Department of Biosciences, Rice University, Houston, TX, USA.
Department of Mathematics, University of Houston, Houston, TX, USA.
Nat Commun. 2020 Jul 21;11(1):3659. doi: 10.1038/s41467-020-17475-z.
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.
随着合成生物电路变得越来越复杂，在多菌株微生物群落中分配计算变得越来越有益。然而，设计能够对群落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，我们开发了一种两菌株基因电路，该电路能够感知并响应哪种菌株占优势。这涉及到一个共抑制系统，其中每个菌株产生一种信号分子，向另一个菌株发出信号，使其下调自身正交信号分子的产生。这种共抑制群落将基因表达与菌株的比例而不是种群大小联系起来。此外，我们通过外部诱导来控制优势的交叉点。我们通过开发一个数学模型来阐明这些动态的机制，该模型可以根据菌株分数和外部诱导的变化来捕捉群落的反应。这些结果表明，简单的基因电路可以在多细胞合成系统中用于感知和响应种群的状态。
