Elowitz M B, Leibler S
Department of Molecular Biology and Physics, Princeton University, New Jersey 08544, USA.
Nature. 2000 Jan 20;403(6767):335-8. doi: 10.1038/35002125.
Networks of interacting biomolecules carry out many essential functions in living cells, but the 'design principles' underlying the functioning of such intracellular networks remain poorly understood, despite intensive efforts including quantitative analysis of relatively simple systems. Here we present a complementary approach to this problem: the design and construction of a synthetic network to implement a particular function. We used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli. The network periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells. The resulting oscillations, with typical periods of hours, are slower than the cell-division cycle, so the state of the oscillator has to be transmitted from generation to generation. This artificial clock displays noisy behaviour, possibly because of stochastic fluctuations of its components. Such 'rational network design may lead both to the engineering of new cellular behaviours and to an improved understanding of naturally occurring networks.
相互作用的生物分子网络在活细胞中执行许多基本功能，然而，尽管人们进行了大量努力，包括对相对简单系统的定量分析，但此类细胞内网络运作背后的“设计原则”仍知之甚少。在此，我们提出一种解决该问题的补充方法：设计并构建一个执行特定功能的合成网络。我们利用三个并非任何自然生物钟组成部分的转录抑制系统，在大肠杆菌中构建了一个振荡网络，称为抑制器。该网络周期性地诱导绿色荧光蛋白的合成，以此作为其在单个细胞中状态的读出信号。产生的振荡周期通常为数小时，比细胞分裂周期慢，因此振荡器的状态必须代代相传。这个人工时钟表现出噪声行为，可能是由于其组件的随机波动所致。这种“合理的网络设计”可能既会带来新细胞行为的工程设计，也会增进对自然存在网络的理解。
