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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Compartimentalisation muqueuse de l’infection par le Virus de l'Immunodéficience Humaine (VIH) et impact de la réponse immunitaire / Mucosal compartmentalization of the Human Immunodeficiency Virus (HIV) infection and impact of the cellular immune response

Rubbo, Pierre-Alain 15 December 2011 (has links)
Bien que des progrès aient été réalisés dans la lutte contre la transmission du VIH depuis sa découverte il y a bientôt 30 ans, aucun outil thérapeutique actuellement sur le marché ne permet d'éliminer totalement le virus en 2011. Une meilleure connaissance des mécanismes physiopathologiques au niveau des compartiments muqueux, qui sont les principales portes d'entrée de l'infection par le VIH et abritent la majorité des lymphocytes T de l'hôte, est donc indispensable pour espérer éradiquer la pandémie. L'objectif de notre travail a été de caractériser les relations hôte-HIV dans le compartiment pulmonaire et génital ainsi que de décrire la synergie immuno-virologique entre le VIH et le virus herpès simplex (VHS) favorisant la transmission virale.Nous avons observé que les lymphocytes T sont présents en plus faibles proportions dans les sécrétions pulmonaires et génitales que dans le sang et ces cellules ont plus fréquemment un phénotype mémoire et activé. Les lymphocytes T muqueux sont donc plus prompts à sécréter des virus que ceux du sang. L'infection par le VIH est également associée à une dérégulation de la réponse immune muqueuse de l'hôte pouvant favoriser sa réplication. De plus, la modification de l'environnement immunologique liée à la synergie entre le VIH et le VHS apparaît comme un phénomène qui pourrait avoir un impact dans la transmission de chacun des deux virus. Une vision intégrée de la réponse immunitaire muqueuse contre le VIH permettra d'identifier les mécanismes à l'origine de l'infection et de la transmission en tenant compte des spécificités du virus et de l'environnement local ainsi que des interrelations avec le compartiment circulant. Les futurs essais cliniques devront en outre tenir compte des caractéristiques des muqueuses et de l'infection par le VIH afin de développer des thérapies anti-infectieuses avec une efficacité optimale, y compris dans les pays du Sud où les populations sont les principales victimes du VIH. / Although scientific advances have occurred in the fight against HIV transmission since its discovery almost 30 years ago, no current therapeutic tool enables the complete elimination of this virus in 2011. A better understanding of the physiopathological mechanisms at the mucosal compartment levels, which are the main gateways of HIV infection and host the majority of body T lymphocytes, is therefore crucial to bring hopes for eradicating HIV pandemic. The aim of our work is to characterize the host-HIV relationships in the pulmonary and genital compartments as well as the immuno-virological synergy between HIV and the herpes simplex virus (HSV) favouring the viral transmission.We have observed small proportions of T lymphocytes were found in the pulmonary and genital secretions in comparison with blood; and these cells have a more frequent memory and activated phenotype. The mucosal T lymphocytes are therefore quicker to produce viral particles than the blood counterpart. HIV infection is also associated with a deregulation of the host mucosal immune response, which could favour its own replication. Moreover, change in the immunological environment related to the HIV/HSV synergy appears as a phenomenon that could have an impact on each of the two viruses transmission.An integrated view of the mucosal immune response against HIV will allow identifying the mechanisms leading to the infection and transmission, taking into account the viral and local environment specificities as well as the interrelations within the circulating compartment. In addition, future clinical trials will have to take into account the HIV infection, the mucosal characteristics in order to develop anti-infectious therapy with an optimal efficiency, and the developing countries where the populations are the main victims of HIV.
