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      Synchronizing genetic relaxation oscillators by intercell signaling

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      Proceedings of the National Academy of Sciences
      Proceedings of the National Academy of Sciences

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          Abstract

          The ability to design and construct synthetic gene regulatory networks offers the prospect of studying issues related to cellular function in a simplified context; such networks also have many potential applications in biotechnology. A synthetic network exhibiting oscillatory behavior has recently been constructed [Elowitz, M. B. & Leibler, S. (2000) Nature (London) 403, 335-338]. It has also been shown that a natural bacterial quorum-sensing mechanism can be used in a synthetic system to communicate a signal between two populations of cells, such that receipt of the signal causes expression of a target gene [Weiss, R. & Knight, T. F. (2000) in DNA6: Sixth International Meeting on DNA-Based Computers, June 13-17, 2000, Leiden, The Netherlands]. We propose a synthetic gene network in Escherichia coli which combines these two features: the system acts as a relaxation oscillator and uses an intercell signaling mechanism to couple the oscillators and induce synchronous oscillations. We model the system and show that the proposed coupling scheme does lead to synchronous behavior across a population of cells. We provide an analytical treatment of the synchronization process, the dominant mechanism of which is "fast threshold modulation."

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          Most cited references26

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          How bacteria talk to each other: regulation of gene expression by quorum sensing.

          Quorum sensing, or the control of gene expression in response to cell density, is used by both gram-negative and gram-positive bacteria to regulate a variety of physiological functions. In all cases, quorum sensing involves the production and detection of extracellular signalling molecules called autoinducers. While universal signalling themes exist, variations in the design of the extracellular signals, the signal detection apparatuses, and the biochemical mechanisms of signal relay have allowed quorum sensing systems to be exquisitely adapted for their varied uses. Recent studies show that quorum sensing modulates both intra- and inter-species cell-cell communication, and it plays a major role in enabling bacteria to architect complex community structures.
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            Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators.

            The importance of accurate demographic information is reflected in the United States Constitution, Article 1, which provides for a decennial census of this country's human population. Bacteria also conduct a census of their population and do so more frequently, more efficiently, and as far we know, with little if any of the political contentiousness caused by human demographers. Many examples have been found of particular bacterial genes, operons, or regulons that are expressed preferentially at high cell densities. Many of these are regulated by proteins related to the LuxR and LuxI proteins of Vibrio fischeri, and by a diffusible pheromone called an autoinducer. LuxR and LuxI and their cognate autoinducer (3-oxohexanoyl homoserine lactone, designated VAI-1) provide an important model to describe the functions of this family of proteins. LuxR is a VAI-1 receptor and a VAI-1-dependent transcriptional activator, and LuxI directs the synthesis of VAI-1. VAI-1 diffuses across the bacterial envelope, and intracellular concentrations of it are therefore strongly increased by nearby VAI-1-producing bacteria. Similar systems regulate pathogenesis factors in Pseudomonas aeruginosa and Erwinia spp., as well as T1 plasmid conjugal transfer in Agrobacterium tumefaciens, and many other genes in numerous genera of gram-negative bacteria. Genetic analyses of these systems have revealed a high degree of functional conservation, while also uncovering features that are unique to each.
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              Computational studies of gene regulatory networks: in numero molecular biology.

              Remarkable progress in genomic research is leading to a complete map of the building blocks of biology. Knowledge of this map is, in turn, setting the stage for a fundamental description of cellular function at the DNA level. Such a description will entail an understanding of gene regulation, in which proteins often regulate their own production or that of other proteins in a complex web of interactions. The implications of the underlying logic of genetic networks are difficult to deduce through experimental techniques alone, and successful approaches will probably involve the union of new experiments and computational modelling techniques.
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                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                Proceedings of the National Academy of Sciences
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                January 22 2002
                January 22 2002
                : 99
                : 2
                : 679-684
                Article
                10.1073/pnas.022642299
                117365
                11805323
                94ebacb0-9534-4e33-b426-1ba730a35546
                © 2002
                History

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