Teses / dissertações sobre o tema "Réseaux d'interaction de protéines"
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Souiai, Oussema. "Analyses et prédictions bioinformatiques de réseaux d'interactions protéine-protéines contextualisés". Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX22039.
Texto completo da fonteThis work aims at contextualizing and studying contextualized protein interaction networks. The first topic of my investigations is about predicting and analyzing tissular interactomes. Combined functional and topological analyses were performed. The combination of these features highlighted the existence of a functional core centrally located dedicated to housekeeping functions, central tissue-specific interactions involved in regulatory and developmental functions and peripheral tissue-specific interactions involved in organ physiological functions. This gradient of functions recapitulates the organization of organs, from cells to organs. The second topic of my thesis is the contextualization of macrophage interaction network. To infer the most likely macrophage interactome, we integrated the PPI dataset with other type of meta-data, statistically evaluated them and proposed a macrophage-contextualized interactome. The set of selected interactions is enriched in : experimentally verified interactions and immune related Biological Processes. The functional analysis of such networks brings valuable information on the cellular and molecular mechanisms sustaining the infection
Brouard, Céline. "Inférence de réseaux d'interaction protéine-protéine par apprentissage statistique". Phd thesis, Université d'Evry-Val d'Essonne, 2013. http://tel.archives-ouvertes.fr/tel-00845692.
Texto completo da fonteDiss, Guillaume, e Guillaume Diss. "Architecture et évolution des réseaux d'interactions protéines-protéines : exploration de la carte génotype-phénotype". Doctoral thesis, Université Laval, 2014. http://hdl.handle.net/20.500.11794/25454.
Texto completo da fonteTableau d'honneur de la Faculté des études supérieures et postdorales, 2014-2015
La question des bases structurales du phénotype et de sa variation est une des questions les plus anciennes de la biologie. Le paradigme actuel stipule que le phénotype est exprimé à partir du génotype au travers de réseaux moléculaires dont l’architecture structure l’information génétique. Cette description mécanistique de la carte génotype-phénotype implique que c’est par la perturbation de l’architecture de ces réseaux que des variations génotypiques mènent à des modifications du phénotype. Les protéines constituant le principal vecteur de l’information génétique, comprendre la carte génotype-phénotype requiert de comprendre comment les variations génotypiques perturbent l’architecture du réseau d’interactions protéines-protéines. Au cours de cette thèse, nous avons développé une méthode permettant d’étudier chez la levure Saccharomyces cerevisiae l’impact de la délétion des gènes sur les interactions entre protéines. Nous avons appliqué cette méthode à l’étude des mécanismes moléculaires de la robustesse par lesquels le réseau d’interactions protéines-protéines filtre les variations génotypiques pour préserver le phénotype. Nous avons mis au jour un mécanisme de compensation fonctionnelle entre gènes paralogues basé sur la compensation des interactions protéines-protéines et expliquant un lien entre génotype et phénotype qui était mal compris jusqu’alors. En outre, en appliquant notre méthode à l’identification des régulateurs de la Protéine Kinase A, nous avons approfondi les connaissances sur la façon dont les maîtres régulateurs coordonnent les processus cellulaires et maintiennent l’homéostasie, une propriété distribuée de la robustesse. Ces résultats, et ceux qui seront produits à l’avenir par l’application de cette méthode, promettent une meilleure compréhension des mécanismes moléculaires par lesquels l’information génétique est transmise du génotype au phénotype, condition essentielle à la compréhension du vivant et de son évolution.
La question des bases structurales du phénotype et de sa variation est une des questions les plus anciennes de la biologie. Le paradigme actuel stipule que le phénotype est exprimé à partir du génotype au travers de réseaux moléculaires dont l’architecture structure l’information génétique. Cette description mécanistique de la carte génotype-phénotype implique que c’est par la perturbation de l’architecture de ces réseaux que des variations génotypiques mènent à des modifications du phénotype. Les protéines constituant le principal vecteur de l’information génétique, comprendre la carte génotype-phénotype requiert de comprendre comment les variations génotypiques perturbent l’architecture du réseau d’interactions protéines-protéines. Au cours de cette thèse, nous avons développé une méthode permettant d’étudier chez la levure Saccharomyces cerevisiae l’impact de la délétion des gènes sur les interactions entre protéines. Nous avons appliqué cette méthode à l’étude des mécanismes moléculaires de la robustesse par lesquels le réseau d’interactions protéines-protéines filtre les variations génotypiques pour préserver le phénotype. Nous avons mis au jour un mécanisme de compensation fonctionnelle entre gènes paralogues basé sur la compensation des interactions protéines-protéines et expliquant un lien entre génotype et phénotype qui était mal compris jusqu’alors. En outre, en appliquant notre méthode à l’identification des régulateurs de la Protéine Kinase A, nous avons approfondi les connaissances sur la façon dont les maîtres régulateurs coordonnent les processus cellulaires et maintiennent l’homéostasie, une propriété distribuée de la robustesse. Ces résultats, et ceux qui seront produits à l’avenir par l’application de cette méthode, promettent une meilleure compréhension des mécanismes moléculaires par lesquels l’information génétique est transmise du génotype au phénotype, condition essentielle à la compréhension du vivant et de son évolution.
The question of the structural bases of the phenotype and of its evolution is one of the oldest questions in biology. The present paradigm states that the phenotype is expressed from the genotype through molecular networks, the architecture from which structures genetic information. This mechanistic description of the genotype-phenotype map implies that it is through by perturbing of the architecture of these networks that genotypic variations lead to phenotypic modifications. Since proteins are the main vector of genetic information, understanding the genotype-phenotype map requires the understanding of how genotypic variations perturb the architecture of the protein interaction network. In the course of this thesis, we developped a methodology that allows to study the impact of gene deletions on the interactions between proteins in the yeast Saccharomyces cerevisiae. We applied this method to the study of the molecular mechanisms of robustness by which the protein interaction network filters genotypic variations to preserve the phenotype. We uncovered un mechanism of functional compensation between paralogous genes that is based on protein-protein interaction compensation and that explains the poorly understood link between genotype and phenotype. Moreover, we applied our method to the identification of regulators of Protein Kinase A and deepened our knowledge of how master regulators coordinate cellular processes and maintain homeostasis, a distributed property of robustness. These results, and the ones that will be produced in the future by applying this method, promise a better understanding of the molecular mechanisms through which genetic information is transmitted from the genotype to the phenotype, an essential condition for the understanding of life and its evolution.
