Дисертації з теми "Homéostasie – génétique"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-33 дисертацій для дослідження на тему "Homéostasie – génétique".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Ruchat, Stéphanie-May. "Étude des déterminants génétiques et des interactions gène-gène et gène-environnement associés à l'homéostasie glucidique." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26878/26878.pdf.
Повний текст джерелаWang, Ying. "Genetic dissection of adaptor molecules in lymphocyte development, homeostasis and function." Aix-Marseille 2, 2006. http://www.theses.fr/2006AIX22035.
Повний текст джерелаL’adaptateur transmembranaire LAT (Linker for Activation of T cells) constitue une plateforme moléculaire assurant le recrutement de nombreuses protéines impliquées dans la transduction des signaux médiés par le TCR. Les souris homozygotes pour une mutation ponctuelle de la tyrosine 136 du domaine intracytoplasmique de LAT présentent un défaut dans le développement des lymphocytes T. En outre, elles développent progressivement une lymphoprolifération T CD4+ polyclonale qui est associée à une éosinophilie tissulaire et à une maturation massive des cellules B en plasmocytes sécrétant des niveaux élevés d’IgG1 et d’IgE. Pour disséquer les mécanismes cellulaires et moléculaires associés au développement de cette pathologie, nous avons mis en oeuvre un système de transfert adoptif à court terme et à long terme dans des hôtes présentant une immunodéficience sélective en lymphocytes T. Nous avons montré que les cellules T CD4+ des souris mutantes LATY136F présentent une homéostasie similaire à celle des cellules wt en début de reconstitution. En revanche, 8 semaines après reconstitution, les cellules T CD4+ desLATY136F induisent une pathologie lymphoproliférative qui reproduit en tout point celle observée initialement dans les souris LATY136F. Ainsi, les souris reconstituées présentent-elles une accumulation massive de cellules T CD4+ et de lymphocytes B dans les organes lymphoïdes secondaires, une ypergammaglobulinémie IgG1 et IgE et une éosinophilie marquée dans de nombreux tissus. Ceci démontre que les lymphocytes T sont nécessaires et suffisants pour induire la pathologie LATY136F. Par comparaison des reconstitutions réalisées dans des hôtes déficients en CD3 et exprimant ou non les molécules d’histocompatibilité de classe II, nous avons établi que les lymphocytes T CD4+ LATY136F conservent, en l’absence de molécules d’histocompatibilité de classe II, leur capacité à proliférer et à stimuler la maturation des lymphocytes B en plasmocytes sécrétant des IgG1 et des IgE -avec une efficacité néanmoins deux fois moindre-. Ces résultats suggèrent que la lymphoprolifération des cellules T CD4+ dans les souris mutantes LATY136F et que la coopération T/B associée qui conduit à des concentrations sériques considérables d’IgE et IgG1 sont, pour une large part, indépendants des moléculesd’histocompatibilité de classe II. Ce comportement largement indépendant du TCR et pouvant à ce titre être qualifié de comportement autistique vis-à-vis des molécules de classe II apparaît comme une propriété unique des cellules T CD4+ portant la mutation LATY136F. NTAL (Non T cell Activation Linker, également appelé LAB) est un adaptateur transmembranaire récemment identifié qui possède des similarités structurales avec LAT. NTAL est fortement exprimé dans les cellules B, les cellules NK et les mastocytes. NTAL est rapidement phosphorylé par les kinases de la famille Src (Lck ou Fyn) et de la famille Syk (Zap-70 ou Syk) après engagement du récepteur des cellules B (BCR) ou des récepteurs au fragment Fc des immunoglobulines de type FcγRI et FcεRI. Les principales protéines identifiées comme associées à la molécule NTAL phosphorylée sont Grb2, SOS1, C-Cbl, Gab1. La suppression de l’expression de NTAL dans une lignée B conduit à une diminution des flux calciques et de l’activation des molécules Erk, ce qui suggère que NTAL participe à l’induction des flux calciques et à l’activation de la voie Ras-MAPKassociées à la stimulation du BCR. Pour identifier les rôles respectifs de NTAL et de LAT dans le développement et la fonction des lymphocytes B, des souris déficientes pour Ntal ont été générées et croisées avec des souris déficientes pour LAT. L’ analyse de ces souris a montré que les cellules B se développent avec la même efficacité dans les souris doublement déficientes Lat-/-Ntal-/-, dans les souris déficientes dans l’un de ces deux gènes et dans les souris wild-type, ce qui démontre que NTAL n’est pas indispensable pour le développement des lymphocytes B. L’agrégation des récepteurs des cellules B induit, par ailleurs, des niveaux de prolifération et des niveaux de flux calciques légèrement augmentés dans les souris déficientes pour Ntal. L’analyse des réponses humorales T dépendantes et T indépendantes a montré que les souris déficientes pour Ntal possèdent, en outre, des niveaux augmentés d’anticorps naturels et des réponses humorales légèrement amplifiées en réponse à des antigènes T dépendants. Des titres normaux d’immunoglobulines sériques spécifiques sont observés en réponse à des antigènes T indépendants. Enfin, bien que NTAL soit également exprimé dans les plasmocytes, son absence n’affecte pas l’hypergammaglobulinémie E et G1 sedéveloppant dans les souris porteuses de la mutation LATY136F. NTAL ne constitue donc pas dans les lymphocytes B l’équivalent fonctionnel de LAT dans les lymphocytes T
Mingueneau, Michaël. "Dissection génétique du récepteur pour l'antigène des lymphocytes T : codage proximal et conversion du signal "ligand", de sa reconnaissance à l'assemblage des signalisomes." Aix-Marseille 2, 2008. http://theses.univ-amu.fr.lama.univ-amu.fr/2008AIX22067.pdf.
