title: Cellular signaling circuits interfaced with synthetic, post-translational, negating Boolean logic devices.
abstract: A negating functionality is fundamental to information processing of logic circuits within cells and computers. Aiming to adapt unutilized electronic concepts to the interrogation of signaling circuits in cells, we first took a bottom-up strategy whereby we created protein-based devices that perform negating Boolean logic operations such as NOT, NOR, NAND, and N-IMPLY. These devices function in living cells within a minute by precisely commanding the localization of an activator molecule among three subcellular spaces. We networked these synthetic gates to an endogenous signaling circuit and devised a physiological output. In search of logic functions in signal transduction, we next took a top-down approach and computationally screened 108 signaling pathways to identify commonalities and differences between these biological pathways and electronic circuits. This combination of synthetic and systems approaches will guide us in developing foundations for deconstruction of intricate cell signaling, as well as construction of biomolecular computers.
authors.affiliation: Department of Biomedical Engineering, §Department of Cell Biology, and ⊥Center for Cell Dynamics, Johns Hopkins University School of Medicine , Baltimore, Maryland 21205, United States.
authors.forename: Shiva
authors.initials: S
authors.lastname: Razavi
authors.forename: Steven
authors.initials: S
authors.lastname: Su
authors.forename: Takanari
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000465:Algorithms; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019556:COS Cells; D002522:Chlorocebus aethiops; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008962:Models, Theoretical; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000097573:Red Fluorescent Protein
chemical_list: D000900:Anti-Bacterial Agents; D008164:Luminescent Proteins; D020123:Sirolimus; D022021:Tacrolimus Binding Proteins; D000097573:Red Fluorescent Protein
keywords: Rac; chemically induced dimerization; membrane ruffling; negation; signaling pathway; synthetic Boolean logic