The question of the structural bases of the phenotype and of its evolution is one of the oldest questions in biology. The present paradigm states that the phenotype is expressed from the genotype through molecular networks, the architecture from which structures genetic information. This mechanistic description of the genotype-phenotype map implies that it is through by perturbing of the architecture of these networks that genotypic variations lead to phenotypic modifications. Since proteins are the main vector of genetic information, understanding the genotype-phenotype map requires the understanding of how genotypic variations perturb the architecture of the protein interaction network. In the course of this thesis, we developped a methodology that allows to study the impact of gene deletions on the interactions between proteins in the yeast Saccharomyces cerevisiae. We applied this method to the study of the molecular mechanisms of robustness by which the protein interaction network filters genotypic variations to preserve the phenotype. We uncovered un mechanism of functional compensation between paralogous genes that is based on protein-protein interaction compensation and that explains the poorly understood link between genotype and phenotype. Moreover, we applied our method to the identification of regulators of Protein Kinase A and deepened our knowledge of how master regulators coordinate cellular processes and maintain homeostasis, a distributed property of robustness. These results, and the ones that will be produced in the future by applying this method, promise a better understanding of the molecular mechanisms through which genetic information is transmitted from the genotype to the phenotype, an essential condition for the understanding of life and its evolution.
Bertin, Nicolas. "D'une représentation statique à un modèle dynamique des réseaux d'interaction protéine-protéine". Montpellier 2, 2006. http://www.theses.fr/2006MON20124.
Texto completo da fonteTo further understand biological processes, it is important to consider gene functions in the context of complex molecular networks. I joined the lab of Marc Vidal in January 2001, in the midst of its effort to decipher at the scale of the proteome the complex network of protein-protein interactions in the metazoan model organism C. Elegans. To accomplish such a task, one has to first generate a physical resource of coding sequences that can be used in yeast two-hybrid (Y2H) screenings, as well as various other functional assays. In this respect, I participated in the development of a bioinformatics platform facilitating the cloning of 12,000 of the 19,000 predicted Open Reading Frames (ORFs) in C. Elegans (Nature Genetics 2003). This platform was subsequently used in two similar efforts to generate the ORFeome of the pathogen bacteria B. Melitensis (Genome Research 2004a) (96% of the predicted ORFs of B. Melitensis were cloned) and a first version of the human ORFeome containing approximately 8,000 ORFs (Genome Research 2004b). Using the C. Elegans ORFeome resource, a huge team effort led to the generation of one of the first metazoan interactomes, uncovering the network formed by 5,500 protein-protein interactions (Science 2004). My involvement in that project was the development of a bioinformatics pipeline allowing an efficient acquisition of the data generated by the high-throughput Y2H screenings, as well as tools to integrate this dataset with the huge body of transcriptional and phenotypic data available. I have demonstrated that currently known protein-protein interactions cover only a small portion of the full interactomes (Nature Biotechnology 2005). Nevertheless, they can be used as a scaffold on which other functional information can be overlaid to improve our understanding of key biological processes. By creating tools to bring together genetic, transcriptional and functional data into the interactome, I participated in the discovery of new functional links between genes expressed in the germline of C. Elegans (Current Biology 2002), as well as the uncovering of new components involved in the TGF-beta signaling pathway (Molecular Cell 2004), the RNAi machinery (Science 2005) and C. Elegans embryogenesis (Nature 2005). All of these studies generated testable hypotheses that strengthened the implication of those new functional links in each of the biological processes investigated. The integration of functional datasets can also be used to reveal emergent properties of biological networks. Taking advantage of the wealth of proteomic, transcriptional and genetic data available for S. Cerevisiae, I have shown that the genetic robustness of the yeast is linked to the modular and hierarchical nature of the topology of its interactome (Nature 2004 and recent submission PloS Biology). While the static nature of current interactomes can be partially overcome by integrating transcriptome and interactome data in unicellular organisms (Nature 2004 and recent submission to PloS Biology), such approaches remain limited for multicellular organisms such as C. Elegans. To decipher the dynamics of the worm interactome, one has to determine the localizations of the expression of its genes in space and in time. Therefore, I joined a high-throughput genome wide expression localization project. The originality of this project resides in a standardized and high-throughput data acquisition of in vivo gene reporter assays allowing the gathering of both spatial as well as temporal expression patterns for nearly 2,000 C. Elegans promoters. This new biological map, the "localizome", will be used to not only refine the current static interactome and define tissue-specific interactomes, but also to gain a system-level understanding of gene regulation during the post-embryonic development of C. Elegans (under consideration in Nature)
Marois-Blanchet, François-Christophe. "Le rôle de la régulation transcriptionnelle dans l'évolution des réseaux d'interaction protéine-protéine". Thesis, Université Laval, 2011. http://www.theses.ulaval.ca/2011/28445/28445.pdf.
Texto completo da fonteEvolution by gene duplication is considered one of the most important mechanisms of evolutionary innovation. What is less known and highly debated is the relative role of the divergence of transcriptional regulation and the divergence of protein coding sequence in the evolution of molecular networks. We developed a method aimed at evaluating the role of transcriptional regulation in the divergence of protein-protein interactions among duplicated genes in the budding yeast Saccharomyces cerevisiae. Our results demonstrate that our approach can be used effectively to test if divergence of protein-protein interaction profiles can be explained by the divergence of transcriptional regulation or the divergence of coding sequences. We found evidence supporting different scenarios, whereby expression regulation has a large effect, no effect or little effect on protein-protein interaction profiles of paralogous proteins. Our method can be brought to large scale and help elucidate the importance of gene transcriptional regulation in evolution of complex cellular networks.
Chesneau, Alban. "Génération et utilisation d'un réseau d'interaction protéine/protéine : Exemple des protéines de remodelage de la chromatine chez C. elegans". Montpellier 2, 2005. http://www.theses.fr/2005MON20029.
Texto completo da fonteBaussand, Julie. "Evolution des séquences protéiques : signatures structurales hydrophobes et réseaux d'acides aminés co-évolués". Paris 6, 2008. http://www.theses.fr/2008PA066011.
Texto completo da fontePeysselon, Franck. "Désordre intrinsèque et analyses de réseaux d'interactions extracellulaires : des protéines et polysaccharides aux interactions hôte-Leishmania". Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10317.
Texto completo da fonteBiomolecules perform their functions by interacting with other molecules. The identification of all biomolecules and their interactions is required to build their interaction networks. Their structural and functional analysis with bioinformatics tools (BiNGO, DAVID) allow us to identify the key biomolecules, to predict new protein functions and to understand and model the molecular mechanisms of biological or pathological process. Intrinsically disordered proteins or regions, which are characterized by structural plasticity, may interact with many partners and may play a role in the interaction networks. Using the predictor IUPred we mapped the intrinsic disorder in protein interaction networks of the extracellular matrix and of the proteoglycans constructed from the MatrixDB database developed in the laboratory. We have shown that the highest connected proteins of these two networks are not enriched in disorder. The molecular functions overrepresented in the set of extracellular proteins containing at least 50% of intrinsically disordered residues are interactions with growth factors or glycosaminoglycans. We studied a dataset of heparin-protein interactions including 118 kinetic values and we have shown that the association rate of proteins with heparin is related to the intrinsic disorder of heparin-binding sites. We also studied the interactions of the extracellular matrix with a pathogen, the parasite Leishmania. We have shown that proteins secreted by Leishmania are not enriched in disorder compared to their proteome. We have selected eleven parasite proteins containing at least three interaction motifs, which may interact with the host
Tiouajni, Mounira. "Caractérisation structurale et fonctionnelle du réseau d'interaction du Gelatin Binding Domain de la fibronectine humaine". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114820.