Повний текст джерелаThe mechanisms by which ligand recognition is encoded and converted into a cytoplasmic signal by the T cell receptor (TCR), in particular how signals are initiated and terminated and how this code is adjusted during T cell differenciation are central themes in T cell immunology and constitute the subject of this work. Two main models have been proposed to account for signal initiation following ligand recognition by the TCR. In one model of T cell activation, the half‐lives of TCR:pMHC complexes constitute the main parameter driving T cell activation. In an alternative model, conformational changes of the receptor have been proposed to rationalize the seminal events leading to biochemical cascades. In particular, in one of the most recently advocated conformational model of T cell activation, a proline‐rich motif (PRS) located in the cytoplasmic tail of CD3ε has been proposed to be inducibly exposed following activation and to recruit the cytosolic adaptor NCK. According to that model, this step would occur even prior to phosphorylation events and would constitute a critical step for T cell activation. To assess this model, we constructed a knock‐in mouse deprived of this sequence. The phenotype of this mouse invalidated the conformational model of T cell activation based on an inducible exposure of this motif. Unexpectedly this mouse also unraveled novel functions for the PRS sequence at the β selection checkpoint, but also during γδ selection events and turned out to be a crucial regulator of TCR levels expressed on DP thymocytes and also required for positive selection events. These four functions were linked to the constitutive interaction between CD3εPRS and NCK and to the recruitment of LCK by NCK. Although this last interaction has to be directly demonstrated, the compensation of the phenotype by a pre‐activated LCK kinase strongly suggests that the functions associated with CD3εPRS:NCK interaction are mediated through LCK. These observations led us to formulate a model in which a tri‐molecular complex composed of CD3εPRS:NCK:LCK constitutes an intracellular coreceptor recruiting LCK in situations where the TCR is not or not efficiently coupled with CD4 and CD8 coreceptors, i. E. During β selection, γδ selection, in pre‐selected CD4+CD8+ thymocytes and during positive selection (where thymocytes recognize low‐affinity ligands that do not recruit efficiently the coreceptors due to the short half‐life of these ligands). Lastly, the function associated with the CD3εPRS in CD4+CD8+ thymocytes was linked to the participation of this sequence to a degradation pathway mediated by SLAP and c‐CBL leading to CD3ζ ubiquitination and degradation. In order to analyze signals that participate to the termination of activatory signals, we used the LatY136F/Y136F mouse genetic model in which the LAT adaptor is deprived of the tyrosine 136 and which develops a CD4 lymphoproliferative disorder. To understand the mechanisms at play in this pathology, we developed a conditional model allowing the expression of the mutation in peripheral T cells. This approach demonstrated that this disorder is not mediated by an auto‐immune mechanism and that a similar pathology occurs in complete absence of LAT adaptor, suggesting that altered LAT signals do not participate to the unfolding of the disease. Interestingly, the absence of LAT molecules led to the exacerbation of some of the biochemical events, unraveling in a direct fashion the negative regulatory function of LAT for T cell homeostasis
Pang, Yuanyu. "Caractérisation des cellules régulatrices CD4+CD25+FOXP3+ dans des conditions homéostatiques et au cours du GVHD." Paris 7, 2014. http://www.theses.fr/2014PA077013.
Повний текст джерелаUnderstanding the heterogeneity of human CD4+FOXP3+ regulatory T cells (Treg) and their potential for lineage-reprogramming is of critical importance for moving Treg therapy into the clinics. Using multi-parameter single-cell analysis techniques we explored the heterogeneity and functional diversity of human Treg in healthy donors and in patients after allogeneic hematopoietic stem cell transplantation (alloHSCT). Human Treg displayed a level of complexity similar to conventional CD4+ effector T cells with respect to the expression of transcription factors, homing receptors and inflammatory cytokines. Single-cell profiling of the rare Treg producing IL-17A or IFN-y showed an overlap of gene expression signatures of Th17 or TH1 cells and of Treg. To assess if Treg homeostasis is affected by an inflammatory and lymphopenic environment, we characterized the Treg compartment in patients early after alloHSCT. This analysis suggested a marked depletion of Treg with a naive phenotype in patients developing acute graft-versus-host disease, compared to tolerant patients. However, single-cell profiling showed that CD4+FOXP3+ T cells maintain the Treg gene expression signature and Treg suppressive activity was preserved. Our study establishes that heterogeneity at the single-cell level, rather than lineage-reprogramming of CD4+FOXP3+ T cells, explains the remarkable complexity and functional diversity of human Treg
Thomas, Charles. "Impact du cholestérol sur le cycle entérohépatique des acides biliaires : conséquences pour l'homéostasie lipidique." Dijon, 2006. http://www.theses.fr/2006DIJOS016.
