La partie ouest du rift de Corinthe, en Grèce, s'ouvre à une vitesse d'environ 15 mm par an générant un taux de déformation parmi les plus élevés au monde, quelques séismes destructeurs de magnitude M>6 par décennie, et une forte activité microsismique irrégulière spatialement et temporellement. Afin de mieux comprendre les mécanismes liés à cette déformation crustale et de préciser les structures majeures actives, ce travail de recherche exploite la base de données sismologiques du Corinth Rift Laboratory de 2000 à 2015 en analysant finement les microséismes et leur évolution spatio-temporelle. La relocalisation globale des sources sismiques ainsi que leur classification en multiplets ont permis de préciser la géométrie des failles et d'identifier des comportements mécaniques différents. La zone ouest, au milieu du golfe, est affectée par des variations de pressions de fluides dans une couche géologique, entraînant des migrations des essaims de microséismes à des vitesses d'environ 50 m par jour. Les multiplets profonds de la partie centrale, près de la côte nord, sont persistants et semblent déclenchés par des épisodes de glissements lents asismiques sur un détachement immature pouvant atteindre la croûte ductile. Le faible pourcentage de déclenchement dynamique par les ondes sismiques suggère que l'état global du système de failles n'est pas au seuil critique de rupture. La magnitude des séismes est corrélée à l'impulsivité initiale de la rupture. Ces résultats précisent la dynamique de déformation du rift, les interactions sismique-asismiques, et permettront d'améliorer les modèles d'aléas sismiques de la région / The western part of the Corinth Rift in Greece is opening at about 15 mm per year, generating one of the highest deformation rates in the world, some destructive earthquakes of magnitude M>6 per decade, and high microseismic activity irregular in space and time. In order to better understand the mechanisms related to this crustal deformation and to specify the major active structures, this research work makes use of the seismological database of the Corinth Rift Laboratory from 2000 to 2015 by finely analyzing microearthquakes and their spatio-temporal evolution. The global relocation of the seismic sources and their classification into multiplets enable to refine the geometry of the faults and to identify different mechanical behaviors. The western zone, in the middle of the gulf, is affected by fluctuations of fluid pore pressures in a geological layer, resulting in microseismic swarm migrations at a velocity of about 50 m per day. The deep multiplets of the central part, near the northern coast, are persistent and appear to be triggered by episodes of slow aseismic slip along an immature detachment, which can reach the ductile crust. The low percentage of dynamic triggering by passing seismic waves suggests that the overall state of the fault system is not at the critical breaking point. The magnitude of earthquakes is correlated with the initial impulsiveness of the rupture. These results specify the dynamics of the rift deformation, the seismic-aseismic interactions, and will make possible the improvement of the seismic hazard models of the region

[Truncated abstract] Self-filtration is here defined as particle detachment and re-deposition causing re-arrangement of the particles and therefore pore space which affects water flow in soil by decreasing hydraulic conductivity. This is of particular important in soils which are susceptible to structural breakdown. The objective of this thesis was to examine the dynamics of the self-filtration process in sodic sandy soils as affected by ionic strength and soil solution composition. The temporal changes of hydraulic conductivity and the elution of fine particles from soil columns were used as the main criteria to assess selffiltration. Two porous media exhibiting significantly different structural cohesion were examined, one a loamy sand (Balkuling soil) from agricultural land use and the second a mining residue from mineral sands operations . . . The effects of the composition of mixed calcium (Ca) and sodium (Na) ions in solution (sodium adsorption ratio (SAR)) on the exchange behaviour and saturated hydraulic conductivity were examined by carrying out batch binary exchange and saturated column transport experiments. A strong preference for Ca2+ ions in the exchange complex was observed for both soils. Generally K/Ko was found to decrease with increasing sodium adsorption ratio with the more structured Balkuling soil maintaining K/Ko for SARs 3 and 5 at an electrolyte concentration of 100 mmol/L. However measurements at the critical threshold and turbidity concentrations at a SAR of 15 revealed structural breakdown of the pore matrix system attributed to various extents of slaking, swelling, dispersion and decreases of pore radii as a result of selffiltration during leaching. These experiments illustrate the wide range of complex interactions involving clay mineralogy, solution composition and structural factors which can influence the extent of mobilization, transport and re-deposition of colloidal particles during the leaching process in soil profiles.

