Gardner T S, Cantor C R, Collins J J
Department of Biomedical Engineering, Center for BioDynamics, Boston University, Massachusetts 02215, USA.
Nature. 2000 Jan 20;403(6767):339-42. doi: 10.1038/35002131.
It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy.
有人提出，可以用简单调控元件网络构建出具有几乎任何所需特性的基因调控回路。这些特性包括多稳态和振荡，已在诸如噬菌体λ开关和蓝藻生物钟振荡器等特殊基因回路中发现。然而，这些行为尚未在非特殊调控元件网络中得到证实。在此，我们展示了在大肠杆菌中构建一个基因双稳开关——一种合成的双稳态基因调控网络，并提供了一个简单理论，预测双稳态所需的条件。该双稳开关由以相互抑制网络排列的任意两个可阻遏启动子构建而成。通过短暂的化学或热诱导在稳定状态之间切换，且表现出近乎理想的开关阈值。作为一种实用装置，双稳开关形成了一个合成的、可寻址的细胞记忆单元，对生物技术、生物计算和基因治疗具有重要意义。
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