Повний текст джерелаHypercholesterolemia is a major risk factor of cardiovascular diseases. Understanding of mechanisms ensuring the maintenance of body cholesterol homeostasis is crucial, since it can allow the development of new hypocholesterolemiant therapies. Bile Acids (BA) are end-products of cholesterol metabolism. These molecules, produced in the liver, participate to fat digestion and absorption in the intestine. Moreover, BA represent the main pathway of body cholesterol removal. The results presented in this thesis show that genes encoding intestinal, hepatic and renal BA transporters are coordinately regulated. This mechanism ensures efficient BA elimination through faecal and urinary route, and thus contributes to explain the resistance of mice to diet-induced hypercholesterolemia. The transcription factors SREBP-2 and HNF-1, and the nuclear receptor PPAR, play a key role in this adaptative process since they allow cholesterol-dependent regulation of several key BA transporters, particularly ASBT in the ileum and the kidney, and L-FABP in the liver
Demény, Maté Agoston. "Analysis of TAF8, a subunit of TFIID and SMAT (smal TAF complex), reveals novel regulation of the assembly of TAF-containing complexes." Université Louis Pasteur (Strasbourg) (1971-2008), 2006. http://www.theses.fr/2006STR13096.
Повний текст джерелаRoy, Gauthier. "Étude d'un système d'acquisition du cuivre chez Bordetella pertussis : nouveau mécanisme de régulation post-transcriptionnelle et caractérisation fonctionnelle préliminaire." Electronic Thesis or Diss., Université de Lille (2022-....), 2022. http://www.theses.fr/2022ULILS058.
Повний текст джерелаSeveral transition metals are essential micronutrients for most living beings, including bacteria. In addition, they play important roles at the host-pathogen interface: the host tends to restrict bacterial access to iron, manganese and zinc, while intoxicating invading microorganisms with copper or zinc during phagocytosis. Bacteria have therefore acquired various homeostasis mechanisms in order to adapt to those conditions. Whereas iron, zinc or manganese import systems have been extensively characterized, very little is known for copper, for which studies have mostly focused on defense mechanisms. Besides, while several post-transcriptional regulation mechanisms are known for other metals, only transcriptional regulators have been identified in response to copper.Previous work performed in the laboratory on copper homeostasis in the human-restricted pathogen Bordetella pertussis, responsible for the whooping cough disease, has shown that this bacterium has shed most of its defense mechanisms against excess copper. On the other hand, we have identified a three-gene operon called bp2923-bfrG-bp2921, in which the last two genes are down-regulated by copper excess. bfrG is notably predicted to encode a TonB-dependent transporter, a protein family well-known for metal import across the outer membrane in Gram-negative bacteria, and bp2921 has a characterized homolog encoding a siderophore reductase, which hints at a system involved in copper acquisition. We have shown that the protein encoded by the first gene, a member of the DUF2946 protein family, represents a new type of upstream Open Reading Frame (uORF) involved in post-transcriptional regulation of the downstream genes. In the absence of copper, the entire operon is transcribed and translated. Perception of copper by the nascent bp2923-coded protein via its conserved CXXC motif triggers Rho-dependent transcription termination between the first and second genes by relieving translation arrest on a conserved C-terminal RAPP motif. Homologs of bp2923 are widespread in bacterial genomes, where they head operons predicted to participate in copper importation or utilization. We have thus identified a new mode of genetic regulation by a transition metal and identified a regulatory function for a member of an uncharacterized family of bacterial proteins that we have named CruR, for Copper responsive upstream Regulator. Additional work on this system has shed a light on the complexity of bacterial regulation, as our operon is regulated not only by copper, but is also overexpressed upon virulence modulation or in stationary growth phase.We have also initiated the characterization of the function of this operon. BfrG has been shown to specifically bind copper in vitro, and phenotypic analyses have shown a crucial role for the operon when B. pertussis is placed in low-oxygen conditions. Among the cuproproteins produced by B. pertussis are several cytochrome oxidases in the respiratory chain, which suggests that BfrG and Bp2921 could play a role in delivering copper for their assembly. Combined with results on the regulation, this suggests a possible role for copper and our operon in bacterial persistence in the respiratory tract during infection. Many aspects of this system remain to be further investigated
Duc, Céline. "Identification des génes impliqués dans la signalisation du statut en fer chez les végétaux." Montpellier SupAgro, 2009. http://www.theses.fr/2009NSAM0018.
Повний текст джерелаDevergnas, Séverine. "Etude et caractérisation de l'expression de nouveaux transporteurs de zinc de la famille ZnT chez les mammifères." Université Joseph Fourier (Grenoble), 2005. http://www.theses.fr/2005GRE10237.
Повний текст джерелаZinc is an essential trace element. It is involved in many cellular processes because it is a cofactor of enzymes, nuc1ear factors and hormones. Therefore, is a very important component of cell viability Zinc homeostasis results from a coordinated regulation of different proteins: ZIP (uptake), metallothioneins (intracellular storage/trafficking), and ZnT (excretion). Using genomic databanks, we have analyzed and identified two novel SLC30 genes: SLC30A8 and SLC30A10. Zinc homeostasis is maintained by the action of these proteins, and their transcription is partly dependent of extra cellular zinc concentration. Ln case of zinc deficiency, ZnT-5, -5c and -7 genes are over-expressed. These transporters that we have localized in the Golgi apparatus could provide essential zinc to neo-synthesised proteins for their functionality. Furthermore, we showed that ZnT-8 is a zinc transporter specifie of pancreas and expressed in beta cells. ZnT -8 facilitates the accumulation of zinc from the cytoplasm into insulin vesic1es, and its transcription regulation is dependent, like insulin, of extra cellular glucose concentration. Zinc is implicated in all metabolic and structural aspects of the different cellular compartments. Therefore the cellular control of Zinc requires to be understood and is essential tot fear the cellular working
Chaste, Pauline. "Exploration de deux processus associés à l'autisme : la synaptogénèse et la signalisation de la mélatonine." Paris 7, 2010. http://www.theses.fr/2010PA077126.