Texto completo da fonteThe extracellular matrix (ECM) is involved in a number of biological pathways associated with the cell migration, differentiation, adhesion and is also implicated in several pathological events. The cohesion of the ECM is accomplished by a highly organized protein complex network on the cell surface. The Gelatin Binding Domain (GBD) (⁶FI¹²FII ⁷⁸⁹FI) of the N-terminal region of fibronectin is found to interact with the transglutaminase 2 (TG2), collagen type I and the bacterial adhesion protein FNE. In this study, we conducted the structural and functional characterization of the protein complexes involved in the cohesion of ECM. The interactions between either TG2 or FNE and GBD have been characterized and the regions responsible for the interactions have also been mapped. Furthermore, we studied TG2/GBD and FNE/GBD complex by SAXS and built two models underscoring the interactions between (1), the GBD and the Nterminus of TG2 and (2), FNE and the sub-fragment ⁷⁸⁹FI of GBD providing insights on mechanistically elucidating the protein interactions during the cohehsion of ECM. The X-ray structure of the protein FNE of Streptococcus equi has been determined at 1.8 Å, by using an original tool that facilitates obtaining crystals
Brohée, Sylvain. "Etude bioinformatique du réseau d'interactions entre protéines de transport ches les Fungi". Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210432.
Texto completo da fonteL'objectif global de notre travail consiste à combler ces lacunes et à préciser les interactions entre protéines membranaires chez la levure Saccharomyces cerevisiae et plus précisément, entre les transporteurs. Nous avons commencé notre travail par l'étude d'un jeu de données d'interactions à grande échelle entre toutes les perméases détectées par une méthode de double hybride spécialement adaptée aux protéines insolubles (split ubiquitin). Premièrement, la qualité des données a été estimée en étudiant le comportement global des données et des témoins négatifs et positifs. Les données ont ensuite été standardisées et filtrées de façon à ne conserver que les plus significatives. Ces interactions ont ensuite été étudiées en les modélisant dans un réseau d'interactions que nous avons étudié par des techniques issues de la théorie des graphes. Après une évaluation systématique de différentes méthodes de clustering, nous avons notamment recherché au sein du réseau des groupes de protéines densément interconnectées et de fonctions similaires qui correspondraient éventuellement à des complexes protéiques. Les résultats révélés par l'étude du réseau expérimental se sont révélés assez décevants. En effet, même si nous avons pu retrouver certaines interactions déjà décrites, un bon nombre des interactions filtrées semblait n'avoir aucune réalité biologique et nous n'avons pu retrouver que très peu de modules de protéines de fonction semblable hautement inter-connectées. Parmi ceux-ci, il est apparu que les transporteurs d'acides aminés semblaient interagir entre eux.
L'approche expérimentale n'ayant eu que peu de succès, nous l'avons contournée en utilisant des méthodes de génomique comparative d'inférence d'interactions fonctionnelles. Dans un premier temps, malgré une évaluation rigoureuse, l'étude des profils phylogénétiques (la prédiction d'interactions fonctionnelles en étudiant la corrééélation des profils de présence - absence des gènes dans un ensemble de génomes), n'a produit que des résultats mitigés car les perméases semblent très peu conservées dès lors que l'on considère d'autres organismes que les \
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Iragne, Florian. "Prédiction de réseaux d'interactions biomoléculaires à partir de données de la génomique comparée". Phd thesis, Université Sciences et Technologies - Bordeaux I, 2007. http://tel.archives-ouvertes.fr/tel-00409871.
Texto completo da fonteMohseni, Behbahani Yasser. "New computational approaches to study the effect of genetic mutations on the topology of protein-protein interaction networks". Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS257.pdf.
Texto completo da fonteWith the recent advances in protein structure prediction, protein-protein interactions (PPI) are becoming more central than ever. Reliable predictions of who the cognate partners are and how they interact, as well as how missense mutations affect these interactions, have enormous implications for medicine. This thesis focuses on two aspects of PPI. First, the current knowledge of PPI relies on partial, noisy and heterogeneous data. To address this problem, we developed a reliable, versatile and interactive web-based tool, called LEVELNET, for visualising, exploring and comparing PPI networks toward biological interpretation. It breaks down the complexity of PPI networks by representing them as multi-layered graphs inferred from different sources. Second, we introduced a novel computational framework based on geometric deep learning, called Deep Local Analysis (DLA), that represents a protein interface as an ensemble of locally oriented residue-centred cubes describing a residue and its atomic environment. It is invariant to the global orientation of the structure while fully accounting for the relative orientation of an interfacial residue with respect to its neighboring atoms. We also built a structure-based general-purpose encoder generating informative representations from local interfacial environments that can be used in various downstream tasks. We challenged DLA on two fundamental questions about PPI: (i) identification of near-native protein complex conformations, and (ii) prediction of the effects of mutations on protein interactions. Beyond achieving the state-of-the-art predictive power in its objectives, DLA is shown useful for multiple applications. The local cubes are found to be the minimum unit of information at the interface necessary to predict both the quality of interactions and the effect of mutations
Carvunis, Anne-ruxandra. "Des protéines et de leurs interactions aux principes évolutifs des systèmes biologiques". Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00586614.
Texto completo da fonteRochette, Samuel. "Utilisation de pertubations environnementales et génétiques du réseau d'interactions protéine-protéine pour disséquer des processus cellulaires". Master's thesis, Université Laval, 2014. http://hdl.handle.net/20.500.11794/25483.
Texto completo da fonteProteins are the molecular machines allowing the cell to accomplish a myriad of biological functions. To do so, proteins physically interact with each other in a reversible and tunable way, providing the cell a mechanism to quickly adapt to a changing environment. Thus, studying the dynamics of protein-protein interactions is key in understanding how cells adapt to various perturbations. The chapters included in this thesis illustrate the development of a method to identify and quantify changes in protein-protein interactions in response to environmental perturbations and how protein-protein interactions can be used as reporters to dissect the regulatory network of a protein phosphatase, calcineurin, using a network perturbation approach. Together, these two chapters illustrate the utility of network perturbation approaches to dissect complex cellular processes.
Ribeiro, Diogo. "Discovery of the role of protein-RNA interactions in protein multifunctionality and cellular complexity". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0449/document.