2

Estudo geoambiental da bacia do Rio Pardo, a partir da compartimentação em Ottobacias - Escala 1:100.000 / Geoenvironmental study of Pardo River basin from Ottobacias compartimentalization - scale 1:100.000

Fontes, Silvana Brandão 04 October 2004 (has links)
Este trabalho apresenta um método de análise e compartimentação do meio físico que combina a subdivisão em Ottobacias (Pfafstetter, 1987) com cartografia geotécnica. Inicialmente a bacia foi dividida em 9 áreas, representadas pelas 4 maiores sub-bacias do rio Pardo e as 5 áreas restantes, denominadas interbacias. Em seguida, as informações dos atributos, substrato rochoso, materiais inconsolidados, declividade, drenagem e landforms, obtidos por técnicas de cartografia geotécnica, foram analisados em cada uma dessas unidades. Aquelas que não apresentaram predomínio de pelo menos 70%, quanto aos atributos analisados, foram subdivididas até atingirem este nível de homogeneidade. Na última etapa, as Ottobacias obtidas foram reagrupadas de maneira a se obter as unidades de compartimentação, respeitando semelhanças entre elas de pelo menos 70% dos atributos analisados. Esta compartimentação conduziu a obtenção de 90 unidades, pertencentes a 15 subgrupos que tiveram suas aptidões e restrições geoambientais analisadas. Este procedimento de compartimentação e análise mostrou-se adequado ao estudo em escala regional, principalmente em bacias de grandes dimensões, como é o caso da bacia do rio Pardo, fornecendo as bases para um estudo geoambiental mais detalhado. / This work presents a method of analysis and compartimentalization of the environment that combines the subdivision in Ottobacias (Pfafstetter, 1987) with engineering geological mapping. Initially the basin was divided in 9 areas, represented by the 4 larger Pardo river sub-basins and the remaining 5 areas called interbasins. Furthermore, the characteristics of the attributes, rocky substratum, unconsolidated materials, slope, drains and landforms were obtained by engineering geological mapping and then analyzed in each one of these units. The areas that have not predominance of at least 70%, for the analyzed attributes, were subdivided until reaching this level of homogeneity. In the last stage, the obtained Ottobacias were regrouped in order to have compartiments with similarities at least 70%, considering the analyzed attributes. This compartimentalization leads to the attainment of 90 units. These units belong to 15 sub-groups which their aptitudes and geoenvironmental restrictions were further analyzed. This compartimentalization procedure and analysis were shown to be adequate for regional scales investigation, mainly in basins of great dimensions, as it is the case for the Pardo river basin. This compartimentalization and analyses provide bases for more detailed geoenvironmental studies.
3

Estudo geoambiental da bacia do Rio Pardo, a partir da compartimentação em Ottobacias - Escala 1:100.000 / Geoenvironmental study of Pardo River basin from Ottobacias compartimentalization - scale 1:100.000

Silvana Brandão Fontes 04 October 2004 (has links)
Este trabalho apresenta um método de análise e compartimentação do meio físico que combina a subdivisão em Ottobacias (Pfafstetter, 1987) com cartografia geotécnica. Inicialmente a bacia foi dividida em 9 áreas, representadas pelas 4 maiores sub-bacias do rio Pardo e as 5 áreas restantes, denominadas interbacias. Em seguida, as informações dos atributos, substrato rochoso, materiais inconsolidados, declividade, drenagem e landforms, obtidos por técnicas de cartografia geotécnica, foram analisados em cada uma dessas unidades. Aquelas que não apresentaram predomínio de pelo menos 70%, quanto aos atributos analisados, foram subdivididas até atingirem este nível de homogeneidade. Na última etapa, as Ottobacias obtidas foram reagrupadas de maneira a se obter as unidades de compartimentação, respeitando semelhanças entre elas de pelo menos 70% dos atributos analisados. Esta compartimentação conduziu a obtenção de 90 unidades, pertencentes a 15 subgrupos que tiveram suas aptidões e restrições geoambientais analisadas. Este procedimento de compartimentação e análise mostrou-se adequado ao estudo em escala regional, principalmente em bacias de grandes dimensões, como é o caso da bacia do rio Pardo, fornecendo as bases para um estudo geoambiental mais detalhado. / This work presents a method of analysis and compartimentalization of the environment that combines the subdivision in Ottobacias (Pfafstetter, 1987) with engineering geological mapping. Initially the basin was divided in 9 areas, represented by the 4 larger Pardo river sub-basins and the remaining 5 areas called interbasins. Furthermore, the characteristics of the attributes, rocky substratum, unconsolidated materials, slope, drains and landforms were obtained by engineering geological mapping and then analyzed in each one of these units. The areas that have not predominance of at least 70%, for the analyzed attributes, were subdivided until reaching this level of homogeneity. In the last stage, the obtained Ottobacias were regrouped in order to have compartiments with similarities at least 70%, considering the analyzed attributes. This compartimentalization leads to the attainment of 90 units. These units belong to 15 sub-groups which their aptitudes and geoenvironmental restrictions were further analyzed. This compartimentalization procedure and analysis were shown to be adequate for regional scales investigation, mainly in basins of great dimensions, as it is the case for the Pardo river basin. This compartimentalization and analyses provide bases for more detailed geoenvironmental studies.