Повний текст джерелаThe search for rare mutations or chromosomal rearrangements, has recently allowed new hypotheses regarding the genetic mechanisms involved in autism. Previous studies in the laboratory have allowed to show mutations of neuroligins 3 and 4, which encode neuronal cell adhesion molecules. My thesis was in the continuity of this work, pursuing a strategy of search of rare mutations in candidate genes. I studied the one hand MAGI2 gene, which encodes a partner of neuroligins, in 96 subjects with autism. On the other hand, I studied genes of the melatonin pathway in patients with autism, and ADHD subjects, to clarify the mechanisms and specificity of alterations of this pathway. Also my work has included clinical reevaluation of patients who carried mutations of SHANK3. The study of MAGI2 and SHANK3 genes showed that mutations in neuroligins partners may have a role in the emergence of an "isolated" autistic syndrome. However, the gene MAGI2 does not seem particularly involved in autism, and may be associated with a more severe phenotype. The study of the melatonin pathway confïrms the likely preponderance of a deficit of melatonin synthesis as a mechanism for alteration of this pathway in autism and that alteration of this pathway is not specific to autism. Finally, the two processes explored in this thesis could play a role in a common process; the maintenance of synaptic homeostasis
Moretto, Fabien. "Mise en évidence d’une nouvelle voie impliquée dans l’homéostasie de la taille cellulaire chez S. cerevisiae." Thesis, Bordeaux 2, 2012. http://www.theses.fr/2012BOR22002/document.
Повний текст джерелаCell size homeostasis implies that specific mechanisms are devoted to coordinating growth and proliferation. It is well established that cell size is affected by nutrient availability and ploidy but the underlying mechanisms are not elucidated. A genome wide search for yeast mutants affected for cell volume homeostasis, conducted in the Tyers’lab, revealed that the inactivation of about 400 genes leads to a median cell volume diverging from the isogenic wild-type. The cell size control process is thus a very interesting situation where multiple loci contributing to a complex quantitative trait have been identified but their organisation into distinct pathways and their respective influence remain largely to be elucidated. To address this issue, we started from the observation that a sir2 mutant shows an increased cell size. Consistently, nicotinamide (NAM), a Sir2 inhibitor, mimics the sir2 size defect in a Sir2p-dependent manner. This allowed us to identify among ~200 small size mutants, 22 mutants that were clearly not affected by NAM treatment. Strikingly, 16 out of the 22 NAM unresponsive mutants affected biogenesis of the large ribosomal subunit (named 60S below). Consistently, diazaborine, a drug that blocks the large ribosomal subunit assembly and therefore mimics 60S mutants, rendered wild-type yeast cells smaller. A set of ~200 large mutants were treated with diazaborine and their cell volume was measured. This chemogenetics approach allowed us to identify 31 diazaborine-unresponsive mutants, including swi4 and swi6, two major cell cycle regulators that are critical for cell size control. These results were confirmed by constructing double mutants. This work shows that it is possible to organize cell size mutants in specific pathways and to define clear epistasis relationships between them. Our data indicate that the control of cell size by the “Sir2-60S” pathway is independent of both the ploidy and the nutritional control of cell size
Boudière, Laurence. "Analyse de l'homéostasie des lipides membranaires d'Arabidopsis thaliana par une stratégie de génétique chimique exploitant une nouvelle classe d'analogues du diacylglycérol." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-01062179.
Повний текст джерелаNouvian, Régis. "Rôle du canal potassique KCNQ4 dans la cochlée des mammifères : approches pharmacologique et génique." Montpellier 2, 2004. http://www.theses.fr/2004MON20231.
Повний текст джерелаFourgeux, Cynthia. "Cholestérol-24S-hydroxylase (CYP46A1) et homéostasie du cholestérol dans la rétine en conditions physiologiques et pathologiques." Phd thesis, Université de Bourgogne, 2012. http://tel.archives-ouvertes.fr/tel-00905888.
Повний текст джерелаZaghini, Isabelle. "Le gène de l'I-BABP : implication dans l'homéostasie du cholestérol ?" Dijon, 2001. http://www.theses.fr/2001DIJOS044.
Повний текст джерелаGaudreault, Manon. "Modulation de l'expression du gène encodant la sous-unité d'intégrine α6 durant la cicatrisation cornéenne". Doctoral thesis, Université Laval, 2007. http://hdl.handle.net/20.500.11794/19463.
Повний текст джерелаDiallo, Lisa. "Criblage génétique à la recherche de nouveaux gènes essentiels influençant l’homéostasie des télomères chez Saccharomyces cerevisiae : Un défi de tailles." Mémoire, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9531.
