Abstract
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.
Highlights
As synthetic biocircuits become more complex, distributing computations within multi-strain microbial consortia becomes increasingly beneficial
The traditional function of quorum sensing (QS) in bacteria is to activate gene expression based on overall population size[22]
CinI Plac lacI-11 Prhl sfYFP Plac by upregulating the gene encoding a dimeric version of LacI (LacI-11)[31], which downregulates the genes encoding the super folder variant of yellow fluorescent protein and CinI34
Summary
As synthetic biocircuits become more complex, distributing computations within multi-strain microbial consortia becomes increasingly beneficial. 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. We develop instead a consortium in which QS molecules are used to adjust gene expression at the single-cell level in response to the ratio of strains within the consortium, rather than the overall size of the population. We engineer this consortium by designing a multicellular circuit that extends the traditional co-repressive topology[30] to two strains. QS molecules from one strain induce the expression of a repressor in the opposite strain, shutting off production of its QS molecule
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