During aerobic growth on glucose, Escherichia coli excretes acetate, a mechanism called "overflow metabolism." At high concentrations, the secreted acetate inhibits growth. Several mechanisms have been proposed for explaining this phenomenon, but thorough analysis is hampered by diversity of experimental conditions and strains used in these studies. Here, we describe construction set isogenic that remove different parts metabolic network involved metabolism. Analysis reveals (i)...

The modeling and simulation of genetic regulatory networks have created the need for tools model validation. main challenges validation are achievement a match between precision predictions experimental data, as well efficient reliable comparison observations.We present an approach towards models addressing above challenges. It combines method qualitative with techniques checking, is supported by new version computer tool Genetic Network Analyzer (GNA). model-validation has been applied to...

Gene expression is controlled by the joint effect of (i) global physiological state cell, in particular activity gene machinery, and (ii) DNA‐binding transcription factors other specific regulators. We present a model‐based approach to distinguish between these two effects using time‐resolved measurements promoter activities. demonstrate strength analyzing circuit involved regulation carbon metabolism E. coli . Our results show that transcriptional response network cell signaling metabolite...

Article23 November 2015Open Access Source Data A synthetic growth switch based on controlled expression of RNA polymerase Jérôme Izard Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Saint Martin d'Hères, France INRIA, – Rhône-Alpes research center, Ismier, These authors contributed equally to this work Search for more papers by author Cindy DC Gomez Balderas Delphine Ropers Stephan Lacour Xiaohu Song Center Research and Interdisciplinarity, INSERM...

Abstract Motivation: Models of the dynamics cellular interaction networks have become increasingly larger in recent years. Formal verification based on model checking provides a powerful technology to keep up with this increase scale and complexity. The application modelchecking approaches is hampered, however, by difficulty for nonexpert users formulate appropriate questions temporal logic. Results: In order deal problem, we propose use patterns, that is, high-level query templates capture...

Abstract Background Fluorescent and luminescent reporter genes have become popular tools for the real-time monitoring of gene expression in living cells. However, mathematical models are necessary extracting biologically meaningful quantities from primary data. Results We present a rigorous method deriving relative protein synthesis rates (mRNA concentrations) concentrations by means kinetic expression. experimentally computationally validate this approach case Fis, global regulator...

Gene regulatory networks consist of direct interactions but also include indirect mediated by metabolites and signaling molecules. We describe how these can be derived from a model the underlying biochemical reaction network, using weak time-scale assumptions in combination with sensitivity criteria metabolic control analysis. apply this approach to carbon assimilation network Escherichia coli. Our results show that gene is densely connected, contrary what usually assumed. Moreover, largely...

Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation uncertain. The factor CsrA stated as being only regulator essential for use glycolytic substrates. A dozen enzymes central carbon metabolism (CCM) have been reported potentially controlled by CsrA, its impact on CCM functioning has not demonstrated. Here, multiscale analysis was performed wild-type strain and isogenic mutant attenuated...

Abstract Motivation Taxonomic analysis of environmental microbial communities is now routinely performed thanks to advances in DNA sequencing. Determining the role these global biogeochemical cycles requires identification their metabolic functions, such as hydrogen oxidation, sulfur reduction, and carbon fixation. These functions can be directly inferred from metagenomics data, but many applications metabarcoding still method choice. The reconstruction data integration into coarse-grained...

Splicing is a crucial step for human immunodeficiency virus, type 1 (HIV-1) multiplication; eight acceptor sites are used in competition to produce the vif, vpu, vpr, nef, env, tat, and rev mRNAs. The effects of SR proteins have only been investigated on limited number HIV-1 splicing by using small RNA pieces. To understand how influence use sites, we tested overproduction individual HeLa cells pattern an that contained all sites. steady state levels mRNAs produced were quantified reverse...

The human immunodeficiency virus, type 1, Tat protein plays a key role in virus multiplication. Because of its apoptotic property, production is highly controlled. It depends upon the A3 splicing site utilization. A control activity ESS2 silencer, which located within long stem-loop structure 3 (SLS3), far downstream from A3. Here, by enzymatic footprints, we demonstrate presence several heterogeneous nuclear ribonucleoprotein (hnRNP) A1-binding sites on SLS3 and show importance C-terminal...

ABSTRACT In the bacterium Escherichia coli , posttranscriptional regulatory system Csr was postulated to influence transition from glycolysis gluconeogenesis. Here, we explored role of in glucose-acetate as a model glycolysis-to-gluconeogenesis switch. Mutations reorganization gene expression after glucose exhaustion and disturb timing acetate reconsumption exhaustion. Analysis metabolite concentrations during revealed that has major effect on energy levels cells This demonstrated result...

Carbon catabolite repression (CCR) controls the order in which different carbon sources are metabolised. Although this system is one of paradigms regulation bacteria, underlying mechanisms remain controversial. CCR involves coordination subsystems cell - responsible for uptake sources, their breakdown production energy and precursors, conversion latter to biomass. The complexity integrated system, with regulatory cutting across metabolism, gene expression, signalling, has motivated important...

The adaptation of the bacterium Escherichia coli to carbon starvation is controlled by a large network biochemical reactions involving genes, mRNAs, proteins, and signalling molecules. dynamics these networks difficult analyze, notably due lack quantitative information on parameter values. To overcome limitations, model reduction approaches based quasi-steady-state (QSS) piecewise-linear (PL) approximations have been proposed, resulting in models that are easier handle mathematically...

Alternative splicing plays a key role in the production of numerous proteins by complex lentiviruses such as HIV-1. The study HIV-1 RNA has provided useful information not only about physiology virus, but also general mechanisms that regulate mammalian pre-mRNA alternative splicing. Like all retroviruses, fraction transcripts remains intact to serve genomic and code for Gag Gag-Pol protein precursors. In addition, is important controlling some viral proteins, which could otherwise have...

Abstract Motivation: Time-series observations from reporter gene experiments are commonly used for inferring and analyzing dynamical models of regulatory networks. The robust estimation promoter activities protein concentrations primary data is a difficult problem due to measurement noise the indirect relation between measurements quantities biological interest. Results: We propose general approach based on regularized linear inversion solve range problems in analysis data, notably inference...

Bacteria have to continuously adjust nutrient fluctuations from favorable less-favorable conditions and in response carbon starvation. The glucose-acetate transition followed by starvation is representative of such observed Escherichia coli many environments. Regulation gene expression through fine-tuning mRNA pools constitutes one the regulation levels required for a metabolic adaptation. It results both transcription degradation controls. However, contribution transcript stability poorly...