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While many articles have analyzed the effectiveness of the policies that aimed to limit the spread of COVID-19, very little research work has examined the determinants that drove these policies. Therefore, we proposed to study the determinants that led government authorities to implement more or less restrictive policies to limit the spread of the pandemic. Using the COVID-19 stringency index, we highlighted a positive effect of the incidence rate on the stringency level. Patient capacity in intensive care units was also a key variable. This is indicative of the capacity of countries to have a sufficient and appropriate health system to absorb such pandemic crises. On the other hand, we show that epidemiological data regarding the risk of excess mortality (diabetes, cancer, and cardiovascular pathologies) had a negative effect. We conclude by recalling the importance of policy coordination between countries when it comes to lowering the stringency levels of measures, in order to avoid a resurgence of the epidemic.

International audience; Meriones shawi (M.shawi) is the main reservoir host for zoonotic cutaneous leishmaniasis (ZCL) in Central Tunisia. The incorporation of environmental and climatic effects on the spread of ZCL in M. shawi remains difficult. This study presents an agent-based model (ABM) to overcome these difficulties and examine the impact of environment (i.e. vegetation cover) and climate (i.e. temperature) on M. shawi movement and prevalence. The model simulation considers two agent types: rodent agent and field unit agent. We tested the model according to two types of rodent movement: random and thoughtful. We integrated time dependent normalized difference vegetation index (NDVI) in order to test the land cover effects on rodent movement and ZCL transmission. The results confirmed that the spread of the disease depends on rodent movement. We observed that prevalence and distribution are the closest to field data when the vegetation cover is highest and that rodents go for thoughtful movement. In addition, we found that the nature of movement (random or thoughtful) and prevalence depends strongly on minimum food detection.

Background The epidemiological pattern of hepatitis A infection has shown dynamic changes in many parts of the world due to improved socio-economic conditions and the accumulation of seronegative subjects, which leads to possible outbreaks and increased morbidity rate. In Tunisia, the epidemiological status of hepatits A virus is currently unknown. However, over the past years higher numbers of symptomatic hepatitis A virus infection in school attendants and several outbreaks were reported to the Ministry of Health, especially from regions with the lowest socio-economic levels in the country. The aim of this study was to investigate the current seroprevalence of hepatitis A virus antibodies in central-west Tunisia and assess the impact of hepatitis A virus vaccination on hepatitis A epidemiology. Methods Serum samples from 1379 individuals, aged 5–75 years, were screened for hepatitis A virus antibodies. Adjusted seroprevalence, incidence and force of infection parameters were estimated by a linear age structured SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. A vaccine model was then constructed to assess the impact on hepatitis A virus epidemiology of 3 scenarios of vaccination strategies: one dose at 12-months of age, one dose at 6-years and one dose at 12-months and another at 6-years of age during 6 years. Results A rapid increase in anti-hepatitis A virus seroprevalence was noted during infancy and adolescence: 47% of subjects under 10-years-old are infected; the prevalence increases to 77% at 15-years and reaches 97% in subjects aged 30-years. The force of infection is highest between 10 and 30-years of age and the incidence declines with increasing age. The vaccine model showed that the 3-scenarios lead to a significant reduction of the fraction of susceptibles. The two doses scenario gives the best results. Single-dose vaccination at 6-years of age provides more rapid decrease of disease burden in school-aged children, as compared to single-dose vaccination at 12-months, but keeps with a non-negligible fraction of susceptibles among children Conclusions Our study confirms the epidemiological switch from high to intermediate endemicity of hepatitis A virus in Tunisia and provides models that may help undertake best decisions in terms of vaccinations strategies.

International audience; Both empirical and theoretical studies, have dealt with the question how to best optimize reproductive fitness for hermaphrodites, using models such as game theory or complicated energetic costs and benefits of mating displays. However, hermaphrodites exhibit a broad spectrum of sexual behaviors like simultaneous, sequential or lifetime gonochorist that cannot be explained using a unique formalism. A possible explanation of this diversity relies on the way these species maximize their fitness: Does the individual hermaphrodite split its time between strategies maximizing its instantaneous reproductive fitness or its evolutionary fitness? Here, we compare these two points of view and extend a game theoretical formalism to a sex allocation model that underlies all sexual behaviors as a result of a dynamic game whose payoff depends on the costs and benefits of sexual reproduction. Using this formalism, we prove that a simultaneous hermaphrodites strategy is stable even for high values of sex changing costs. Moreover, we prove that the stability of a sequential hermaphrodite is linked to the average energy allocated to the pure female strategy.

