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dc.contributor.authorSadeghpour, Mehdi
Veliz-Cuba, Alan
Orosz, Gábor
Josić, Krešimir
Bennett, Matthew R.
dc.date.accessioned 2017-07-27T17:40:18Z
dc.date.available 2017-07-27T17:40:18Z
dc.date.issued 2017
dc.identifier.citation Sadeghpour, Mehdi, Veliz-Cuba, Alan, Orosz, Gábor, et al.. "Bistability and oscillations in co-repressive synthetic microbial consortia." Quantitative Biology, 5, no. 1 (2017) Springer: 55-66. https://doi.org/10.1007/s40484-017-0100-y.
dc.identifier.urihttps://hdl.handle.net/1911/95527
dc.description.abstract Background: Synthetic microbial consortia are conglomerations of genetically engineered microbes programmed to cooperatively bring about population-level phenotypes. By coordinating their activity, the constituent strains can display emergent behaviors that are difficult to engineer into isogenic populations. To do so, strains are engineered to communicate with one another through intercellular signaling pathways that depend on cell density. Methods: Here, we used computational modeling to examine how the behavior of synthetic microbial consortia results from the interplay between population dynamics governed by cell growth and internal transcriptional dynamics governed by cell-cell signaling. Specifically, we examined a synthetic microbial consortium in which two strains each produce signals that down-regulate transcription in the other. Within a single strain this regulatory topology is called a “co-repressive toggle switch” and can lead to bistability. Results: We found that in co-repressive synthetic microbial consortia the existence and stability of different states depend on population-level dynamics. As the two strains passively compete for space within the colony, their relative fractions fluctuate and thus alter the strengths of intercellular signals. These fluctuations drive the consortium to alternative equilibria. Additionally, if the growth rates of the strains depend on their transcriptional states, an additional feedback loop is created that can generate oscillations. Conclusions: Our findings demonstrate that the dynamics of microbial consortia cannot be predicted from their regulatory topologies alone, but are also determined by interactions between the strains. Therefore, when designing synthetic microbial consortia that use intercellular signaling, one must account for growth variations caused by the production of protein.
dc.language.iso eng
dc.publisher Springer
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer.
dc.title Bistability and oscillations in co-repressive synthetic microbial consortia
dc.type Journal article
dc.citation.journalTitle Quantitative Biology
dc.subject.keywordsynthetic biology
microbial consortia
quorum sensing
relaxation oscillations
dc.citation.volumeNumber 5
dc.citation.issueNumber 1
dc.identifier.digital Bistability_and_oscillations
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1007/s40484-017-0100-y
dc.identifier.pmcid PMC5508549
dc.identifier.pmid 28713623
dc.type.publication post-print
dc.citation.firstpage 55
dc.citation.lastpage 66


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