Texto completo da fonteOver time, life has evolved to produce remarkably complex organisms. To cope with this complexity, organisms have evolved a plethora of regulatory mechanisms. For instance, thousands of long non-coding RNAs (lncRNAs) are transcribed by mammalian genomes, presumably expanding their regulatory capacity. An emerging concept is that lncRNAs can serve as protein scaffolds, bringing proteins in proximity, but the prevalence of this mechanism is yet to be demonstrated. In addition, for every messenger RNA encoding a protein, regulatory 3’ untranslated regions (3’UTRs) are also present. Recently, 3’UTRs were shown to form protein complexes during translation, affecting the function of the protein under synthesis. However, the extent and importance of these 3’UTR-protein complexes in cells remains to be assessed.This thesis aims to systematically discover and provide insights into two ill-known regulatory mechanisms involving the non-coding portion of the human transcriptome. Concretely, the assembly of protein complexes promoted by lncRNAs and 3’UTRs is investigated using large-scale datasets of protein-protein and protein-RNA interactions. This enabled to (i) predict hundreds of lncRNAs as possible scaffolding molecules for more than half of the known protein complexes, as well as (ii) infer more than a thousand distinct 3’UTR-protein complexes, including cases likely to post-translationally regulate moonlighting proteins, proteins that perform multiple unrelated functions. These results indicate that a high proportion of lncRNAs and 3’UTRs may be employed in regulating protein function, potentially playing a role both as regulators and as components of complexity
Lippi, Sylvain. "Théorie et pratique des réseaux d'interaction". Aix-Marseille 2, 2001. http://www.theses.fr/2002AIX22012.
Texto completo da fonteBerger, Caroline, e Caroline Berger. "Étude du dynamisme et de l'évolution des réseaux d'interactions protéiques par une approche de protéomique comparative". Master's thesis, Université Laval, 2020. http://hdl.handle.net/20.500.11794/38219.
Texto completo da fonteUn objectif fondamental de la biologie évolutive est de comprendre comment l’information contenue dans le génotype peut être transmise au phénotype. Les hybrides, issus du croisement entre deux espèces différentes, représentent une opportunité unique d’explorer le lien qui existe entre génotype et phénotype. L’hybridation peut mener à la mise en place de phénotypes extrêmes (tels que l’hétérosis ou la sous-dominance) et beaucoup d’études s’intéressent aux bases génétiques de ces phénotypes. Pourtant, il y a une véritable lacune dans notre compréhension du lien entre génotype et phénotype chez les hybrides. Notre hypothèse était que ce lien se fait par l’intermédiaire des complexes protéiques et que l’hybridation devrait induire une réorganisation des complexes. Pour tester cette hypothèse, nous avons utilisé une méthode d’étude des complexes protéiques (SEC-PCP-SILAC) qui permet de cibler un grand nombre de complexes dans la cellule. Des hybrides de levures ont été générés au laboratoire et SEC-PCP-SILAC a été utilisé pour comparer les complexes protéiques des hybrides par rapport aux complexes parentaux. Nous avons été en mesure de capturer une large fraction de l’interactome avec la détection de 39% des complexes protéiques présents chez la levure. Nos résultats mettent en évidence la robustesse générale des complexes protéiques après hybridation. Toutefois, des modifications non négligeables du réseau d’interactions ont aussi été détectées. Ces modifications affectent deux voies biologiques majeures : la voie de synthèse du glucose et la voie liée à l’activité ribosomale. Ce sont des voies candidates intéressantes pour expliquer la différence de phénotype qui peut exister entre parents et hybrides. Finalement, l’utilisation d’une méthode alternative, la PCA, a permis de complémenter les données de spectrométrie de masse, en démontrant notamment la présence d’interactions parentales (intra-espèces) et chimériques (inter-espèces) chez les hybrides. Ce mémoire souligne ainsi l’importance d’adopter une approche intégrative pour une meilleure compréhension du lien génotype-phénotype.
A fundamental goal in evolutionary biology is to understand how the information contains in the genotype can be transmitted to the phenotype. Hybrids, that are the result of the cross between different species, represent a unique opportunity to investigate the link between genotype and phenotype. Hybridization can lead to extreme phenotypes (such as heterosis or underdominance) and many studies try to understand the genetic bases of these phenotypes. However, there is a real gap in our understanding of the link between genotype and phenotype in hybrids. Our hypothesis was that protein complexes would play a key role and that hybridization would lead to changes in the organisation of protein complexes. To test this hypothesis, we used a method (SEC-PCP-SILAC) that allows studying broadly protein complexes in the cell. Hybrids between yeast species were generated in the laboratory and SEC-PCP-SILAC was applied to compare the protein complexes of the hybrids with their parental species. We were able to detect a large fraction of the interactome with the identification of 39% of the protein complexes reported in yeast. Our results highlight the general robustness of the protein complexes after hybridization. However, some significant changes of the interaction networks were also detected in hybrids. These modifications involve two main biological pathways: the glucose synthesis pathway and the ribosomal activity pathway. They are promising candidates to explain the phenotypic differences between hybrids and parents. Finally, a complementary PCA approach was used to complement the mass-spectrometry data and we demonstrated the presence of both parental (within species) and chimeric (between species) interactions. This thesis emphasizes the importance to use an integrative approach for a better understanding of the link between genotype and phenotype.
A fundamental goal in evolutionary biology is to understand how the information contains in the genotype can be transmitted to the phenotype. Hybrids, that are the result of the cross between different species, represent a unique opportunity to investigate the link between genotype and phenotype. Hybridization can lead to extreme phenotypes (such as heterosis or underdominance) and many studies try to understand the genetic bases of these phenotypes. However, there is a real gap in our understanding of the link between genotype and phenotype in hybrids. Our hypothesis was that protein complexes would play a key role and that hybridization would lead to changes in the organisation of protein complexes. To test this hypothesis, we used a method (SEC-PCP-SILAC) that allows studying broadly protein complexes in the cell. Hybrids between yeast species were generated in the laboratory and SEC-PCP-SILAC was applied to compare the protein complexes of the hybrids with their parental species. We were able to detect a large fraction of the interactome with the identification of 39% of the protein complexes reported in yeast. Our results highlight the general robustness of the protein complexes after hybridization. However, some significant changes of the interaction networks were also detected in hybrids. These modifications involve two main biological pathways: the glucose synthesis pathway and the ribosomal activity pathway. They are promising candidates to explain the phenotypic differences between hybrids and parents. Finally, a complementary PCA approach was used to complement the mass-spectrometry data and we demonstrated the presence of both parental (within species) and chimeric (between species) interactions. This thesis emphasizes the importance to use an integrative approach for a better understanding of the link between genotype and phenotype.
Chaintreau, Augustin. "Processus d'interaction dans les réseaux de données". Paris 6, 2006. http://www.theses.fr/2006PA066601.
Texto completo da fonteSaravanamuthu, Gunalini. "Détermination des sites d'interaction des protéines par spectrométrie de masse MALDI-TOF". Paris 6, 2011. http://www.theses.fr/2011PA066730.
Texto completo da fonteVelázquez-Godínez, Erick. "Des techniques d'interaction bimanuelles pour la manipulation de visualisations de réseaux". Mémoire, École de technologie supérieure, 2012. http://espace.etsmtl.ca/973/1/VELAZQUEZ%2DGODINEZ_Erick.pdf.
Texto completo da fonteDe, Falco Marc. "Géométrie de l'Interaction et Réseaux Différentiels". Phd thesis, Université de la Méditerranée - Aix-Marseille II, 2009. http://tel.archives-ouvertes.fr/tel-00392242.