International audience; Networks used in biological applications at different scales (molecule, cell and population) are of different types: neuronal, genetic, and social, but they share the same dynamical concepts, in their continuous differential versions (e.g., non-linear Wilson-Cowan system) as well as in their discrete Boolean versions (e.g., non-linear Hopfield system); in both cases, the notion of interaction graph G(J) associated to its Jacobian matrix J, and also the concepts of frustrated nodes, positive or negative circuits of G(J), kinetic energy, entropy, attractors, structural stability, etc., are relevant and useful for studying the dynamics and the robustness of these systems. We will give some general results available for both continuous and discrete biological networks, and then study some specific applications of three new notions of entropy: (i) attractor entropy, (ii) isochronal entropy and (iii) entropy centrality; in three domains: a neural network involved in the memory evocation, a genetic network responsible of the iron control and a social network accounting for the obesity spread in high school environment.

International audience; (1) Background: The aim of this paper is to show that e-health tools like smart homes allow the personalization of the surveillance and preventive education of chronic patients, such as obese persons, in order to maintain a comfortable and preventive lifestyle at home. (2) Technologies and methods: Several types of sensors allow coaching the patient at home, e.g., the sensors recording the activity and monitoring the physiology of the person. All of this information serves to personalize serious games dedicated to preventive education, for example in nutrition and vision. (3) Results: We built a system of personalized preventive education at home based on serious games, derived from the feedback information they provide through a monitoring system. Therefore, it is possible to define (after clustering and personalized calibration) from the at home surveillance of chronic patients different comfort zones where their behavior can be estimated as normal or abnormal and, then, to adapt both alarm levels for surveillance and education programs for prevention, the chosen example of application being obesity.

International audience; We investigate the existence and stability of sexual strategies (sequential hermaphrodite, successive hermaphrodite or gonochore) at a proximate level. To accomplish this, we constructed and analyzed a general dynamical game model structured by size and sex. Our main objective is to study how costs of changing sex and of sexual competition should shape the sexual behavior of a hermaphrodite. We prove that, at the proximate level, size alone is insufficient to explain the tendency for a pair of prospective copulants to elect the male sexual role by virtue of the disparity in the energetic costs of eggs and sperm. In fact, we show that the stability of sequential vs. simultaneous hermaphrodite depends on sex change costs, while the stability of protandrous vs. protogynous strategies depends on competition cost.

A major challenge in ecological modeling of complex living system, is the integration of different models that describe the same phenomenon at different levels (physiological and ecological levels). The multi-agent paradigm provides an intuitive approach to model and simulate individual metabolism (Dynamic Energy Budget (DEB) model) and sexual behavior (Sex allocation model) and connect them to population-level proprieties. In this work, we model the energetic and sexual behavior of hermaphrodite species to determine the optimal size of sex change. For this purpose, we consider population dynamics and individuals evolutionary traits. Sex change size is seen as an emerging traits from both the set of intra-individual physiological traits, and inter-individual interactions. We develop an evolutionary individual-based model implementing these two models with a simple genetic algorithm to determine the optimal sex change size. The model description follows the ODD (Overview, Design concepts, Details) protocol, it is simulated with NetLogo platform and it is parametrized for Dusky grouper (Epinephelus marginatus). For this hermaphrodite species, both growth and maturation predicted by the model fit well with field observations.

For many diseases, research has shown a correlation between social organization and disease's spread. Thus, some diseases that are not infectious such as obesity, have been declared by the World Health Organization as an epidemic. The aim of this paper, is to study obesity models and to investigate on obesity factors evoked in the literature. Therefore we realized a search of models using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, then we exposed some of them using ODD protocol. As a result of this sysematic review, 106 studies were selected. Then, obesity determinants figured out were classified into environmental, psychological and behavioral, and biological factors.