4

Arcabou?o geof?sico, isostasia e causas do magmatismo cenoz?ico da prov?ncia Borborema e de sua margem continental (Nordeste do Brasil)

Oliveira, Roberto Gusm?o de 27 July 2008 (has links)
Made available in DSpace on 2015-02-24T19:48:36Z (GMT). No. of bitstreams: 1 RobertoGO_Capa_ate_pag82.pdf: 4449318 bytes, checksum: a8a67621781bd4f76c4e2c0361bcc6a2 (MD5) Previous issue date: 2008-07-27 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The Borborema Province (BP) is a geologic domain located in Northeastern Brazil. The BP is limited at the south by the S?o Francisco craton, at the west by the Parna?ba basin, and both at the north and east by coastal sedimentary basins. Nonetheless the BP surface geology is well known, several key aspects of its evolution are still open, notably: i)its tectonic compartmentalization established after the Brasiliano orogenesis, ii) the architecture of its cretaceous continental margin, iii) the elastic properties of its lithosphere, and iv) the causes of magmatism and uplifting which occurred in the Cenozoic. In this thesis, a regional coverage of geophysical data (elevation, gravity, magnetic, geoid height, and surface wave global tomography) were integrated with surface geologic information aiming to attain a better understanding of the above questions. In the Riacho do Pontal belt and in the western sector of the Sergipano belt, the neoproterozoic suture of the collision of the Sul domain of the BP with the Sanfranciscana plate (SFP) is correlated with an expressive dipolar gravity anomaly. The positive lobule of this anomaly is due to the BP lower continental crust uplifting whilst the negative lobule is due to the supracrustal nappes overthrusting the SFP. In the eastern sector of the Sergipano belt, this dipolar gravity anomaly does not exist. However the suture still can be identified at the southern sector of the Maranc? complex arc, alongside of the Porto da Folha shear zone, where the SFP N-S geophysical alignments are truncated. The boundary associated to the collision of the Cear? domain of the BP with the West African craton is also correlated with a dipolar gravity anomaly. The positive lobule of this anomaly coincides with the Sobral-Pedro II shear zone whilst the negative lobule is associated with the Santa Quit?ria magmatic arc. Judging by their geophysical signatures, the major BP internal boundaries are: i)the western sector of the Pernambuco shear zone and the eastern continuation of this shear zone as the Congo shear zone, ii) the Patos shear zone, and iii) the Jaguaribe shear zone and its southwestern continuation as the Tatajuba shear zone. These boundaries divide the BP in five tectonic domains in the geophysical criteria: Sul, Transversal, Rio Grande do Norte, Cear?, and M?dio Corea?. The Sul domain is characterized by geophysical signatures associated with the BP and SFP collision. The fact that Congo shear zone is now proposed as part of the Transversal domain boundary implies an important change in the original definition of this domain. The Rio Grande do Norte domain presents a highly magnetized crust resulted from the superposition of precambrian and phanerozoic events. The Cear? domain is divided by the Senador Pompeu shear zone in two subdomains: the eastern one corresponds to the Or?s-Jaguaribe belt and the western one to the Cear?-Central subdomain. The latter subdomain exhibits a positive ENE-W SW gravity anomaly which was associated to a crustal discontinuity. This discontinuity would have acted as a rampart against to the N-S Brasiliano orogenic nappes. The M?dio Corea? domain also presents a dipolar gravity anomaly. Its positive lobule is due to granulitic rocks whereas the negative one is caused by supracrustal rocks. The boundary between M?dio Corea? and Cear? domains can be traced below the Parna?ba basin sediments by its geophysical signature. The joint analysis of free air anomalies, free air admittances, and effective elastic thickness estimates (Te) revealed that the Brazilian East and Equatorial continental margins have quite different elastic properties. In the first one 10 km < Te < 20 km whereas in the second one Te ? 