Publications by authors named "Gilles Bernot"

Article Synopsis
  • Time is crucial in biological systems like the cell cycle, but identifying parameters in differential equation models is challenging.
  • A new hybrid modeling framework is introduced, building on René Thomas' discrete modeling by adding "celerities" to measure time spent in each state.
  • This framework constructs a 5-variable model of the mammalian cell cycle, effectively capturing key behaviors such as quiescent phases and endoreplication while determining parameters through formal methods and timing observations.
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The usefulness of mathematical models for the biological regulatory networks relies on the predictive capability of the models in order to suggest interesting hypotheses and suitable biological experiments. All mathematical frameworks dedicated to biological regulatory networks must manage a large number of abstract parameters, which are not directly measurable in the cell. The cornerstone to establish predictive models is the identification of the possible parameter values.

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Cyclolipopeptides (CLPs) are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene (plcC) and not restored by plcC complementation.

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The relevance of biological materials and processes to computing-alias bioputing-has been explored for decades. These materials include DNA, RNA and proteins, while the processes include transcription, translation, signal transduction and regulation. Recently, the use of bacteria themselves as living computers has been explored but this use generally falls within the classical paradigm of computing.

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We analyze a basic building block of gene regulatory networks using a stochastic/geometric model in search of a mathematical backing for the discrete modeling frameworks. We consider a network consisting only of two interacting genes: a source gene and a target gene. The target gene is activated by the proteins encoded by the source gene.

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Article Synopsis
  • The paper enhances the modeling of biological regulatory networks by refining Rene Thomas's discrete approach, focusing on activation and inhibition delays.
  • It employs linear hybrid automata to better specify which variables are impacted more rapidly by changes in their regulators.
  • HyTech is utilized to automatically identify all paths between specified states and to create constraints on delay parameters for tracking specific pathways.
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Background: The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. We have investigated the general case of transport and metabolism as inspired by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) for glucose importation and by glycolysis.

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Background: As an alternative to the frequently used "reference design" for two-channel microarrays, other designs have been proposed. These designs have been shown to be more profitable from a theoretical point of view (more replicates of the conditions of interest for the same number of arrays). However, the interpretation of the measurements is less straightforward and a reconstruction method is needed to convert the observed ratios into the genuine profile of interest (e.

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The Hybrid Functional Petri Nets (HFPN) formalism has shown its convenience for modelling biological systems. This class of models has been fruitfully applied in biology but the remarkable expressiveness of HFPN often leads to incomplete validations. In this paper, we propose a logical framework for Timed Hybrid Petri Nets (THPN), a sub-class of HFPN.

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Background: Pseudomonas aeruginosa, an opportunistic pathogen, is often encountered in chronic lung diseases such as cystic fibrosis or chronic obstructive pneumonia, as well as acute settings like mechanical ventilation acquired pneumonia or neutropenic patients. It is a major cause of mortality and morbidity in these diseases. In lungs, P.

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Mucoidy and cytotoxicity arise from two independent modifications of the phenotype of the bacterium Pseudomonas aeruginosa that contribute to the mortality and morbidity of cystic fibrosis. We show that, even though the transcriptional regulatory networks controlling both processes are quite different from a molecular or mechanistic point of view, they may be identical from a dynamic point of view: epigenesis may in both cases be the cause of the acquisition of these new phenotypes. This was highlighted by the identity of formal graphs modelling these networks.

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Based on the discrete definition of biological regulatory networks developed by René Thomas, we provide a computer science formal approach to treat temporal properties of biological regulatory networks, expressed in computational tree logic. It is then possible to build all the models satisfying a set of given temporal properties. Our approach is illustrated with the mucus production in Pseudomonas aeruginosa.

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New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism.

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