Mohamed Alibi's presentation at the ISCB Student Council Symposium-Africa 2015, Dar es Salaam, Tanzania

Background Leishmania (L.) are intracellular protozoan parasites able to survive and replicate in the hostile phagolysosomal environment of infected macrophages. They cause leishmaniasis, a heterogeneous group of worldwide-distributed affections, representing a paradigm of neglected diseases that are mainly embedded in impoverished populations. To establish successful infection and ensure their own survival, Leishmania have developed sophisticated strategies to subvert the host macrophage responses. Despite a wealth of gained crucial information, these strategies still remain poorly understood. MicroRNAs (miRNAs), an evolutionarily conserved class of endogenous 22-nucleotide non-coding RNAs, are described to participate in the regulation of almost every cellular process investigated so far. They regulate the expression of target genes both at the levels of mRNA stability and translation; changes in their expression have a profound effect on their target transcripts. Methodology/Principal Findings We report in this study a comprehensive analysis of miRNA expression profiles in L. major-infected human primary macrophages of three healthy donors assessed at different time-points post-infection (three to 24 h). We show that expression of 64 out of 365 analyzed miRNAs was consistently deregulated upon infection with the same trends in all donors. Among these, several are known to be induced by TLR-dependent responses. GO enrichment analysis of experimentally validated miRNA-targeted genes revealed that several pathways and molecular functions were disturbed upon parasite infection. Finally, following parasite infection, miR-210 abundance was enhanced in HIF-1α-dependent manner, though it did not contribute to inhibiting anti-apoptotic pathways through pro-apoptotic caspase-3 regulation. Conclusions/Significance Our data suggest that alteration in miRNA levels likely plays an important role in regulating macrophage functions following L. major infection. These results could contribute to better understanding of the dynamics of gene expression in host cells during leishmaniasis., Author Summary Leishmania parasites belong to different species, each one characterized by specific vectors and reservoirs, and causes cutaneous or visceral disease(s) of variable clinical presentation and severity. In its mammalian host, the parasite is an obligate intracellular pathogen infecting the monocyte/macrophage lineage. Leishmania have developed ambiguous relationships with macrophages. Indeed, these cells are the shelter of invading parasites, where they will grow and eventually will reside in a silent state for life. But macrophages are also the cells that participate, through the induction of several pro-inflammatory mediators and antigen presentation, to shape the host immune response and ultimately kill the invader. To subvert these anti-parasite responses, Leishmania manipulate the host machinery for their own differentiation and survival. We aimed to evaluate the impact of L. major (the causative agent of zoonotic cutaneous leishmaniasis) infection on deregulation of non-coding miRNAs, a class of important regulators of gene expression. Our results revealed the implication of several miRNAs on macrophage fate upon parasite infection through regulation of different pathways, including cell death. Our findings provided a new insight for understanding mechanisms governing this miRNA deregulation by parasite infection and will help to provide clues for the development of control strategies for this disease.

For orientation preserving-homeomorphisms of the 2-disk, we consider the forcing relation among braid types of periodic orbits. We show that if a braid type forces a braid type , then either is an extension of or forces infinitely many extensions of . This generalizes a well known result in one-dimensional dynamics.

We analyzed the transcriptional signatures of mouse bone marrow-derived macrophages at different times after infection with promastigotes of the protozoan parasite Leishmania major. Ingenuity Pathway Analysis revealed that the macrophage metabolic pathways including carbohydrate and lipid metabolisms were among the most altered pathways at later time points of infection. Indeed, L. major promastiogtes induced increased mRNA levels of the glucose transporter and almost all of the genes associated with glycolysis and lactate dehydrogenase, suggesting a shift to anaerobic glycolysis. On the other hand, L. major promastigotes enhanced the expression of scavenger receptors involved in the uptake of Low-Density Lipoprotein (LDL), inhibited the expression of genes coding for proteins regulating cholesterol efflux, and induced the synthesis of triacylglycerides. These data suggested that Leishmania infection disturbs cholesterol and triglycerides homeostasis and may lead to cholesterol accumulation and foam cell formation. Using Filipin and Bodipy staining, we showed cholesterol and triglycerides accumulation in infected macrophages. Moreover, Bodipy-positive lipid droplets accumulated in close proximity to parasitophorous vacuoles, suggesting that intracellular L. major may take advantage of these organelles as high-energy substrate sources. While the effect of infection on cholesterol accumulation and lipid droplet formation was independent on parasite development, our data indicate that anaerobic glycolysis is actively induced by L. major during the establishment of infection., Author Summary Leishmania are obligated intracellular pathogens that develop almost exclusively in macrophages. Experimental leishmaniasis in mice is one of the most extensively studied models of intracellular infections both at the level of the parasite and host immune responses. We took advantage of Balb/c mice model to investigate gene expression profile through Affymetrix oligonucleotide arrays. In order to have a general and dynamic picture of the complex biological events that are acting in the context of Leishmania intracellular parasitism, we investigated the mouse macrophage response to initial invasion of L. major over a time course that extended from one to 24 hours post-infection. Our results reveal the alteration of several biological processes and metabolic changes. Indeed, similarly to different other pathogens, Leishmania induces cholesterol accumulation and foam cell formation that have been confirmed by confocal microscopy experiments. Whether Leishmania parasites take advantage of this high-energy source is now under investigation. Our findings provided further understandings in host responses to Leishmania infection.

