美国加州大学圣地亚哥分校Jeff Hasty小组的一项最新研究利用剪刀-石头-布的原理开发出工程化种群动态性,从而能够增加遗传稳定性。相关论文发表在2019年9月6日出版的《科学》上。
研究人员采用以生态相互作用为指导的互补方法,通过这种方法设计循环群体控制以稳定细胞内基因回路的功能。研究人员设计了三种大肠杆菌菌株,使得每种菌株可以杀死或者被另外两种菌株中的一种杀死。由此得到的“剪刀-石头-布”动态体现了微流控装置中菌株的快速循环,并使得细胞培养中基因回路功能的稳定性增加。
研究人员表示,合成生物学的进步已经产生了一系列原理验证型细菌回路,可用于从治疗到生物生产的各种应用。对于大多数应用来说,一个相同的挑战是选择性压力的存在,这导致工程菌的突变率增加。一种常见的策略是开发克隆技术,旨在增加单细胞中有害突变的固定时间。
附:英文原文
Title: Rock-paper-scissors: Engineered population dynamics increase genetic stability
Author: Michael J. Liao, M. Omar Din, Lev Tsimring, Jeff Hasty
Issue&Volume: Volume 365 Issue 6457
Abstract: Advances in synthetic biology have led to an arsenal of proof-of-principle bacterial circuits that can be leveraged for applications ranging from therapeutics to bioproduction. A unifying challenge for most applications is the presence of selective pressures that lead to high mutation rates for engineered bacteria. A common strategy is to develop cloning technologies aimed at increasing the fixation time for deleterious mutations in single cells. We adopt a complementary approach that is guided by ecological interactions, whereby cyclical population control is engineered to stabilize the functionality of intracellular gene circuits. Three strains of Escherichia coli were designed such that each strain could kill or be killed by one of the other two strains. The resulting “rock-paper-scissors” dynamic demonstrates rapid cycling of strains in microfluidic devices and leads to an increase in the stability of gene circuit functionality in cell culture.
DOI: 10.1126/science.aaw0542
Source:https://science.sciencemag.org/content/365/6457/1045