Engineering Repressors with Coevolutionary Cues Facilitates Toggle Switches with a Master Reset

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dc.contributor.authorDimas, R. P.
dc.contributor.authorJiang, Xian-Li
dc.contributor.authorAlberto de la Paz, Jose
dc.contributor.authorMorcos, Faruck
dc.contributor.authorChan, C. T. Y.
dc.contributor.utdAuthorJiang, Xian-Li
dc.contributor.utdAuthorAlberto de la Paz, Jose
dc.contributor.utdAuthorMorcos, Faruck
dc.date.accessioned2020-03-11T16:05:15Z
dc.date.available2020-03-11T16:05:15Z
dc.date.issued2019-04-24
dc.descriptionSupplementary material is included.
dc.description.abstractEngineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF signal that produces a unique behavior: each engineered biological activity is switched to a stable ON state by different chemicals and returned to OFF in response to a common signal. One promising application of this design is to develop living diagnostics for monitoring multiple parameters in complex physiological environments and it represents one of many circuit topologies that can be explored with modular repressors designed with coevolutionary information. © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.description.departmentErik Jonsson School of Engineering and Computer Science
dc.description.departmentCenter for Systems Biology
dc.description.sponsorshipUniversity of Texas System Rising STARs Program [802-1053-T000674F], Welch Foundation [Grant # BP-0037].
dc.identifier.bibliographicCitationDimas, R. P., X. -L Jiang, J. Alberto de la Paz, F. Morcos, et al. 2019. "Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset." Nucleic Acids Research 47(10): 5449-5463, doi: 10.1093/nar/gkz280
dc.identifier.issn1362-4962
dc.identifier.issue10
dc.identifier.urihttp://dx.doi.org/10.1093/nar/gkz280
dc.identifier.urihttps://hdl.handle.net/10735.1/7388
dc.identifier.volume47
dc.language.isoen
dc.publisherOxford University Press
dc.rightsCC BY-NC 4.0 (Attribution-NonCommercial)
dc.rights©2019 The Authors
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.source.journalNucleic Acids Research
dc.subjectMolecular recognition
dc.subjectBiological monitoring
dc.subjectRepressors, Genetic
dc.subjectSignal processing
dc.subjectAllosteric regulation
dc.subjectDNA
dc.subjectSynthetic biology
dc.subjectCloning
dc.titleEngineering Repressors with Coevolutionary Cues Facilitates Toggle Switches with a Master Reset
dc.type.genrearticle

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