Let f be a C1+ in orientation preserving diffeomorphism of the two-disk with positive topological entropy. The authors define for f an interval of topological invariants. Each point in this interval describes the way the elements of an infinite sequence of periodic orbits with arbitrarily large periods, are asymptotically linked one around the other.

29th Conference of the French-Speaking-Society-for-Theoretical-Biology, St Flour, FRANCE, jun4-17, 2009; International audience; Dusky groupers (Epinephelus marginatus) are characterized by a complex sex allocation strategies and overexploitation of bigger individuals. We developed an individual based model to investigate the long-term effects of density dependence on grouper population dynamics and to analyze the variabilities of extinction probabilities as a result of interacting mortalities at different life stages. We conduct several simulations with different forms of sex allocation functions and different combinations of mortality rates. The model was parametrized using data on dusky grouper populations from the literature. The most important insights produced by this simulation study are that density dependence of sex allocation is an evolutionarily stable strategy, increases the population biomass, mitigates the effect of the removal of large male and indicates a need for protection of females and flexible stages.

This chapter reports a variety of molecular biology informatics and mathematical methods that model the cell response to pathogens. The authors first outline the main steps of the immune response, then list the high throughput biotechnologies, generating a wealth of information on the infected cell and some of the immune-related databases; and finally explain how to extract meaningful information from these sources. The modelling aspect is divided into modelling molecular interaction and regulatory networks, through dynamic Boolean and Bayesian models, and modelling biochemical networks and regulatory networks, through Differential/Difference Equations. The interdisciplinary approach explains how to construct a model that mimics the cell’s dynamics and can predict the evolution and the outcome of infection.

The definition of theoretical biology may be controversial. Indeed, the basic definition of theoretical biology classifies it as biomathematics. It assumes that theoretical biology is divided into, at least, four subfields: Biological mathematical modeling, Relational biology/Complex systems biology, Bioinformatics and Biomodeling Computation. In epistemology, theoretical biology is defined as the action of ‘‘theorizing’’ life sciences. It aims to introduce laws; it highlights some biological phenomena and makes possible the identification of new biological principles. The latter definition does not imply a direct relationship with mathematics. In both cases, theoretical biology is a strongly multidisciplinary science, for the tools imported from other science and for the shared ideas. This controversy was one of the main concerns of the French-speaking Society for Theoretical Biology (SFBT). In 1985, it succeeded the Association for the development of Theoretical Methods for Biology (AMTB). The initial purpose of AMTB was to organize Schools; rapidly it took a more general objective: ‘‘the development of methods and theoretical formalisms useful for fundamental biological research and its practical applications’’. The origin of SFBT Conferences comes from 1975, when Jean-Henri Maresquelle, used to invite colleagues with different scientific backgrounds to round tables, twice a year. These meetings lead to scientifically fruitful multidisciplinary

