title: A programmable NOR-based device for transcription profile analysis.
abstract: An autonomous synthetic programmable device that can diagnose a cell's state according to predefined markers and produce a corresponding therapeutic output may be the basis of future programmable drugs. Motivated to increase diagnosis precision, devices that integrate multiple disease markers have been implemented based on various molecular tools. As simplicity is key to future in-vivo applications, we sought a molecular device that a) integrates multiple inputs without requiring pairwise interactions, and b) harnesses only mechanisms that cells natively use. Here we show a synthetic NOR-based programmable device, operating via a biochemical obstructing approach rather than on a constructive approach, capable of differentiating between prokaryotic cell strains based on their unique expression profile. To demonstrate our system's strengths we further implemented the NOT, OR and AND gates. The device's programmability allows context-dependent selection of the inputs being sensed, and of the expressed output, thus, holding great promise in future biomedical applications.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tom
authors.initials: T
authors.lastname: Ran
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Douek
authors.forename: Lilach
authors.initials: L
authors.lastname: Milo
authors.forename: Ehud
authors.initials: E
authors.lastname: Shapiro
mesh_terms: D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000096:biosynthesis; D020869:Gene Expression Profiling / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011933:Reagent Kits, Diagnostic; D014157:Transcription Factors / Q000096:biosynthesis; D059467:Transcriptome
chemical_list: D029968:Escherichia coli Proteins; D011933:Reagent Kits, Diagnostic; D014157:Transcription Factors; D049452:Green Fluorescent Proteins