Mapping the Operational Landscape of MicroRNAs in Synthetic Gene Circuits.

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dc.contributor.authorQuarton, Tyleren_US
dc.contributor.authorEhrhardt, Kristinaen_US
dc.contributor.authorLee, Jamesen_US
dc.contributor.authorKannan, Srijaaen_US
dc.contributor.authorLi, Yien_US
dc.contributor.authorMa, Lanen_US
dc.contributor.authorBleris, Leonidasen_US
dc.contributor.utdAuthorQuarton, Tyler
dc.contributor.utdAuthorEhrhardt, Kristina
dc.contributor.utdAuthorLee, James
dc.contributor.utdAuthorKannan, Srijaa
dc.contributor.utdAuthorLi, Yi
dc.contributor.utdAuthorMa, Lan
dc.contributor.utdAuthorBleris, Leonidas
dc.date.accessioned2018-10-22T19:29:03Z
dc.date.available2018-10-22T19:29:03Z
dc.date.created2018-10-22en_US
dc.date.issued2018-10-22
dc.description.abstractMicroRNAs are a class of short, noncoding RNAs that are ubiquitous modulators of gene expression, with roles in development, homeostasis, and disease. Engineered microRNAs are now frequently used as regulatory modules in synthetic biology. Moreover, synthetic gene circuits equipped with engineered microRNA targets with perfect complementarity to endogenous microRNAs establish an interface with the endogenous milieu at the single-cell level. The function of engineered microRNAs and sensor systems is typically optimized through extensive trial-and-error. Here, using a combination of synthetic biology experimentation in human embryonic kidney cells and quantitative analysis, we investigate the relationship between input genetic template abundance, microRNA concentration, and output under microRNA control. We provide a framework that employs the complete operational landscape of a synthetic gene circuit and enables the stepwise development of mathematical models. We derive a phenomenological model that recapitulates experimentally observed nonlinearities and contains features that provide insight into the microRNA function at various abundances. Our work facilitates the characterization and engineering of multi-component genetic circuits and specifically points to new insights on the operation of microRNAs as mediators of endogenous information and regulators of gene expression in synthetic biology.en_US
dc.description.sponsorshipUS National Science Foundation (NSF) CAREER grant 1351354, NSF 1361355.en_US
dc.identifier.bibliographicCitationQuarton, Tyler, Kristina Ehrhardt, James Lee, Srijaa Kannan, et al. 2018. "Mapping the operational landscape of microRNAs in synthetic gene circuits.." Npj Systems Biology And Applications 4: 6.en_US
dc.identifier.issn2056-7189en_US
dc.identifier.issue6
dc.identifier.urihttp://hdl.handle.net/10735.1/6209
dc.identifier.volume4en_US
dc.language.isoenen_US
dc.publisherNature Partner Journalsen_US
dc.relation.urihttps://dx.doi.org/10.1038/s41540-017-0043-yen_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2018 The Authors.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.source.journalnpj Systems Biology and Applicationsen_US
dc.subjectMicroRNAsen_US
dc.subjectRenal cellsen_US
dc.subjectGene Expressionen_US
dc.titleMapping the Operational Landscape of MicroRNAs in Synthetic Gene Circuits.en_US
dc.typeTexten_US
dc.type.genrearticleen_US

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