Background Leishmania are obligated intracellular pathogens that replicate almost exclusively in macrophages. The outcome of infection depends largely on parasite pathogenicity and virulence but also on the activation status and genetic background of macrophages. Animal models are essential for a better understanding of pathogenesis of different microbes including Leishmania. Results Here we compared the transcriptional signatures of resistant (C57BL/6) and susceptible (BALB/c) mouse bone marrow-derived macrophages in response to Leishmania major (L. major) promastigotes infection. Microarray results were first analyzed for significant pathways using the Kyoto Encylopedia of Genes and Genomes (KEGG) database. The analysis revealed that a large set of the shared genes is involved in the immune response and that difference in the expression level of some chemokines and chemokine receptors could partially explain differences in resistance. We next focused on up-regulated genes unique to either BALB/c or C57BL/6 derived macrophages and identified, using KEGG database, signal transduction pathways among the most relevant pathways unique to both susceptible and resistant derived macrophages. Indeed, genes unique to C57BL/6 BMdMs were associated with target of rapamycin (mTOR) signaling pathway while a range of genes unique to BALB/c BMdMs, belong to p53 signaling pathway. We next investigated whether, in a given mice strain derived macrophages, the different up-regulated unique genes could be coordinately regulated. Using GeneMapp Cytoscape, we showed that the induced genes unique to BALB/c or C57BL/6 BMdMs are interconnected. Finally, we examined whether the induced pathways unique to BALB/c derived macrophages interfere with the ones unique to C57BL/6 derived macrophages. Protein-protein interaction analysis using String database highlights the existence of a cross-talk between p53 and mTOR signaling pathways respectively specific to susceptible and resistant BMdMs. Conclusions Taken together our results suggest that strains specific pathogenesis may be due to a difference in the magnitude of the same pathways and/or to differentially expressed pathways in the two mouse strains derived macrophages. We identify signal transduction pathways among the most relevant pathways modulated by L. major infection, unique to BALB/c and C57BL/6 BMdM and postulate that the interplay between these potentially interconnected pathways could direct the macrophage response toward a given phenotype.

Background: On March 11, 2020, the WHO announced that the COVID-19 outbreak had become pandemic, indicating that it was au- tonomous on several continents. Tunisia’s targeted containment and screen- ing strategy aligns with the WHO’s initial guidelines. This method is now showing its limitations. Mass screening in some countries shows that asymptomatic patients play an important role in spreading the virus through the population.Objective: Our goals are first to assess Tunisia’s COVID-19 control policies, and then understand the effect of various detection, quarantine and confinement strategies and the rule of asymptomatic patients on the spread of the virus in the Tunisian population. Methods: We develop and analyze a mathematical and epidemiologi- cal models for COVID- 19 in Tunisia. The data come from the Tunisian Health Commission dataset. Results: We calibrate different parameters of the model based on the Tunisian data, we calculate the expression of the basic reproduction num- ber R0 as a function of the model parameters and, finally, we carry out simulations of interventions and compare different strategies for suppress- ing and controlling the epidemic. Conclusions: We show that Tunisia’s control policies are effective in screening infected and asymptomatic persons.

International audience; BACKGROUND: Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. RESULTS: We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. CONCLUSION: Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.

The first chapter is devoted to basic biological and mathematical concepts, where we developed our conceptual approach and tried to form a generic definition of cancer. The second chapter aims to identify the optimal concentration of the treatment, while taking into consideration the patient biological profile and the molecular characteristics of the disease. This chapter presents a new approach to modeling tumor dynamics and its response to therapy based on the DEB (Dynamic Energy Budget) theory. In Chapter 3, the designed model is based on the cancer stem cells (CSC) hypothesis and takes into account the tumor heterogeneity. In addition, this chapter comes within the framework of new therapeutic trends, where we consider cancer as a chronic disease that must be treated like any other chronic disease. The major objective of this chapter is to identify an optimal schedule for the administration of therapeutic agents using optimal control theory. The previous model was expanded in Chapter 4 to consider the dedifferentiation of CSCs, which allowed us to model the resistance to treatment and the tumor adaptation. Chapter 5 aims to introduce a new modeling method based on polynomial dynamic systems on finite fields. This approach allows us to introduce the molecular level.; Le premier chapitre est consacré aux concepts de base biologiques et mathématiques, où nous avons développé notre approche conceptuelle et essayé de former une définition générique du cancer. Le deuxième chapitre a pour objectif de trouver et d’identifier la concentration optimale de la dose du traitement à administrer au patient, tout en prenant en considération son profil biologique et les caractéristiques moléculaires de la maladie. Ce chapitre présente une nouvelle approche de modélisation de la dynamique tumorale et de la réponse au traitement en se basant sur la théorie DEB (Dynamic Energy Budget). Dans le chapitre 3, le modèle conçu est basé sur l’hypothèse des cellules souches cancéreuses (CSC) et prend en compte l’hétérogénéité de la tumeur. De plus, ce chapitre rentre dans le cadre des nouvelles tendances thérapeutiques, où nous qualifions le cancer comme une maladie chronique qui doit être traitée comme toute autre maladie chronique. L’objectif majeur de ce chapitre est d’identifier un calendrier optimal pour l’administration des agents thérapeutiques en utilisant la théorie du contrôle optimal. Le modèle précédent a été étendu dans le chapitre 4 de manière à ce qu’il prenne en considération la dédifférenciation des CSC, ce qui nous a permis de modéliser la résistance au traitement et l’adaptation de la tumeur. Le chapitre 5, a pour but d’introduire une nouvelle méthode de modélisation basée sur les systèmes dynamiques polynomiaux sur des corps finis. Cette approche nous permet d’introduire le niveau moléculaire, complémentaire au niveau cellulaire, traité dans les chapitres précédents.