Повний текст джерелаAbstract : In the yeast Saccharomyces cerevisiae, the regulation of telomere length reflects the offset between erosion mechanisms (exonucleases, semi-conservative replication and resection), elongating factors (via the telomerase reverse transcriptase, which is found in 90 % of human cancers) and actions of various specific telomeric regulatory proteins, which collectively confer telomeres their property of being a "Cap" that protects the ends of eukaryotic chromosomes. To determine whether essential genes that can not be suppressed also play a role in telomere homeostasis, I realized a genetic screen with yeast tet-off mut ants in which a significant under-expression of an essential gene was induced. This allows to study the resulting effects on telomere homeostasis. Overall, my work dealt with more than 662 essential genes for which I analyzed the telomere length phenotypes qualitatively by comparing telomere lengths in mutant strains to those in wild-type strains. Furthermore, via technical improvements that I developed, a quantification of the sizes of telomeric repeats from 300 of these strains was determined. It is notable that all essential genes studied here have very different effects resulting in chromosomes with very unequal lengths of telomeres. For nearly 40% of the analyzed mutants, telomeres sizes appeared to be critically different from those in wt yeast. Many of these essential genes are involved in mechanisms affecting the cell cycle, DNA replication, DNA repair, etc. The majority of genes revealed in our screen provide important additional information to an almost non-existing literature on the effects of essential genes on yeast telomere biology. This is particularly the case for underexpressing the gene YHR122W (yielding long telomeres) and YOR262W (yielding short telomeres). Both genes hence emerged from my results as necessary to maintain telomere homeostasis and collectively they are part of a large set of genes I called ETL genes for Essential for Telomere Length.
Demarque, Maud. "Rôle de la voie SUMO dans le développement, l'homéostasie intestinale et la transformation tumorale chez la souris." Paris 7, 2009. http://www.theses.fr/2009PA077165.
Повний текст джерелаSUMO is a modifier peptide related to ubiquitin and involved in numerous cellular processes. To investigate the role of the SUMO modification (or sumoylation) in mammals, we chose to target Ubc9, the unique SUMO E2 conjugating enzyme for SUMO. To circumvent the embryonic lethality encountered with the constitutive inactivation of Ubc9,1 generated several mice lines displaying a partial or conditional inactivation of Ubc9. Our study reveals a crosstalk between sumoylation, cellular proliferation and mouse embryonic or adult growth. We also show that partial inactivation of sumoylation impairs the transformation capacities of cells in culture or in xenograft into Nude mice. The study of inducible knock-out mice for Ubc9 reveals an additional role for sumoylation in maintaining the intestinal homeostasis
Coleno-Costes, Anne. "Rôle de l'ETP Corto et de la protéine ribosomique RPL12 dans la régulation transcriptionnelle chez Drosophila melanogaster." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00828236.
Повний текст джерелаMastrogiannaki, Maria. "Rôle des facteurs de transcription HIF (Hypoxia Inducible Factors) hépatiques et intestinales dans la régulation de l'homéostasie du fer." Paris 5, 2011. http://www.theses.fr/2011PA05T008.
Повний текст джерелаHepcidin, a liver expressed hormone, is the central regulator of iron homeostasis and is decreased in response to hypoxia and iron deficiency. In contrast, intestinal iron absorption is upregulated during these conditions. Hypoxia Inducible Factors, HIF-1 and HIF-2, are ironand hypoxia-regulated transcription factors, and the central regulators of mammalian oxygen homeostasis. During my thesis, I generated intestinal-specific and liver-specific HIF knockout mouse models in order to investigate in physiopathological conditions the links between HIF signaling and i) the regulation of hepatic hepcidin expression, and ii) the regulation of intestinal iron absorption. I demonstrated that HIF-2 is dispensable for the regulation of hepcidin in conditions of iron deficiency or hypoxia. However, I showed that HIF-2, upon stabilized in physiopathological conditions, induces hepcidin repression, indirectly through increased Erythropoietin (EPO) production and the regulation of erythropoiesis. In the intestine, I showed that HIF-2, but not HIF-1, controls iron absorption by regulating the expression of DMT1 (Divalent Metal Transporter-1) and DCYTB (Duodenal cytochrome b) proteins which import iron in the enterocytes. Finally, I demonstrated that HIF-2 is involved in the regulation of iron hyper-absorption in a genetic mouse model of hereditary hemochromatosis (HH). HH is a genetic disorder characterized by abnormally low hepcidin expression and excessive iron accumulation in the liver and parenchyma. These findings suggest a prominent role of HIF-2 in the physiopathological regulation of intestinal iron absorption and may provide new therapeutical perspectives for the treatment of anemias and iron overload-associated disorders
Vannier, Jean-Baptiste. "Rôle de protéines de la réparation des cassures double brin dans l'homéostasie télomérique chez Arabidopsis thaliana." Phd thesis, Université Blaise Pascal - Clermont-Ferrand II, 2009. http://tel.archives-ouvertes.fr/tel-00725958.
Повний текст джерелаDaher, Marie Thérèse. "Rôle du facteur de transcription Bcl11b dans l’homéostasie et le remodelage cardiaque." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS064.
Повний текст джерелаBcl11b is a transcription factor that acts both as a transcriptional repressor and activator in a context dependent way. A genetic study in humans revealed the association between common genetic variations in the Bcl11b locus and increased risk for cardiovascular disease. Microarray data comparisons showed that Bcl11b could modulate the expression of genes during cardiac hypertrophy. This suggests that studying Bcl11b in the heart may be of major interest. For this, we generated cardiac-specific Bcl11b KO mice (Bcl11b-HKO) and analyzed them at several time points. We observed that the inactivation of Bcl11b in adult mice altered cardiomyocytes’ homeostasis 7 days after Bcl11b’s KO and induced cell death. This causes the activation of repair mechanisms and cardiac remodeling: inflammation, fibrosis, hypertrophy, followed by a decrease in contractile function two months after Bcl11b’s inactivation. Cell death is also observed in Bcl11b-KO primary cardiomyocytes cultures. On the other hand, we observed a disturbance of circadian rhythm gene expression, especially in the pre-sleep period in Bcl11b-HKO mice. In parallel, we characterized the binding of Bcl11b on the proximal promoter region of the βMHC, skActin and cActin genes in a hypertrophic context using ChIP-qPCR experiments. We believe that Bcl11b participates in the regulation of genes involved in cardiac hypertrophy. In conclusion, my thesis work highlights the importance of Bcl11b to cardiac homeostasis through the role it could play in the regulation of cardiac circadian rhythm and its possible role in the regulation of hypertrophic mechanisms
Advedissian, Tamara. "Identification d'une nouvelle fonction de galectine-7 comme modulateur de l'adhérence intercellulaire dans les cellules épithéliales." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC036/document.