Texto completo da fonteDans un premier temps, on présente les réseaux d'interaction de Lafont comme une instance particulière de GdI. Puis, on définis un cadre général d'étude de la GdI à partir d'un ensemble de symboles et de règles d'interaction.
Dans un second temps, on introduit une notion de concision associée à la GdI et on montre dans quelle mesure cette notion fait du sens à l'aide d'une famille d'exemple basée sur les entiers de Church.
Dans un dernier temps, on présente les réseaux d'interaction différentiels d'Ehrhard et Regnier et on définit leur GdI. On montre que la théorie usuelle de Danos-Regnier est entièrement récupérée.
Elqaidi, Samir. "Etude de la spécificité d'interaction des protéines homologues Mlc et NagC avec l'ADN". Paris 6, 2008. http://www.theses.fr/2008PA066434.
Texto completo da fonteBaslé, Emmanuel. "Détection d'interaction avec les protéines : synthèse de sondes polyfonctionnelles et application aux polyamines". Rennes 1, 2010. http://www.theses.fr/2010REN1S105.
Texto completo da fonteChemical Biology defines a domain focused on the development of chemical tools for biology. Among this domain, our interests were directed toward two important areas: endogenous protein chemical modification and polyfunctional probes synthesis. This work was especially focused on the biology of polyamines. Its originality lies in the combination of methodology and multi-step synthesis. We first developped a copper catalyzed reaction for nitrogen heterocycles N-arylation. After optimization of reaction conditions, it was applied to endogenous protein chemical modification. Then bifunctional and trifunctional probes, derived from polyamines, have been synthesized. These molecules have fluorescent, affinity or photo-activatable moieties. They subsequently have been tested on different biological systems
Begue, Hervé. "Etude du rôle de la protéine CDC48 dans l'immunité des plantes". Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCK037/document.
Texto completo da fonteThe chaperone protein CDC48 (Cell division cycle 48) is a major regulator of the quality control of proteins and is involved in various cellular processes in animals and yeast. In contrast, the role of CDC48 in plants is poorly known. In the present work, we investigated the function of CDC48 in plant immunity thanks to the cryptogein/tobacco biological model, cryptogein being produced by the oomycete phytophthora cryptogea.Three strategies were carried out. First, the dynamic of accumulation CDC48 together with intracellular events inherent to the immune response were analyzed in both wild-type and CDC48 overexpressing tobacco cells (CDC48-TAP line). Second, a list if CDC48 partners was established based on immunoprecipitation assays followed by mass spectroscopy analysis. Among those partners the cytosolic form of acorbate peroxidase (cAPX), a central enzyme of the regulation of the redox status regulation, has been specifically studied. Finally, a computational analysis of the partner list of CDC48 and the subsequent generation of the protein-protein interaction (PPI) network of CDC48 in Arabidopsis thaliana were undertook.Our data indicated that the activation of the immune response is accompanied by an induction of the accumulation of both CDC48 transcript and protein. In addition, an early and exacerbated cell death was observed in the CDC48-TAP line, suggesting a role for CDC48 in the hypersensitive response. The interaction between CDC48 and cAPX was confirmed by different approaches. Interestingly, the activity of CDC48 and its dynamic of accumulation were strongly impacted in the CDC48 overexpressing line. Accordingly, a dysregulation of the redox status also occurred in this line. Finally, the computational analysis of the CDC48 PPI network highlighted new potential target proteins including proteins involved in the metabolism of S-adenosylmethionine, a substrate molecule of trans-methylation reactions and precursor of ethylene and nicotianamine.To summarize, this work provides new information about CDC48 in plant biology. It indicates that CDC48 is mobilized by plant cells undergoing an immune response and impacts the redox status through the regulation of the cAPX turnover. New research avenues emerged from our study, notably a putative role of CDC48 in the regulation of S-adenosylmethionine biosynthesis and in the establishment of hypersensitive response through process which remain to be investigated
Mazouzi, Hamza. "Ingénierie des protocoles d'interaction : des systèmes distribués aux systèmes multi-agents". Paris 9, 2001. https://portail.bu.dauphine.fr/fileviewer/index.php?doc=2001PA090041.
Texto completo da fonteGallaud, Julien. "Etude des réseaux d'interactions protéiques impliqués dans le trafic du nickel et de l'ammoniac et de leurs rôles dans la virulence chez Helicobacter pylori". Paris 7, 2012. http://www.theses.fr/2012PA077093.
Texto completo da fonteTo withstand stress encountered in its niche, H. Pylori (Hp) got an emergency response that depends on ammonia production by urease, an abundant and very active nickel metalloenzyme. Another enzyme essential for colonization, the hydrogenase, needs nickel too for its catalytic centers. That is why nickel is an essential micronutrient for Hp. To survive, Hp has to import nickel and then insert it correctly in these two enzymes. Moreover, this metal should be stored to avoid the deleterious effects it may cause. We studied the role of two histidine-rich protein, Hpn and Hpn-2. We have shown that these proteins are essential for colonization, interact with each other, are involved in the nickel homeostasis and storage of nickel and act as regulators of urease activity. We have characterized two periplasmic Systems of hydrolysis of asparagine and glutamine associated with ammonia production. These enzymes are coupled to an import of aspartate and glutamate in the cell. These Systems are critical to colonization and play a role in the pathogenicity of Hp. Using the bacterial two-hybrid, the interactions between ammonia-producing enzymes and enzymes that use it as substrate have been identified. We propose the existence of metabolic channeling of ammonia to optimize the bioavailability of this molecule and the corresponding enzymes activity. Our results revealed the existence of protein interactions that optimize the flow of ammonia and nickel and are essential for the virulence of Hp
Khalil, Lionel. "Généralisation des réseaux d'interaction avec l'agent amb de Mc Carthy : propriétés et applications". Palaiseau, Ecole polytechnique, 2003. http://www.theses.fr/2003EPXX0015.
Texto completo da fonteHuget, Marc-Philippe. "Une Ingénierie des protocoles d'interaction pour les systèmes multi-agents". Paris 9, 2001. https://portail.bu.dauphine.fr/fileviewer/index.php?doc=2001PA090015.
Texto completo da fontePécot, Jessie. "Dépendance des cellules cancéreuses à BCL-xL : ciblage thérapeutique du réseau d'interactions PUMA, BAX et BCL-xL : effets oncogéniques non canoniques de l'interaction RAS / BCL-xL". Nantes, 2015. https://archive.bu.univ-nantes.fr/pollux/show/show?id=57dfe09c-18e6-4d60-a1e1-cbc567f5cda6.