10 km. The weakness of the Equatorial margin lithosphere was caused by the cenozoic magmatism. The BP continental margin presents segmentations; some of them have inheritance from precambrian structures and domains. The segmentations conform markedly with some sedimentary basin features which are below described from south to north. The limit between Sergipe and Alagoas subbasins coincides with the suture between BP and SFP. Te estimates indicates concordantly that in Sergipe subbasin Te is around 20 km while Alagoas subbasin has Te around 10 km, thus revealing that the lithosphere in the Sergipe subbasin has a greater rigidity than the lithosphere in the Alagoas subbasin. Additionally inside the crust beneath Sergipe subbasin occurs a very dense body (underplating or crustal heritage?) which is not present in the crust beneath Alagoas subbasin. The continental margin of the Pernambuco basin (15 < Te < 25 km) presents a very distinct free air edge effect displaying two anomalies. This fact indicates the existence in the Pernambuco plateau of a relatively thick crust. In the Para?ba basin the free air edge effect is quite uniform, Te ? 15 km, and the lower crust is abnormally dense probably due to its alteration by a magmatic underplating in the Cenozoic. The Potiguar basin segmentation in three parts was corroborated by the Te estimates: in the Potiguar rift Te ? 5 km, in the Aracati platform Te ? 25 km, and in the Touros platform Te ? 10 km. The observed weakness of the lithosphere in the Potiguar rift segment is due to the high heat flux while the relatively high strength of the lithosphere in the Touros platform may be due to the existence of an archaean crust. The Cear? basin, in the region of Munda? and Icara? subbasins, presents a quite uniform free air edge effect and Te ranges from 10 to 15 km. The analysis of the Bouguer admittance revealed that isostasy in BP can be explained with an isostatic model where combined surface and buried loadings are present. The estimated ratio of the buried loading relative to the surface loading is equal to 15. In addition, the lower crust in BP is abnormally dense. These affirmations are particularly adequate to the northern portion of BP where adherence of the observed data to the isostatic model is quite good. Using the same above described isostatic model to calculate the coherence function, it was obtained that a single Te estimate for the entire BP must be lower than 60 km; in addition, the BP north portion has Te around 20 km. Using the conventional elastic flexural model to isostasy, an inversion of crust thickness was performed. It was identified two regions in BP where the crust is thickened: one below the Borborema plateau (associated to an uplifting in the Cenozoic) and the other one in the Cear? domain beneath the Santa Quit?ria magmatic arc (a residue associated to the Brasiliano orogenesis). On the other hand, along the Cariri-Potiguar trend, the crust is thinned due to an aborted rifting in the Cretaceous. Based on the interpretation of free air anomalies, it was inferred the existence of a large magmatism in the oceanic crust surrounding the BP, in contrast with the incipient magmatism in the continent as shown by surface geology. In BP a quite important positive geoid anomaly exists. This anomaly is spatially correlated with the Borborema plateau and the Maca?