Повний текст джерелаGalectins composed a family of soluble lectins implicated in multiple processes. They are characterized by the presence of a carbohydrate recognition domain evolutionary conserved and an affinity for β-galactosides containing sugars. During this thesis, we focused on a protein called galectine-7 whose expression is restricted to stratified epithelia such as the epidermis. Using mouse models with altered expression of galectin-7, our team previously showed that this protein participates in intercellular adhesion and collective cell migration, two key processes in tumour progression and epidermal wound healing. However, the underlying mechanisms remain to be elucidated. Combining different approaches, we discovered that the migration delay observed in the absence of galectin-7 during wound healing could be explained, at least in part, by a reduction of cell coordination and collective cell behaviour of migrating keratinocytes. Moreover, our data showed that galectin-7 directly interact with E-cadherin, a key component of adherent junctions and a major player in collective migration. Surprisingly, this binding did not involve carbohydrate groups. Aiming to precise the role of galectin-7 at adherent junctions, we identified a new function of galectin-7 in the stabilisation of E-cadherin at the plasma membrane. Interestingly, the increased of E-cadherin turnover caused by galectin-7 extinction is also associated to a decreased of the strength of adherent junctions-based intercellular adhesion. Eventually, our experiments indicated that this previously unknown function of galectin-7 required a functional lectin activity, suggesting the involvement of an additional glycosylated actor in this regulation mechanism of E-cadherin dynamics by galectin-7.In conclusion, this thesis allowed to precise the role of galectin-7 in collective cell migration and revealed a novel function of galectin-7 in the regulation of the E-cadherin stability at the plasma membrane. This modulatory effect of galectin-7 on E-cadherin could provide the cell a possible adaptive response to environmental perturbations, as during collective cell migration. Indeed, galectins, because they exhibit rapid redistribution capacities, are good candidates to create adaptive responses
Boyer, Karène. "Identification de nouveaux réseaux génétiques impliqués dans la régulation de l'homéostasie des cellules hématopoïétiques chez la drosophile." Toulouse 3, 2012. http://thesesups.ups-tlse.fr/1989/.
Повний текст джерелаIn metazoans, the hematopoietic system plays a key role both in normal development and in defense of the organism. In Drosophila, the cellular immune response involves three types of blood cells: plasmatocytes, crystal cells and lamellocytes. This last cell type is barely present in healthy larvae, but its production is strongly induced upon wasp parasitization or in mutant contexts affecting larval blood cell homeostasis. Notably, several zygotic mutations leading to melanotic mass (or "tumor") formation in larvae have been associated to the deregulated differentiation of lamellocytes. To gain further insights into the gene regulatory network and the mechanisms controlling larval blood cell homeostasis, we conducted a tissue-specific loss of function screen using hemocyte-specific Gal4 drivers and UASdsRNA transgenic lines. By targeting around 10% of the Drosophila genes, this in vivo RNA interference screen allowed us to recover 59 melanotic tumor suppressor genes. In line with previous studies, we show that melanotic tumor formation is associated with the precocious differentiation of stem-cell like blood progenitors in the larval hematopoietic organ (the lymph gland) and the spurious differentiation of lamellocytes. We also find that melanotic tumor formation can be elicited by defects either in the fat body, the embryo-derived hemocytes or the lymph gland. In addition, we provide a definitive confirmation that lymph gland is not the only source of lamellocytes as embryo-derived plasmatocytes can differentiate into lamellocytes either upon wasp infection or upon loss of function of the Friend of GATA cofactor Ushaped. In this study, we identify 55 genes whose function had not been linked to blood cell development or function before in Drosophila. Moreover our analyses reveal an unanticipated plasticity of embryo-derived plasmatocytes, thereby shedding new light on blood cell lineage relationship, and pinpoint the Friend of GATA transcription cofactor U-shaped as a key regulator of the plasmatocyte to lamellocyte transformation
Villette, Claire. "Isoprenoid biosynthesis, specificities and homeostasis in plants : genetic approach for the identification of regulators by screening for suppressors of growth defect." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ017/document.
Повний текст джерелаPlants produce a great diversity of natural compounds, among which isoprenoids prevail. These molecules have essential functions for growth and development: plant hormones, growth regulators as brassinosteroids, photosynthetic pigments, acting on major biological processes. Thus, germination, flowering, heat and draught stress tolerance, or seed production are controlled by the action of isoprenoids. The aim of my project is to identify by genetic selection the regulators of isoprenoid homeostasis. For this, I carried out genetic screens for suppressors of growth defects in two isoprenoid biosynthesis deficient Arabidopsis thaliana mutants and a brassinosteroid signaling Hordeum vulgare mutant. The second part of my project was focused on the specific sterol biosynthetic pathway occurring in a specialized cell type, the germinating pollen tube
Chèvre, Jean-Claude. "Etude des déterminants génétiques du diabète de type MODY." Paris 6, 2000. http://www.theses.fr/2000PA066594.
