Majority sensing in synthetic microbial consortia
Majority sensing in synthetic microbial consortia
复制标题
DOI：
10.1038/s41467-020-17475-z
复制
发表时间：
2020-07-21
影响因子：
16.6
通讯作者：
Bennett, Matthew R.
中科院分区：
文献类型：
--
作者：
Alnahhas, Razan N.;Sadeghpour, Mehdi;Bennett, Matthew R.
随着合成生物电路变得越来越复杂，在多菌株微生物联盟内分散计算变得越来越有利。然而，设计能够对联合体组成的变化做出可预测响应的分布式电路仍然是一个挑战。在这里，我们开发了一个两种菌株的基因电路，它可以感知和响应哪种菌株占多数。这涉及到一个共抑制系统，在这个系统中，每个菌株产生一个信号分子，该分子向另一个菌株发出信号，以下调自己的正交信号分子的产生。这个共抑制联盟将基因表达与菌株的比例联系起来，而不是种群大小。此外，我们通过外部诱导来控制多数的交叉点。我们通过建立一个数学模型来解释驱动这些动力学的机制，该模型捕获了当应变分数和外部诱导不同时的联合体响应。这些结果表明，在多细胞合成系统中，可以使用简单的基因电路来感知和响应种群的状态。
As synthetic biocircuits become more complex, distributing computations within multi-strain microbial consortia becomes increasingly beneficial. However, designing distributed circuits that respond predictably to variation in consortium composition remains a challenge. Here we develop a two-strain gene circuit that senses and responds to which strain is in the majority. This involves a co-repressive system in which each strain produces a signaling molecule that signals the other strain to down-regulate production of its own, orthogonal signaling molecule. This co-repressive consortium links gene expression to ratio of the strains rather than population size. Further, we control the cross-over point for majority via external induction. We elucidate the mechanisms driving these dynamics by developing a mathematical model that captures consortia response as strain fractions and external induction are varied. These results show that simple gene circuits can be used within multicellular synthetic systems to sense and respond to the state of the population.