-Queimadas volcanic lineament. The integrated interpretation of geoid height anomaly data, global shear velocity model, and geologic data allow to propose that and Edge Driven Convection (EDC) may have caused the Cenozoic magmatism. The EDC is an instability that presumably occurs at the boundary between thick stable lithosphere and oceanic thin lithosphere. In the BP lithosphere, the EDC mechanism would have dragged the cold lithospheric mantle into the hot asthenospheric mantle thus causing a positive density contrast that would have generated the main component of the geoid height anomaly. In addition, the compatibility of the gravity data with the isostatic model, where combined surface and buried loadings are present, together with the temporal correlation between the Cenozoic magmatism and the Borborema plateau uplifting allow to propose that this uplifting would have been caused by the buoyancy effect of a crustal root generated by a magmatic underplating in the Cenozoic / A Prov?ncia Borborema (PB) ? um dom?nio geol?gico-estrutural localizado no Nordeste do Brasil, limitado a sul pelo Cr?ton do S?o Francisco, a oeste pela Bacia do Parna?ba e a norte e leste pelas bacias costeiras. Embora bastante estudada por geologia de superf?cie, na PB ainda est?o em aberto aspectos importantes de sua evolu??o, notadamente: i) a sua compartimentagem tect?nica ap?s a Orog?nese Brasiliana, ii) a arquitetura da margem continental implantada no Cret?ceo, iii) as propriedades el?sticas de sua litosfera, e iv) as causas do magmatismo e do soerguimento no Cenoz?ico. Esta Tese empregou dados geof?sicos de cobertura regional (eleva??o, gravimetria, magnetometria, altura geoidal e tomografia), para aportar informa??es de geologia profunda aos problemas acima colocados. A sutura gerada pela colis?o neoproteroz?ica entre o Dom?nio Sul da PB e a Placa Sanfranciscana (PSF) ? marcada, na Faixa Riacho do Pontal e no oeste da Faixa Sergipana, por uma forte anomalia gravim?trica dipolar, cujo pico positivo corresponde ao al?amento da crosta inferior da PB e o negativo corresponde ?s nappes de supracrustais empurradas sobre a PSF. Na regi?o leste da Faixa Sergipana n?o h? assinaturas gravim?tricas que indiquem cavalgamento e flexura de placas, mas a interpreta??o de truncamentos de assinaturas geof?sicas de dire??o N-S da PSF permite localizar a sutura na margem sul do complexo de arco Maranc?, ao longo da Z. C. Porto da Folha. Por sua vez, o limite colisional do Dom?nio Cear? da PB com o Cr?ton Oeste-Africano, ao longo da Z. C. Sobral-Pedro II, ? tamb?m marcado por uma anomalia gravim?trica dipolar, cujo pico positivo coincide com a Z. C. Sobral-Pedro II, e o negativo coincide com o arco magm?tico de Santa Quit?ria. A julgar pela express?o geof?sica, os limites internos mais importantes da PB s?o: i) a Z. C. Pernambuco Oeste e sua continua??o na Z. C. Congo, ii) a Z. C. Patos e iii) a Z. C. Jaguaribe e sua continua??o na Z. C. Tatajuba. Estes limites dividem a PB em cinco grandes dom?nios geof?sicos-tect?nicos: Sul (ou Externo), Transversal, Rio Grande do Norte, Cear? e M?dio Corea?. O Dom?nio Sul ? marcado por assinaturas geof?sicas associadas ? colis?o da PB com a PSF. O Dom?nio Transversal teve a sua concep??o original de limites modificada porque a parte leste do seu limite sul foi associada com a Z. C. Congo. O Dom?nio Rio Grande do Norte apresenta a crosta mais magn?tica da PB, com superposi??o de fontes pr?-cambrianas e faneroz?icas. No Dom?nio Cear?, a Z. C. Senador Pompeu ? o divisor de dois subdom?nios: o leste corresponde ? Faixa Or?s-Jaguaribe e o oeste corresponde ao Cear?