Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA.
Nature. 2010 Jan 21;463(7279):326-30. doi: 10.1038/nature08753.
The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic biology. This focus was elegantly set in motion a decade ago with the design and construction of a genetic toggle switch and an oscillator, with subsequent highlights that have included circuits capable of pattern generation, noise shaping, edge detection and event counting. Here we describe an engineered gene network with global intercellular coupling that is capable of generating synchronized oscillations in a growing population of cells. Using microfluidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring at millimetre scales. We use computational modelling to describe quantitatively the observed dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock sets the stage for the use of microbes in the creation of a macroscopic biosensor with an oscillatory output. Furthermore, it provides a specific model system for the generation of a mechanistic description of emergent coordinated behaviour at the colony level.
在活细胞中具有预测功能的基因电路工程是合成生物学这一不断发展领域的一个明确重点。这一重点在十年前通过设计和构建遗传振子开关和振荡器而被优雅地启动，随后的亮点包括能够产生图案生成、噪声整形、边缘检测和事件计数的电路。在这里，我们描述了一个具有全局细胞间耦合的工程基因网络，该网络能够在不断增长的细胞群体中产生同步振荡。使用针对不同长度尺度的细胞群体定制的微流控设备，我们研究了集体同步特性以及毫米尺度上发生的时空波。我们使用计算建模来定量描述观察到的整体振荡的周期和幅度对流速的依赖性。同步遗传时钟为在创建具有振荡输出的宏观生物传感器中使用微生物奠定了基础。此外，它为在群体水平上产生对新兴协调行为的机制描述提供了一个特定的模型系统。