Повний текст джерелаCelton, Magalie. "Etude de la réponse de Saccharomyces cerevisiae à une perturbation NADPH par une approche de biologie des systèmes." Thesis, Montpellier, SupAgro, 2011. http://www.theses.fr/2011NSAM0023/document.
Повний текст джерелаThe elucidation of the properties of metabolic network is essential to increase our understanding of cellular function and to design metabolic engineering strategies. The objective of this thesis was to better understand the regulation of the metabolism of NADPH, a “hub” metabolite which plays a central role in many cellular processes in Saccharomyces cerevisiae during fermentation. We used a systematic approach combining modeling and multi-“omics” analyses to study quantitatively the response to a perturbation of the NADPH demand. An original experimental system, based on the expression of a modified NADPH-dependent butanediol dehydrogenase was used to increase the demand for NADPH in a controlled manner. Through the use of this device and the development and use of a stoichiometric model of yeast dedicated to the fermentation, we predicted the flux distribution for different levels of perturbation. These experiments showed, first, the overwhelming ability of yeast to cope with very high NADPH demand, up to 40 times the anabolic demand. For a moderate level (up to 20 times the anabolic demand), the perturbation is mainly compensated by increased flux through the pentose phosphate pathway (PPP) and to a lesser extent through the acetate pathway (Ald6p). For a high NADPH demand, corresponding to 40 times the anabolic demand, the model predicts the saturation of the PPP as well as the operation of the glycerol-DHA cycle, which allows the exchange of NADH to NADPH. Fluxomics (13C), metabolomics and transcriptomics data were used to validate and to complement these hypotheses. We showed different levels of control depending on the intensity of the perturbation: for moderate demands, flux remodeling is mainly achieved by enzymatic control; for a high demand, a transcriptional control is observed for several genes of the PPP as well as some genes of the amino acids biosynthetic pathways, this latter effect being likely due to the low NADPH availability. Overall, this work has shed new light on the mechanisms governing NADPH homeostasis and more generally the intracellular redox balance
Briens, Mickaël. "Rôle de la sélénoprotéine N dans les réseaux de régulation rédox : études physiologique et transcriptomique." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ038/document.
Повний текст джерелаOxidative stress response plays a major function in the adaptation of biological systems. Selenoproteins have a main role in oxidative stress control. Mutations in the gene coding for the selenoprotein N (SelN) cause different muscular dystrophies in Humans but the molecular function of SelN is still unknown. The main objective of my PhD was to determine the molecular function of SelN, and its role in Redox regulation mechanisms. The Sepn1-/- mouse model was a central tool to reach those objectives.The key results revealed a higher sensibility of Sepn1-/- mice to specific oxidative or reticular stress inducers. Moreover, the Sepn1-/- mouse model was characterized by high throughput sequencing, comparing gene expression of paravertebral muscle of Sepn1-/- and wild type animals. Results showed activation of 580 genes in Sepn1-/- mice despite the absence of muscular phenotype in those conditions. Activated genes are coding for secreted proteins and indicated the activation of several metabolic pathways. Those results participated to Sel N function determination in the endoplasmic reticulum
Soualhi, Salima. "Rôles de SOX9 dans l’auto-renouvellement et la différenciation de l’épithélium intestinal." Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON13519.
Повний текст джерелаSox9 is a transcription factor expressed during the intestinal development and its expression is maintained throughout adult age in at least three populations of cells: stem cells, Paneth cells and tuft cells. Sox9 inactivation in the embryonic intestinal epithelium leads to crypts hyperplasia and to the loss of the Paneth cell lineage. The aim of this project is to determine Sox9 function in the adult intestinal epithelium, especially its role in Paneth cells (which function is altered in patients affected by inflammatory diseases such as Crohn disease), to identify how Sox9 controls proliferation and to propose molecular targets of Sox9 in tuft cells. Using mice models to inactivate Sox9 in adult intestinal epithelium, we could show that Sox9 is required to limit proliferation in the crypts, thus validating the hypothesis that Sox9 regulates negatively proliferation. Our results indicate that Sox9 is essential to maintain Paneth cells identity and we proposed that it ensures this function by repressing genes specific for Goblet cells differentiation: Muc2 and Klf4. Loss of Sox9 in Paneth cells is associated with a reduction of antimicrobial molecules which causes intestinal dysbiosis. In a specific environment (in presence of the « mouse norovirus »), Sox9-deficient mice have a defective intestinal permeability and are more susceptible to inflammation. The dysfunctions of the mucosal defences and of immunity responses in our model resemble those observed in Crohn patients, thus suggesting a potential implication of Sox9 in this pathology. In addition, these alterations could be responsible for the increased susceptibility of our deficient model to develop tumors in the context of a mutation of the tumor suppressor gene Apc. We started to unravel potential molecular targets of Sox9 that are involved in the control of proliferation, that will be important to better understand Sox9 function in the intestinal epithelium self-renewal and to identify precisely Sox9 function to maintain homeostasis and during intestinal tumorigenesis
Consentino, Laurent. "Mécanismes d'acquisition du fer de l'hôte chez Bacillus cereus : rôle du couple bacillibactine-FeuA et expression des gènes impliqués dans l'homéostasie du fer in vivo durant l’infection intestinale chez l’insecte." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLA018/document.