-Central, onde ocorre uma assinatura gravim?trica interpretada como uma descontinuidade crustal de dire??o ENE-WSW, que funcionou como um anteparo para as nappes brasilanas, com sentido de deslocamento para sul. O Dom?nio M?dio Corea? apresenta uma anomalia gravim?trica dipolar, cujo pico positivo est? associado com rochas granul?ticas, e o negativo com rochas supracrustais. A assinatura geof?sica do seu limite com o Dom?nio Cear? ? evidente, apesar dos sedimentos da Bacia do Parna?ba. A an?lise conjunta da anomalia ar-livre, admit?ncia ar-livre e estimativas da espessura el?stica efetiva (Te) evidenciou que as margens Leste e Equatorial possuem propriedades el?sticas bastante diferentes: enquanto a primeira tem Te entre 10 e 20 km, a segunda tem Te em torno ou inferior a 10 km. Essa diferen?a ? devida ao enfraquecimento da litosfera da Margem Equatorial produzida pelo magmatismo cenoz?ico. A margem continental da PB apresenta segmenta??es que incorporaram heran?as das estruturas e dos dom?nios pr?-cambrianos, que se correlacionam com os limites conhecidos das bacias. Descrevendo de sul para norte, o limite da separa??o da Bacia Sergipe - Alagoas em duas sub-bacias coincide com a sutura entre o Dom?nio Sul da PB e a PSF; as estimativas de Te indicam, concordantemente, que a Sub-bacia Sergipe (Te ? 20 km) se instalou em uma litosfera mais resistente do que a da Sub-bacia Alagoas (Te ? 10 km). Adicionalmente, no interior da crosta da Sub-bacia Sergipe ocorre um grande corpo denso (underplating ou heran?a crustal?) que n?o continua na Sub-bacia Alagoas. A margem da Bacia de Pernambuco (15 < Te < 25 km) apresenta caracter?sticas diferentes das outras bacias costeiras, porque no Plat? de Pernambuco h? duas anomalias do efeito de borda , o que indica a exist?ncia no plat? de uma crosta continental afinada, contudo ainda relativamente espessa. A Bacia da Para?ba se apresenta bastante uniforme, com Te em torno de 15 km, e possui uma crosta inferior relativamente densa, que foi interpretada como uma modifica??o por underplating magm?tico relacionado com o magmatismo cenoz?ico. A segmenta??o da Bacia Potiguar em tr?s partes ? corroborada pelas estimativas de Te: Rifte Potiguar (Te ? 5 km), Plataforma de Aracati (Te ? 25 km) e Plataforma de Touros (Te ? 10 km). A fragilidade da litosfera na regi?o do Rifte Potiguar est? associada com fluxo t?rmico atual alto, e a resist?ncia relativamente maior da Plataforma de Touros pode ser devida a uma crosta arqueana. A margem da Bacia do Cear?, no trecho das sub-bacias Munda? e Icara?, possui anomalia ar-livre uniforme, com Te entre 10 e 15 km. A an?lise da admit?ncia Bouguer revelou que a condi??o isost?tica da PB ? compat?vel com um modelo em que ocorrem carregamentos combinados na superf?cie e na base da crosta, com a carga da base 15 vezes maior que a do topo. Em adi??o, a PB possui uma crosta inferior anormalmente densa. Estas afirma??es s?o especialmente adequadas para a parte norte da PB porque a? a ader?ncia dos dados observados ao modelo ? maior. Para o mesmo modelo isost?tico e usando a fun??o coer?ncia, estimou-se que a Te da PB deve ser inferior a 60 km, embora sua por??o norte tenha Te de apenas 20 km. A invers?o de espessura de crosta, usando o modelo isost?tico com carga apenas na superf?cie, indicou que existem na PB duas regi?es de espessamento: uma abaixo do Planalto da Borborema (de origem cenoz?ica) e a outra no Dom?nio Cear?, sob o arco magm?tico de Santa Quit?ria (vestigial do Pr?-cambriano). Por outro lado, ocorre um afinamento ao longo do Trend Cariri-Potiguar, que representa o registro no interior do continente de um rifteamento cret?ceo abortado. A interpreta??o das anomalias ar-livre de fontes oce?nicas levou ? proposi??o de que ocorreu um volumoso magmatismo na ?rea oce?nica adjacente ? PB, ao contr?rio da ?rea continental, como indicam as informa??es de geologia de superf?cie. A PB apresenta uma expressiva anomalia positiva de ge?ide, com correla??o espacial com o Planalto da Borborema e o Alinhamento Macau-Queimadas. A integra??o de dados de tomografia de ondas superficiais e de anomalias residuais de ge?ide permitiu interpretar que uma convec??o em pequena escala (Edge Driven Convection-EDC), gerada na interface entre a raiz da litosfera continental fria e o manto quente da ?rea oce?nica, pode ter sido a causa do magmatismo