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Controlling spatiotemporal pattern formation in a concentration gradient with a synthetic toggle switch.
Molecular Systems Biology ( IF 8.5 ) Pub Date : 2020-06-12 , DOI: 10.15252/msb.20199361
Içvara Barbier 1 , Rubén Perez-Carrasco 2, 3 , Yolanda Schaerli 1
Affiliation  

The formation of spatiotemporal patterns of gene expression is frequently guided by gradients of diffusible signaling molecules. The toggle switch subnetwork, composed of two cross‐repressing transcription factors, is a common component of gene regulatory networks in charge of patterning, converting the continuous information provided by the gradient into discrete abutting stripes of gene expression. We present a synthetic biology framework to understand and characterize the spatiotemporal patterning properties of the toggle switch. To this end, we built a synthetic toggle switch controllable by diffusible molecules in Escherichia coli . We analyzed the patterning capabilities of the circuit by combining quantitative measurements with a mathematical reconstruction of the underlying dynamical system. The toggle switch can produce robust patterns with sharp boundaries, governed by bistability and hysteresis. We further demonstrate how the hysteresis, position, timing, and precision of the boundary can be controlled, highlighting the dynamical flexibility of the circuit.

中文翻译:

使用合成拨动开关控制浓度梯度中的时空图案形成。

基因表达时空模式的形成通常由可扩散信号分子的梯度引导。切换开关子网络由两个交叉抑制转录因子组成,是负责模式化的基因调控网络的常见组件,将梯度提供的连续信息转换为离散的相邻基因表达条纹。我们提出了一个合成生物学框架来理解和表征切换开关的时空图案特性。为此,我们构建了一种可由大肠杆菌中的扩散分子控制的合成拨动开关。我们通过将定量测量与底层动态系统的数学重建相结合来分析电路的图案化能力。拨动开关可以产生具有清晰边界的鲁棒图案,由双稳态和迟滞控制。我们进一步演示了如何控制边界的迟滞、位置、定时和精度,突出了电​​路的动态灵活性。
更新日期:2020-06-30
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