是一个修改。与基本振荡器相比，所提出的系统在参数空间的较大区域中在细胞群体中显示出更快的同步。此外，该振荡器在输入扰动后的过渡期内还表现出较小的同步误差。这为在细菌和其他生物体中构建合成可重构电路提供了强有力的基础，其可以按比例放大以在具有可调剂量的时间依赖性药物递送领域中执行功能，并为进一步开发具有同步群体水平行为的电路奠定了基础。
Synthetic biology has enabled the creation of biological reconfigurable circuits, which perform multiple functions monopolizing a single biological machine; Such a system can switch between different behaviours in response to environmental cues. Previous work has demonstrated switchable dynamical behaviour employing reconfigurable logic gate genetic networks. Here we describe a computational framework for reconfigurable circuits in E.coli using combinations of logic gates, and also propose the biological implementation. The proposed system is an oscillator that can exhibit tunability of frequency and amplitude of oscillations. Further, the frequency of operation can be changed optogenetically. Insilico analysis revealed that two-component light systems, in response to light within a frequency range, can be used for modulating the frequency of the oscillator or stopping the oscillations altogether. Computational modelling reveals that mixing two colonies of E.coli oscillating at different frequencies generates spatial beat patterns. Further, we show that these oscillations more robustly respond to input perturbations compared to the base oscillator, to which the proposed oscillator is a modification. Compared to the base oscillator, the proposed system shows faster synchronization in a colony of cells for a larger region of the parameter space. Additionally, the proposed oscillator also exhibits lesser synchronization error in the transient period after input perturbations. This provides a strong basis for the construction of synthetic reconfigurable circuits in bacteria and other organisms, which can be scaled up to perform functions in the field of time dependent drug delivery with tunable dosages, and sets the stage for further development of circuits with synchronized population level behaviour.
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影响因子：
3.7
作者：
Gonze D;Abou-Jaoudé W
通讯作者：
Abou-Jaoudé W
影响因子：
3.7
作者：
Hillenbrand P;Fritz G;Gerland U
通讯作者：
Gerland U
DOI：
10.1093/bioinformatics/btp310
发表时间：
2009-07-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Chen BS;Chang CH;Lee HC
通讯作者：
Lee HC
影响因子：
17.1
作者：
Courbet, Alexis;Endy, Drew;Bonnet, Jerome
通讯作者：
Bonnet, Jerome
影响因子：
2.7
作者：
Engelborghs, K;Luzyanina, T;Roose, D
通讯作者：
Roose, D