Texto completo da fonteBCL-xL plays a role in chemoresistance that needs to be overcome. We show here that currently available BH3-mimetics do not efficiently derepress BCL-xL inhibition of BAX-mediated cell death induced by PUMA, a major pro-apoptotic effector of chemotherapy. Live cell measurements of protein-protein interactions reveal that BH3-mimetics readily inhibit BAX interactions with BCL-xL and the effects of BCL-xL on BAX oligomerization but that PUMA interactions with BCL-xL are highly resistant. Thus, PUMA only favors BAX oligomerization/activation and induction of cell death in response to BH3-mimetics when BCL-xL expression is limiting. Mutagenesis studies show that the robustness of PUMA/BCL-xL interactions is due to the avidity of the PUMA BH3 domain for mitochondrial BCL-xL. This has important consequences for the design of strategies combining PUMA-inducing genotoxics and BCL-xL inhibitors, and argues that mitochondrial membranes per se influence treatment outcome. BCL-xL does not only function as guardian of mitochondrial permeability. Non-canonical effects and functions of this protein have been described, as its interaction with the RAS oncogene. Some studies suggest the oncogenic effects of the BCL-xL/RAS interaction. However, its functional consequences remain unknown. So we have used BRET and pep-scan assays in order to structurally and functionally characterize this interaction
Pozza, Alexandre. "Surexpression hétérologue et purification du transporteur membranaire ABCG2 : mécanisme d'interaction avec des substrats et des inhibiteurs spécifiques". Lyon 1, 2007. http://www.theses.fr/2007LYO10327.
Texto completo da fonteABCG2 is an ABC half-transporter involved in multidrug resistance of cancer cells. Our aim is to understand the mechanism of transport and of interaction with specific inhibitors. After some unsuccessful attempts in bacteria, ABCG2 was functionally overexpressed with the insect cells/baculovirus system. The effects of some inhibitors on ATPase activity were studied, as well as the capacity of binding to the purified transporter. This allowed to bring evidence for a different inhibition mechanism for the same inhibitor between the wild-type and R482T mutant of the transporter. The difference in transport-substrate spectrum induced by the mutation is not due to binding, but more likely related to membrane translocation. The recombinant protein appears as two bands, the difference of which is probably of conformational origin
Jean-Alphonse, Frédéric. "Récepteur V2 de la vasopressine : à la recherche de partenaires d'interaction et d'outils thérapeutiques". Montpellier 1, 2008. http://www.theses.fr/2008MON13514.
Texto completo da fonteAstier, Catherine. "Caractérisation des propriétés d'interaction de la titine, protéine musculaire géante, et stabilité des structures sarcomériques". Montpellier 1, 1993. http://www.theses.fr/1993MON1T033.
Texto completo da fonteZenou, Benoît Pierre Léon. "Le capital social comme un potentiel d'interaction coopérative : Le cas des relations intergénérationnelles familiales". Montpellier 1, 2009. http://www.theses.fr/2009MON10040.
Texto completo da fonteFrom tools and approaches of different disciplines, we propose an economic study of individual social capital to reveal the economic and behavioral stakes of the introduction of the concept in economic models. We define it as an interactionnal cooperative potential, ie a set of resources which enables agents to access the resources of their partners. From an investigation of the description of the link, we show that it is a form of capital since it is subject to an accumulation, a production and a depreciation. It enables or facilitates interpersonal resources' transfers including reducing transaction costs which involved. We also show that it can be a transfer in mediatized relationship resource and particularly in the case of intergenerational relationships into families. Descendant transfers of parental social capital to child and the stock of initial social capital available to it at its birth, enables accumulate more social capital and unrelate to have some socioeconomic benefits. By transferring their own social capital, parents ensure the well being of their children and accumulate related debts, which they can mobilize at the end of their life to benefit from ascendant intergenerational "transfers of time". Our investigation must be understood as a tool to comprehend what happens in a relationship between two agents and the exchanges they allow. Applied to intergenerational relations, we are laying the ties and conceptualization of social capital as a tool to understand relations, transfers and heritage of the agent
Passot, Fanny. "Rôle et spécificité d'interaction des systèmes parABS de Burkholderia cenocepacia, bactérie multi-chromosomique". Toulouse 3, 2011. http://thesesups.ups-tlse.fr/1384/.
Texto completo da fonteWe are working on B. Cenocepacia J2315 (Bcen), which genome is divided into 3 chromosomes (c1, c2, c3) and 1 plasmid (pBC), each carrying a parABS system, homologs of known plasmid segregation systems. By studying deletions of the parAB operons and excess of parS sites, I proved that parABS systems are important for fitness. More specifically, the analysis of the replicon origin localizations indicates that these systems are implied in the segregation of their own replicons. To avoid incompatibility, the 4 parABS systems must avoid cross-interactions. This is achieved by a stringent ParB-parS interaction, as shown by lack of recognition of mutant parSc1 or parSc3 in toxicity tests in Bcen. Identification and analysis of a group of related parABS, exclusive of the secondary replicons of the Burkholderiales, allowed us to identify a pHTH domain implied in ParB binding on parS, and to reveal that compatibility drives a diversifying evolution of the parABS systems
Clerici, Marcello. "Etudes structurales du mécanisme d'interaction des protéines UPF1 et UPF2, impliquées dans le "Nonsense Mediated mRNA Decay"". Université Joseph Fourier (Grenoble), 2009. http://www.theses.fr/2009GRE10004.
Texto completo da fonteNonsense-mediated mRNA decay (NMD) is one of the best-characterized rnRNA control mechanisms, which recognise and mediate the degradation oftranscripts containing premature termination codons (PTCs). The data presented in this thesis covers two main aspects of the structural organisation ofUPFI and UPF2 essential NMD proteins: the UPFI-UPF: interaction and its influence on UPFI conformation, and the organisation of the three UPF2 MIF4G domains with insighl on their function. Structures ofthe combined CH (Cysteine/Histidine-rich) and helicase domains ofUPFI in complex with the C-terminal region ofhuman UPF2 provide the first information on both the relative arrangement of the two UPFI domains and the structural basis for the interaction between UPFI and UPF2. Ln the presence of UPF2 the UPFI CH-domain has a fixed orientation with respect to the helicase domain which is maintained by a small interface involvin¬specifie contacts of conserved residues. Ln this orientation, the CH-domain is unlikely to interfere with the helicase function. UPF2 MIF4G-I is a common MIF4G domain with high structural similarity to other known MIF4G domains, despite low sequence identity. Mapping sequence conservation on the solvent exposed surface reveals a phylogenetically conserved patch of the protein, carrying residues putatively involved in RNA binding and a predicted phosphorylation site
Poisson, Ariane. "Etude des fonctions de la Menin, oncosuppresseur impliqué dans les Néoplasies endocriniennes multiples de type 1 : analyse du réseau d'interactions protéiques et identification de nouveaux partenaires". Nice, 2005. http://www.theses.fr/2005NICE4003.
Texto completo da fonteStorez, Hélène. "Identification de nouveaux partenaires d'interaction des β-arrestines : 1-oligomérisation des β-arrestines : 2-Caractérisation de l'intéraction β-arrestine- Filamine A". Paris 7, 2007. http://www.theses.fr/2007PA077098.
