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Modular, robust, and extendible multicellular circuit design in yeast

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dc.contributor.authorCarignano, Albertoen
dc.contributor.authorChen, Dai Huaen
dc.contributor.authorMallory, Cannonen
dc.contributor.authorWright, R. Clayen
dc.contributor.authorSeelig, Georgen
dc.contributor.authorKlavins, Ericen
dc.date.accessioned2022-07-12T12:44:43Zen
dc.date.available2022-07-12T12:44:43Zen
dc.date.issued2022-03-21en
dc.description.abstractDivision of labor between cells is ubiquitous in biology but the use of multicellular consortia for engineering applications is only beginning to be explored. A significant advantage of multicellular circuits is their potential to be modular with respect to composition but this claim has not yet been extensively tested using experiments and quantitative modeling. Here, we construct a library of 24 yeast strains capable of sending, receiving or responding to three molecular signals, characterize them experimentally and build quantitative models of their input-output relationships. We then compose these strains into two- and three-strain cascades as well as a four-strain bistable switch and show that experimentally measured consortia dynamics can be predicted from the models of the constituent parts. To further explore the achievable range of behaviors, we perform a fully automated computational search over all two-, three-, and four-strain consortia to identify combinations that realize target behaviors including logic gates, band-pass filters, and time pulses. Strain combinations that are predicted to map onto a target behavior are further computationally optimized and then experimentally tested. Experiments closely track computational predictions. The high reliability of these model descriptions further strengthens the feasibility and highlights the potential for distributed computing in synthetic biology.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.7554/eLife.74540en
dc.identifier.issn2050-084Xen
dc.identifier.othere74540en
dc.identifier.pmid35312478en
dc.identifier.urihttp://hdl.handle.net/10919/111212en
dc.identifier.volume11en
dc.language.isoenen
dc.publishereLife Sciencesen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectsynthetic multicellular circuiten
dc.subjectparallel computingen
dc.subjectautomated circuit designen
dc.titleModular, robust, and extendible multicellular circuit design in yeasten
dc.title.serialeLifeen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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