Estimating the multi-scale effects of extrinsic noise on genes and circuits activity from an empirically validated model of transcription kinetics

Samuel Matos Dias Oliveira, Mohamed Mohamed Bahrudeen, Sofia Startceva, Andre Sanches Ribeiro

    Research output: Other conference contributionAbstractScientific

    Abstract

    Recent studies of Escherichia coli transcription dynamics using time-lapse confocal microscopy and in vivo single-RNA detection confirmed that transcription initiation has two main rate-limiting steps. Here, we argue that this allows selective ‘tuning’ of the effects of extrinsic noise on a multi-scale level that ranges from individual genes to large-scale gene networks. First, using empirically validated stochastic models of transcription and translation, we show that the effects of RNA polymerase numbers’ cell-to-cell variability on the cell-to-cell diversity in RNA numbers decrease as the relative time-length of the open complex formation increases. Next, using a stochastic model of a 2-genes symmetric toggle switch, we show that the cell-to-cell diversity of the switching frequency due to cell-to-cell variability in RNA polymerase numbers also depends on the promoter kinetics. Finally, from the binarized protein numbers over time of 50-gene network models where genes interact by repression, we calculate the cell-to-cell variability of the mutual information and Lempel-Ziv complexity of the networks dynamics, and find that, while arising from the cell-to-cell variability in RNA polymerase numbers, these variability levels also depend on the promoter initiation kinetics. Given this, we hypothesize that E. coli may be capitalizing on the 2 rate-limiting steps’ nature of transcription initiation to tune the effects of extrinsic noise at the single gene, motifs, and large gene regulatory network levels.
    Original languageEnglish
    Pages118-131
    Number of pages14
    Publication statusPublished - 19 Sep 2017
    EventItalian Workshop on Artificial Life and Evolutionary Computation -
    Duration: 1 Jan 2000 → …

    Conference

    ConferenceItalian Workshop on Artificial Life and Evolutionary Computation
    Period1/01/00 → …

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