Texto completo da fonteβ-arrestins 1 and 2 (BARRIand I3ARR2) are two highly homologous proteins with multiple biological functions. First known as key regulators of G protein-coupled receptor (GPCR) desensitization and endocytosis, βARRs were shown more recently to act as scaffolding proteins for ERK1/2 and JNK3 cascades, to activate Src and to bind to ubiquitin ligases. In addition to their propensity to interact with multiple partners, βARRs might also auto-assemble to form oligomers, as suggested by the observation that both IJARR1 and visual arrestin, the isoform which is specifically expressed in the retina, form dimers in crystals. In a two-hybrid screen, based on the Sos Recruitment System and using a C-terminal truncated mutant of βARR2 as the bait, one of the preys corresponded to the C-terminal portion of βARR2 itself, suggesting that βARR2 might also form dimers in solution. To investigate whether βARR2 might function as a dimer in a more physiological context, we took advantage of the bioluminescence energy transfer (BRET) approach, which was developed recently to study protein-protein interaction in living cells. The cDNAs encoding Renilla luciferase (lue) and the yellow variant of the Green Fluorescent Protein (YFP), the BRET donor and accepter moieties, respectively, were fused 5' or 3' to the cDNAs of βARR1 or βARR2. Various appropriate combinations of the resulting constructs were transfected in COS-7 cells. A constitutive BRET was measured with βARR2 constructs. As expected for a specific non-random interaction between the BRET donor and accepter, BRET signals increased as a function of the BRET accepter concentration up to a maximal value (BRETmax), and constant BRET signals were measured when cells were transfected with increasing amounts of a fixed ratio of acceptordonor. Interestingly, significantly different BRETmax values were measured when the BRET donor construct (βARR2-luc) was co-expressed with fusion proteins in which the BRET accepter was located either at the N-terminal (YFP-βARR2) or the C-terminal (βARR2-YFP) extremity of βARR2, indicating that the βARR-2 dimer is oriented. A similar constitutive BRET was also measured for βARR1 and when the BRET donor and the accepter were fused to different UARRisoforms. These data are consistent with a model in which both βARR2 and βARR1 form constitutive homo-dimers in living cells and might also be engaged in constitutive hetero-dimers. Several important questions are still under investigation, such as the proportion of dimers versus monomers, the effect of GPCR activation on βARR dimerization, the potentially different biological function of monomers, homo-dimers and hetero-dimers
Voitovich, Iuliia. "Les inhibiteurs d'interaction protéine-protéine, une stratégie innovante en cancérologie". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0701.
Texto completo da fonteBET-proteins, acting as epigenetic readers, play an essential role in cancer development. To date, numerous potent inhibitors disrupting BET functions have been discovered, including several of them that are undergoing clinical trials for the treatment of different types of cancer. The common drawback limiting their use in clinical practice is an inability to distinguish between BET-members that may cause side effects and resistances. The selective targeting of individual BET and the discrimination between BD1 and BD2 present an opportunity to achieve more selective transcriptional effect. A midthroughput screening of previously designed chemical library allowed identification of two molecules with unique profiles of selectivity that have never been observed. An undertaken structure-based program revealed a minimum scaffolds necessary for binding. Taking together with resolved X-Ray structures it allowed the development of more potent and selective BET inhibitors by DOTS (diversity oriented target focused synthesis) strategy, combining virtual screening and diversity oriented library design. This optimization led to a potent inhibitor with up to 100-fold improvement of affinity to the target and up to 300-fold selectivity toward BD1. Dose-response downregulation of c-Myc levels in low micromolar range in cell assays allowed the validation of the identified molecule as a chemical probe. Further comprehensive in vitro and in vivo evaluations of this compound will enable elucidating the biological role of each bromodomain and a validation of the interest toward the development of selective inhibitors in clinic
Salmon, Valérie. "Production de la lactoferrine humaine par différents systèmes d'expression : applications à l'étude de son site d'interaction avec des cibles moléculaires". Lille 1, 1997. http://www.theses.fr/1997LIL10186.
Texto completo da fonteCorbel, Caroline. "Recherche de nouveaux agents anticancéreux agissant par inhibition d'interaction protéine/protéine : caractérisation de leurs effets cellulaire". Rennes 1, 2011. http://www.theses.fr/2011REN1S024.
Texto completo da fonteMisregulations of CDK5/p25 are implicated in neuronal diseases, as well as in the migration and the metastatic potential of cancer cells. Inhibitors of the CDK5/p25 complex, acting mainly via the ATP pocket of the kinase, have been described. However, this class of inhibitors is subjected to a selectivity problem because a lot of cellular proteins need ATP. We used the BRET (Bioluminescence Resonance Energy Transfer) method to discover new inhibitors of CDK5/p25 interaction. The originality of the assay developed lies in the cellular system used: the yeast Saccharomyces cerevisiae. Following the validation of the method developed, 5571 compounds have been screened. Three molecules were characterized and two of them were mainly studied, notably to understand their mode of inhibition, different from the ATP mimetic compounds
Gavarini, Sophie. "Protéines à domaines PDZ et récepteurs 5-HT2 de la sérotonine : spécificité d'interaction et rôle dans la signalisation". Montpellier 1, 2006. http://www.theses.fr/2006MON1T008.
Texto completo da fonteBénech, Dominique. "Infrastructures d'interaction pour les paradigmes distribués et coopératifs de la gestion intelligente de systèmes et de réseaux". Toulouse 3, 1999. http://www.theses.fr/1999TOU30149.
Texto completo da fonteL'Hoste, Sébastien. "Etablissement d'une carte d'interactions protéiques des petites GTPases Ras et Rap chez l'Homme et la Drosophile par technique de double-hybride : validation génétique des interactions Ras1/CG8965 et Ras1/D-EPAC chez Drosophila melanogaster". Paris 7, 2004. http://www.theses.fr/2004PA077117.
Texto completo da fonteLagnier, Cédric. "Diffusion de l'information dans les réseaux sociaux". Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENM072/document.
Texto completo da fontePredicting the diffusion of information in social networks is a key problem for applications like Opinion Leader Detection, Buzz Detection or Viral Marketing. Many recent diffusion models are direct extensions of the Cascade and Threshold models, initially proposed for epidemiology and social studies. In such models, the diffusion process is based on the dynamics of interactions between neighbor nodes in the network (the social pressure), and largely ignores important dimensions as the content diffused and the active/passive role users tend to have in social networks. We propose here a new family of models that aims at predicting how a content diffuses in a network by making use of additional dimensions : the content diffused, user's profile and willingness to diffuse. In particular, we show how to integrate these dimensions into simple feature functions, and propose a probabilistic modeling to account for the diffusion process. These models are then illustrated and compared with other approaches on two blog datasets. The experimental results obtained on these datasets show that taking into account these dimensions are important to accurately model the diffusion process. Lastly, we study the influence maximization problem with these models and prove that it is NP-hard, prior to propose an adaptation of the greedy algorithm to approximate the optimal solution
Raux, Brigitt. "Développement d'inhibiteurs d'interaction protéine-protéine ciblant les protéines à bromodomaines : implications en épigénétique et dans le développement de cancers". Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0521.