The objective of this thesis is to propose an approach for coupling metabolic and ecological levels in a complex biological system. This approach is presented as formal model describing the organism metabolism , which, thanks to DEVS formalism (Discrete Event System Specification), allows a coupling with models of interaction between organisms and between organisms and their environment. A study of the different modeling paradigms allowed us to identify, on the one hand the appropriate paradigm for each level and on the other hand the coupling factors formed by the variables at the interface of individual's internal and external worlds. This coupling explores the effect of lower-level dynamics on the emergence of higher-level characteristics. Two multiagent models, the first on sexual allocation and the second on optimal foraging, concretize the physiology/ecology coupling and show that this coupling makes it possible to connect the individual's internal world with its external world. The strong coupling, in the sense of model integration, explored in a first phase, was improved by the proposal of a formal model, called DEB-DEVS, of the metabolic model (of the Dynamic Energy Budget Theory (DEB)) common to the previous models. This proposal is the result of a reflection on the representation of internal dynamics of agents in ecological models. DEB-DEVS has been illustrated by two classical models of theoretical ecology.; L'objectif de cette thèse est de proposer une approche de couplage des niveaux métabolique et écologique dans un système biologique complexe. Cette approche se présente sous la forme d'un modèle formel décrivant le métabolisme d'un organisme vivant, qui grâce au formalisme DEVS (Discret Event System Specification) adopté, permet un couplage avec des modèles d'interaction entre les organismes et entre l'organisme et son environnement. Une étude des différents paradigmes de modélisation, nous a permis d'identifier d'un côté le paradigme adéquat pour chaque niveau et d'un autre côté les facteurs de couplage formés par les variables à l'interface des mondes internes et externes d'un individu. Ce couplage permet d'explorer l'effet de la dynamique du niveau inférieur sur l'émergence des caractéristiques du niveau supérieur. Deux modèles multi-agents, le premier sur l'allocation sexuelle et le deuxième sur la recherche optimale de nourriture, concrétisent le couplage physiologie/écologie et montrent que ce couplage permet de relier le monde interne de l'individu à son monde externe. Le couplage fort, dans le sens de l'intégration des modèles, exploré dans une première phase, a été amélioré par la proposition d'un modèle formel, nommé DEB-DEVS, du modèle métabolique (de la théorie du budget d'énergie dynamique (DEB)) commun aux modèles précédents. Cette proposition est le résultat d'une réflexion sur la représentation de la dynamique interne des agents dans des modèles de l'écologie. DEB-DEVS a été illustré par deux modèles classiques de l'écologie théorique.

