title: Wiring Together Synthetic Bacterial Consortia to Create a Biological Integrated Circuit.
abstract: The promise of adapting biology to information processing will not be realized until engineered gene circuits, operating in different cell populations, can be wired together to express a predictable function. Here, elementary biological integrated circuits (BICs), consisting of two sets of transmitter and receiver gene circuit modules with embedded memory placed in separate cell populations, were meticulously assembled using live cell lithography and wired together by the mass transport of quorum-sensing (QS) signal molecules to form two isolated communication links (comlinks). The comlink dynamics were tested by broadcasting "clock" pulses of inducers into the networks and measuring the responses of functionally linked fluorescent reporters, and then modeled through simulations that realistically captured the protein production and molecular transport. These results show that the comlinks were isolated and each mimicked aspects of the synchronous, sequential networks used in digital computing. The observations about the flow conditions, derived from numerical simulations, and the biofilm architectures that foster or silence cell-to-cell communications have implications for everything from decontamination of drinking water to bacterial virulence.
authors.affiliation: University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Perry
authors.affiliation: University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Nelson
authors.affiliation: University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Gregory
authors.initials: G
authors.lastname: Timp
mesh_terms: D018441:Biofilms; D002450:Cell Communication; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D053263:Gene Regulatory Networks; D056656:Lab-On-A-Chip Devices; D050296:Microbial Viability; D000074041:Microorganisms, Genetically-Modified / Q000235:genetics; D008962:Models, Theoretical; D053038:Quorum Sensing; D058615:Synthetic Biology / Q000379:methods*
keywords: biological computing; cell−cell communication; quorum sensing; synthetic biofilm; synthetic biology