Повний текст джерелаIron acquisition is essential for most living organisms, including many pathogenic bacteria. However, free iron is toxic: it is bound into storage or transport proteins (e.g. ferritin, hemoproteins…) and iron homeostasis is tightly regulated. To scavenge iron from these sources, bacteria possess several systems to acquire the bound iron, by surface proteins or siderophores. Bacillus cereus is a sporeforming Gram-positive bacterium, opportunistic human pathogen, 2nd cause of food-borne disease in France. It has been demonstrated that the B. cereus surface protein IlsA and the siderophore bacillibactin (BB) are involved in iron acquisition from ferritin and that these two molecules are important for infection of the insect model G. mellonella. My thesis project focused on two parts: first the study of the BB-Fe3+ complex import into the cell by the siderophore binding protein FeuA highlights the central role of both BB and FeuA. The deletion of the genes encoding for these two molecules limits iron acquisition by B. cereus from ferritin, heme, hemoglobin and inorganic iron in vitro. On the other hand, the virulence phenotype during intra-haemocelic infection of G. mellonella is similar to the Wild-type strain. These results suggest a possible feedback on the expression of virulence factor genes when B. cereus is unable to synthetize both BB and FeuA, and therefore are under high stress. The second part of my work focused on the expression of genes involved in iron homeostasis in vivo, during gut infection of germ-free larvae of G. mellonella. We chose to perform a microgenomic approach, using laser-capture microdissection to get small samples in targeted areas, and then analysing the expression of chosen genes by RT-qPCR and ddPCR at two time points post ingestion The results show that : i) the colonisation of G. mellonella gut is impacted when B. cereus is deprived of both BB and FeuA ; ii) ilsA is expressed during gut infection ; iii) iron homeostasis is involved in adaptation and pathogenicity from the early step of infection of the insect gut ; iv) only weak gene expression modulation occured between the two timepoints This work gives new fundamental knowledge about B. cereus iron homeostasis, and highlights the use of new techniques regarding the in situ study of host-pathogen interactions
Marchal, Alexandre. "Larch hybrid vigor and role of the phenotypic plasticity in the construction of heterosis." Thesis, Orléans, 2018. http://www.theses.fr/2018ORLE2014/document.
Повний текст джерелаEuropean larch (Larix decidua) has been historically exploited within its natural rangefor its high quality wood, but the attempt to grow this species outside its native range was a failure. Hybridization with Japanese larch (L. kaempferi) is a promising path, in particular because of the heterosis this hybrid manifests. In this dissertation, we took advantage ofan old-enough, multi-site experiment with an inter-/intra-specific mating design. The first chapter presents the analysis of several traits involved in wood quality and productivity. We confirmed heterosis for volume related traits. The heterosis came with no counter part inwood quality, and it was stable across sites. Contrarily, some other traits showed no heterosis but higher heritabilities, and the additive performances for these traits were stable across sites and in pure species vs. in hybridization. In the second chapter, we investigated the role of phenotypic plasticity of some wood formation traits in the construction of the heterosis. Hybrid larch appeared as the most plastic taxon: it equaled the parental controls in producing narrow growth increments under drought, but it produced the largest rings in favorable water availability conditions. This second chapter was also a first step towards a better understanding of the role of phenotypic plasticity on the construction of the genetic variance architecture between larch stem circumference and density. The dissertation ends with a synthesis in which we discussed the implicationof our findings for the breeding of hybrid larch
Riah, Victor Omar. "Contribution à l'étude des addictions: La Cotinine, du tabagisme aux gènes." Habilitation à diriger des recherches, 2003. http://tel.archives-ouvertes.fr/tel-00472018.
Повний текст джерелаdo, Couto Bordignon Pedro. "An analysis of translation heterogeneity in ribosome profiling data." Thesis, 2019. http://hdl.handle.net/1866/24470.
Повний текст джерелаProteins are responsible for virtually all functions performed within and in the surroundings of a cell. The control of gene expression, which determines the amount, localisation and timing of protein production in the cell, is the central processes in the regulation of cellular physiology and function. Any disturbance in this complex system can generate important consequences on cellular integrity, sometimes leading to incurable diseases. The translation of messenger RNA into a protein product is the last step of the gene expression mechanism. It can be regulated in manifold ways, both intrinsically and extrinsically to the transcript sequence. It is also the costliest cellular process in terms of energy. Ribosome profiling (Ribo-Seq) is one of the recent and promising technologies making it possible to better study the mechanisms of translation regulation. Its results have however been shown to display variability in reproducibility and to contain noise of uncharted sources. This work presents the implementation of a strategy for dissociating signals of biological origin from those of technical origin. This is performed by the computation of a consensus profile of ribosomal density derived from a comparative analysis of several Ribo-Seq experiments in yeast (Saccharomyces cerevisiae). The biological signals derived by the consensus profiles correspond with signatures of known ribosomal pauses, such as mRNA folding strength and amino acid charges. Amazingly, our strategy also enabled the identification of differentially transcribed (DT) sequences. The latter have shown an over-representation of codons associated with modifications of transfer RNAs (tRNAs). They are also involved in the control of cellular homeostasis, exhibiting a marked presence in genes involved in ribosome biosynthesis as well as in mRNAs with precise translation sub-localization, particularly in mitochondria and the endoplasmic reticulum (ER). In addition to demonstrating the possibilities of discovery offered by the Ribo-Seq technique, this study also presents evidence of the dynamic and heterogeneous nature of the translation process in the eukaryotic cell. It also showcases its diverse regulatory mechanisms and the role of information directly encoded in the sequence in the general optimization of cellular homeostasis.