The objective of this thesis is to propose an approach for coupling metabolic and ecological levels in a complex biological system. This approach is presented as formal model describing the organism metabolism , which, thanks to DEVS formalism (Discrete Event System Specification), allows a coupling with models of interaction between organisms and between organisms and their environment.A study of the different modeling paradigms allowed us to identify, on the one hand the appropriate paradigm for each level and on the other hand the coupling factors formed by the variables at the interface of individual's internal and external worlds. This coupling explores the effect of lower-level dynamics on the emergence of higher-level characteristics. Two multiagent models, the first on sexual allocation and the second on optimal foraging, concretize the physiology/ecology coupling and show that this coupling makes it possible to connect the individual's internal world with its external world. The strong coupling, in the sense of model integration, explored in a first phase, was improved by the proposal of a formal model, called DEB-DEVS, of the metabolic model (of the Dynamic Energy Budget Theory (DEB)) common to the previous models. This proposal is the result of a reflection on the representation of internal dynamics of agents in ecological models. DEB-DEVS has been illustrated by two classical models of theoretical ecology.; L'objectif de cette thèse est de proposer une approche de couplage des niveaux métabolique et écologique dans un système biologique complexe. Cette approche se présente sous la forme d'un modèle formel décrivant le métabolisme d'un organisme vivant, qui grâce au formalisme DEVS (Discret event System Specification) adopté, permet un couplage avec des modèles d'interaction entre les organismes et entre l'organisme et son environnement.Une étude des différents paradigmes de modélisation, nous a permis d'identifier d'un côté le paradigme adéquat pour chaque niveau et d'un autre côté les facteurs de couplage formés par les variables à l'interface des mondes internes et externes d'un individu. Ce couplage permet d'explorer l'effet de la dynamique du niveau inférieur sur l'émergence des caractéristiques du niveau supérieur. Deux modèles multi-agents, le premier sur l'allocation sexuelle et le deuxième sur la recherche optimale de nourriture, concrétisent le couplage physiologie/écologie et montrent que ce couplage permet de relier le monde interne de l'individu à son monde externe. Le couplage fort, dans le sens de l'intégration des modèles, exploré dans une première phase, a été amélioré par la proposition d'un modèle formel, nommé DEB-DEVS, du modèle métabolique (de la théorie du budget d'énergie dynamique (DEB)) commun aux modèles précédents. Cette proposition est le résultat d'une réflexion sur la représentation de la dynamique interne des agents dans des modèles de l'écologie. DEB-DEVS a été illustré par deux modèles classiques de l'écologie théorique.

The objective of this thesis is to propose an approach for coupling metabolic and ecological levels in a complex biological system. This approach is presented as formal model describing the organism metabolism , which, thanks to DEVS formalism (Discrete Event System Specification), allows a coupling with models of interaction between organisms and between organisms and their environment. A study of the different modeling paradigms allowed us to identify, on the one hand the appropriate paradigm for each level and on the other hand the coupling factors formed by the variables at the interface of individual's internal and external worlds. This coupling explores the effect of lower-level dynamics on the emergence of higher-level characteristics. Two multiagent models, the first on sexual allocation and the second on optimal foraging, concretize the physiology/ecology coupling and show that this coupling makes it possible to connect the individual's internal world with its external world. The strong coupling, in the sense of model integration, explored in a first phase, was improved by the proposal of a formal model, called DEB-DEVS, of the metabolic model (of the Dynamic Energy Budget Theory (DEB)) common to the previous models. This proposal is the result of a reflection on the representation of internal dynamics of agents in ecological models. DEB-DEVS has been illustrated by two classical models of theoretical ecology.; L'objectif de cette thèse est de proposer une approche de couplage des niveaux métabolique et écologique dans un système biologique complexe. Cette approche se présente sous la forme d'un modèle formel décrivant le métabolisme d'un organisme vivant, qui grâce au formalisme DEVS (Discret Event System Specification) adopté, permet un couplage avec des modèles d'interaction entre les organismes et entre l'organisme et son environnement. Une étude des différents paradigmes de modélisation, nous a permis d'identifier d'un côté le paradigme adéquat pour chaque niveau et d'un autre côté les facteurs de couplage formés par les variables à l'interface des mondes internes et externes d'un individu. Ce couplage permet d'explorer l'effet de la dynamique du niveau inférieur sur l'émergence des caractéristiques du niveau supérieur. Deux modèles multi-agents, le premier sur l'allocation sexuelle et le deuxième sur la recherche optimale de nourriture, concrétisent le couplage physiologie/écologie et montrent que ce couplage permet de relier le monde interne de l'individu à son monde externe. Le couplage fort, dans le sens de l'intégration des modèles, exploré dans une première phase, a été amélioré par la proposition d'un modèle formel, nommé DEB-DEVS, du modèle métabolique (de la théorie du budget d'énergie dynamique (DEB)) commun aux modèles précédents. Cette proposition est le résultat d'une réflexion sur la représentation de la dynamique interne des agents dans des modèles de l'écologie. DEB-DEVS a été illustré par deux modèles classiques de l'écologie théorique.