Texto completo da fonteBromodomain-containing proteins (BCPs) are especially involved in the regulation of gene transcription and cell signalling. Their dysregulation lead to the development of pathologies, such as inflammatory, cardiovascular diseases, and more particularly cancers. BCPs involved in the recognition of acetylated lysine of the histone tails, through their BromoDomain(s) module(s) (BDs). Among the eight families of BCPs, my thesis project focuses on the “BET” family. This family comprises four proteins which are composed of a tandem of two BDs each belonging to the BD1 or the BD2 subfamily. The architecture of the central cavity of the BDs, qualified as "druggable", allows the emergence of these proteins as new promising epigenetic targets. To date, about twenty clinical trials targeting different types of cancer have been initiated for "pan-BET" molecules that target all the members of this family. However, "pan-BET" inhibition is clinically problematic because it impacts many transcriptional pathways and causes the appearance of resistant cells. My thesis project is part of the current challenge is to develop more selective inhibitors, for example towards the BET-BD1 subfamily or the BET-BD2 subfamily or ideally towards one single BD inside the BET family. The development of such "selective epigenetic probes" targeting BET family BDs should allow deciphering their role and mechanism of action in various biological processes. Identifying "drug candidates" should lead to new targeted therapies and overcome the resistances related to the use of pan-BET molecules
Boizard, Franck. "Application de la biologie des systèmes pour l'identification de marqueurs moléculaires des maladies rénales dans les fluides biologiques". Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30157.
Texto completo da fonteKidney disease affects about 5 million people in France mostly due to the increase in life expectancy and the evolution of our lifestyles (sedentary living, diet). Patient management is currently largely ineffective due to late diagnosis and our lack of understanding of the complex mechanisms that govern its progression. The study of the urinary proteome has emerged as an excellent way to discover biomarkers of nephropathies and thus to better understand the underlying pathophysiological mechanisms. Systems biology allows the molecular information contained in urine to be used to understand the overall organization of the regulatory networks in the diseased kidney tissue. In my thesis we have applied systems biology with two aims : The first aim was to improve the understanding of the pathophysiological mechanisms of kidney disease based on the analysis of urine molecular composition. Since the information in urinary proteome is mainly limited to excreted proteins, it is essential to have bioinformatic analysis methods available to "trace back" the key proteins present in the kidney tissue, but not excreted in the urine. Since this type of method is not widely used in nephrology, I have developed a methodological tool to identify in silico new key actors in kidney disease from the analysis of the urinary proteome. This new tool, called PRYNT (PRioritization bY causal NeTworks), is based on the use of protein-protein interactions with a prioritization method to identify proteins in the network that preferentially interact with urinary protein biomarkers. The second aim of my thesis was to develop systems biology approaches for the detection and progression of kidney disease using the molecular composition of urine. We developed a quantitative approach to propose an answer to these questions. I then applied this approach to the analysis of the urinary metabolome and amniotic fluid peptidome. Modelling and statistical methods allowed in these contexts to predict the presence of kidney disease and its progression
Nabaa, Michel. "Morphodynamique de réseaux viaires - Application au risque". Phd thesis, Université du Havre, 2011. http://tel.archives-ouvertes.fr/tel-00623691.
Texto completo da fonteCharbaut, Elodie. "Parenté et diversité fonctionnelles des protéines de la famille de la stathmine". Paris 6, 2003. http://www.theses.fr/2003PA066049.
Texto completo da fonteAchoch, Mounia. "Méthodes d’apprentissage et approches expérimentales appliqués aux réseaux d’interfaces protéiques". Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAA022/document.
Texto completo da fonteThe aim of this study is to understand protein assembly mechanisms. The assembly of a protein in an oligomer is particularly important because it is involved in many pathologies going from bacterial infection, Alzheimer like diseases or even some cancers. Protein assembly is the combination of two or more protein chains to induce a biological activity. The B subunit of the cholera toxin pentamer (CtxB5), which belongs to the family of AB5 toxins, is studied as the main model of assembly. Experimental results have provided information on the assembly of the toxin highlighting the involvement of certain amino acids. The first problem addressed in my thesis is to understand their role and see if network approaches are relevant to such investigation. I was able to show using amino acid mutations, that amino acids influence each other by cascade or "peer to peer" mechanisms in order to coordinate the various steps of the assembly (Chapters 4, 5 and 6). The structure and function of the proteins are defined by amino acid sequences which naturally vary due to genetic mutation. So I decided to expand this field of investigation to see if the cascade mechanism was generalized as a mean of disrupting a protein structure. Here it is to understand how a protein loses its function by way of a significant change of structure upon mutation. First, I studied dataset to know the characteristics of healthy protein networks (Chapter 7, 8 and 9), and after I looked at the effects of the systematic mutation of each amino acid of CtxB5 on its overall structure (Chapter 10 and 11). Mutations led from moderate to very large structural changes around the mutated amino acid or at long distances. These results are consistent with known effects of mutation: robustness (maintenance function), evolution or adaptation (emergence of a new feature) and fragility (pathologies). The results also show a weak correlation between the number of amino acid contacts of the mutated amino acid and the amount of structural change induced by its mutation. It is therefore not easy to anticipate the effect of a mutation: The last chapter of my thesis addresses this problem (Chapter 12)
Guillaume, Jean-Loup. "Analyse statistique et modélisation des grands réseaux d'interactions". Phd thesis, Université Paris-Diderot - Paris VII, 2004. http://tel.archives-ouvertes.fr/tel-00011377.
Texto completo da fonteLa première partie est centrée sur l'analyse des réseaux et fait un point critique sur les réseaux étudiés et les paramètres introduits pour mieux comprendre leur structure. Un certain nombre de ces paramètres sont partagés par la majorité des réseaux étudiés et justifient l'étude de ceux-ci de manière globale.
La seconde partie qui constitue le coeur de cette thèse s'attache à la modélisation des grands réseaux d'interactions, c'est-à-dire la construction de graphes artificiels semblables à ceux rencontrés en pratique. Ceci passe tout d'abord par la présentation des modèles existants puis par l'introduction d'un modèle basé sur certaines propriétés non triviales qui est suffisamment simple pour que l'on puisse l'étudier formellement ses propriétés et malgré tout réaliste.
Enfin, la troisième partie est purement méthodologique. Elle permet de présenter la mise en pratique des parties précédentes et l'apport qui en découle en se basant sur trois cas particuliers : une étude des échanges dans un réseau pair-à-pair, une étude de la robustesse des réseaux aux pannes et aux attaques et enfin un ensemble de simulations visant à estimer la qualité des cartes de l'Internet actuellement utilisées.
Cette thèse met en lumière la nécessité de poursuivre les travaux sur les grands réseaux d'interactions et pointe plusieurs pistes prometteuses, notamment sur l'étude plus fine des réseaux, que ce soit de manière pondérée ou dynamique. Mais aussi sur la nécessité d'étudier de nombreux problèmes liés à la métrologie des réseaux pour réussir à capturer leur structure de manière plus précise.