cenoz?ico. O mecanismo de EDC teria causado o arrasto do manto litosf?rico continental frio para dentro do manto astenosf?rico quente, ocasionando assim contraste positivo de densidade, que seria uma componente importante da origem da anomalia de ge?ide. A compatibilidade dos dados gravim?tricos da PB com o modelo isost?tico que combina carregamentos no topo e na base da crosta, e a correla??o temporal entre o magmatismo cenoz?ico e o soerguimento do planalto, permite propor que o soerguimento deste ocorreu por causa do empuxo provocado pela raiz da crosta, produzida por um underplating magm?tico no Cenoz?ico
5

Analyse et modélisation du repliement spatial de l'épigénome / Analysis and modelization of the spatial folding of the epigenome

Haddad, Noëlle 17 November 2016 (has links)
L'ADN chromosomique des cellules eucaryotes est fortement condensé au sein d'un complexe nucléoprotéïque, la chromatine. Aussi bien l'organisation spatiale que la composition biochimique (état “épigénomique”) de la chromatine jouent un rôle fondamental dans la régulation des gènes. Grâce aux récents développements des techniques de séquençage à haut-débit, il est possible de déterminer l'état épigénomique local de la chromatine ainsi que la probabilité de contact entre deux sites génomiques (technique dite de “Hi-C”). Ces deux techniques ont permis de mettre en évidence l’existence de domaines d’interaction dont les positions corrèlent fortement avec la segmentation épigénomique de la chromatine. Cependant, les mécanismes responsables de ce couplage sont encore mal compris. L’objectif de cette thèse est de bâtir des modèles physiques permettant de valider l’hypothèse que l’épigénome est un acteur majeur dans le repliement 3D de la chromatine. Pour cela, nous avons tout d’abord développé “IC-Finder”, un algorithme permettant de segmenter les cartes Hi-C en domaines d’interaction. Nous avons alors pu quantifier précisément l’association entre épigénome et organisation de la chromatine. Les corrélations trouvées justifient l’idée de modéliser la chromatine par un copolymère par bloc dont les monomères ont chacun un état épigénomique. Dans ce cadre, nous avons développé une méthode d’inférence des potentiels d'interaction entre sites génomiques à partir des cartes Hi-C expérimentales. Ce travail permettra à plus long terme de prévoir l’organisation de la chromatine sous différentes conditions, ce qui permettra d’étudier en particulier les changements de structure résultant de l’altération de l’épigénome. / DNA of eukaryotes is highly condensed in a nucleoprotein complex called chromatin. Both the spatial organization and the biochemical composition (“epigenomic” state) of the chromatin are fundamental for gene regulation. Remarkably, recent studies indicate that1D epigenomic domains tend to fold into 3D topologically associated domains (TADs) forming specialized nuclear chromatin compartments. In this thesis, we address the question of the coupling between chromatin folding and epigenome. We first built a software called IC-finder to segment HiC maps into interacting domains. We next used it to quantify correlations between the TADs and epigenomic partitions of the genome. This led us to develop a physical model of the chromatin with the working hypothesis that chromatin organization is driven by physical interactions between epigenomic loci. We modeled chromatin as a block copolymer where each block corresponds to an epigenomic domain. With this framework, we developed a method to infer interaction parameters between chromatin loci from experimental Hi-C map. An outcome of such inference process would be a powerful tool to predict chromatin organization in various conditions, allowing investigating in silico changes in TAD formations and long-range contacts when altering the epigenome.

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