[pt] Esta tese propõe uma metodologia de estimativa de pressão de poros em rochasreservatório através dos atributos sísmicos velocidade compressional V(p) e velocidade cisalhante V(s). Na metodologia, os atributos são encarados como observações realizadas sobre um sistema físico, cujo comportamento depende de um determinado número de grandezas não observáveis, dentre as quais a pressão de poros é apenas uma delas. Para estimar a pressão de poros, adota-se uma abordagem Bayesiana de inversão. Através de uma função de verossimilhança, estabelecida através de um modelo de física de rochas calibrável para a região, e do teorema de Bayes, combina- se as informações pré-existentes sobre os parâmetros de rocha, fluido e estado de tensões com os atributos sísmicos observados, inferindo probabilisticamente a pressão de poros. Devido a não linearidade do problema e ao interesse de se realizar uma rigorosa análise de incertezas, um algoritmo baseado em simulações de Monte Carlo (um caso especial do algoritmo de Metropolis- Hastings) é utilizado para realizar a inversão. Exemplos de aplicação da metodologia proposta são simulados em reservatórios criados sinteticamente. Através dos exemplos, demonstra-se que o sucesso da previsão de pressão de poros depende da combinação de diferentes fatores, como o grau de conhecimento prévio sobre os parâmetros de rocha e fluido, a sensibilidade da rocha perante a variação de pressões diferenciais e a qualidade dos atributos sísmicos. Visto que os métodos existentes para previsão de pressão de poros utilizam somente o atributo V(p) , a contribuição do atributo V(s) na previsão é avaliada. Em um cenário de rochas pouco consolidadas (ou em areias), demonstra-se que o atributo V(s) pode contribuir significativamente na previsão, mesmo apresentando grandes incertezas associadas. Já para um cenário de rochas consolidadas, demonstra-se que as incertezas associadas às pressões previstas são maiores, e que a contribuição do atributo V(s) na previsão não é tão significativa quanto nos casos de rochas pouco consolidadas. / [en] This work proposes a method for pore pressure prediction in reservoir rocks through compressional- and shear-velocity data (seismic attributes). In the method, the attributes are considered observations of a physic system, which behavior depends on a several not-observable parameters, where the pore pressure is only one of these parameters. To estimate the pore pressure, a Bayesian inversion approach is adopted. Through the use of a likelihood function, settled through a calibrated rock physics model, and through the Bayes theorem, the a priori information about the not-observable parameters (fluid and rock parameters and stress state) is combined with the seismic attributes, inferring probabilistically the pore pressure. Due the non-linearity of the problem, and due the uncertainties analysis demanding, an algorithm based on Monte Carlo simulations (a special case of the Metropolis- Hastings algorithm) is used to solve the inverse problem. The application of the proposed method is simulated through some synthetic examples. It is shown that a successfully pore pressure prediction in reservoir rocks depends on a set of factors, as how sensitive are the rock velocities to pore pressure changes, the a priori information about rock and fluid parameters and the uncertainties associates to the seismic attributes. Since the current methods for pore pressure prediction use exclusively the attribute compressional velocity V(p), the contribution of the attribute shear velocity V(s) on prediction is evaluated. In a poorly consolidated rock scenario (or in sands), the V(s) data, even with great uncertainties associated, can significantly contribute to a better pore pressure prediction. In a consolidated rock scenario, the uncertainties associated to pore pressure estimates are higher, and the s V data does not contribute to pore pressure prediction as it contributes in a poorly consolidated rock scenario.

Ce travail est motivé par la nécessité de mieux comprendre la technique de récupération du pétrole par injection de polymères à l'échelle du pore. On considère deux fluides immiscibles dans un réseau de microcanaux. A cette échelle, le diamètre des canaux est de l'ordre de quelques dizaines de micromètres tandis que la vitesse est de l'ordre du centimètre par seconde. Cela nous permet d'utiliser les équations de Stokes incompressible pour décrire l'écoulement des fluides. Le modèle Olroyd-B est utilisé pour décrire l'écoulement du fluide viscoélastique. Afin d'effectuer des simulations numériques dans une géométrie complexe comme un réseau de microcanaux, une méthode de pénalisation est utilisée. Pour suivre l'interface entre les deux fluides, la méthode Level-Set est employée. Le modèle pour la dynamique de la ligne triple est basé sur les la loi de Cox. Enfin, on présente des résultats de simulations numériques avec des paramètres physiques réalistes. / This work is motivated by the need for better understanding the polymer Enhanced Oil Recovery (EOR) technique at the pore-scale. We consider two phase immiscible fluids in a microchannel network. In microfluidics, the diameter of the channels is of the order of a few tens of micrometers and the flow velocity is of the order of one centimeter per second. The incompressible Stokes equations are used to describe the fluid flow. The Oldroyd-B rheological model is used to capture the viscoelastic behavior. In order to perform numerical simulations in a complex geometry like a microchannel network, a penalization method is implemented. To follow the interface between the two fluids, the Level-Set method is employed. The dynamic contact line model used in this work is based on the Cox law. Finally, we perform simulations with realistic parameters.

Pore forming toxins are known for their ability to efficiently form transmembrane pores which eventually leads to cell lysis. PFTs have potential applications in devel-oping novel drug and gene delivery strategies. Although structural aspects of many pore forming toxins have been studied, very little is known about the dynamics and subsequent rupture mechanisms. In the first part of the thesis, a combined experimental and modeling study to understand the lytic action of Cytolysin A (ClyA) toxins on red blood cells (RBCs) has been presented. Lysis experiments are carried out on a 1% suspension of RBCs for different initial toxin concentrations ranging from 100 – 500 ng/ml and the extent of lysis is monitored spectrophotometrically. Using a mean field approach, we propose a non – equilibrium adsorption-reaction model to quantify the rate of pore formation on the cell surface. By analysing the model in a pre-lysis regime, the number of pores per RBC to initiate rupture was found to lie between 400 and 800. The time constants for pore formation are estimated to lie between 1-25 s and monomer conformation time scales were found to be 2-4 times greater than the oligomerization times. Using this model, we are able to predict the extent of cell lysis as a function of the initial toxin concentration. Various kinetic models for oligomerization mechanism have been explored. Irreversible sequential kinetic model has the best agreement with the available experimental data. Subsequent to the mean field approach, a population balance model was also formulated. The mechanics of cell rupture due to pore formation is poorly understood. Efforts to address this issue are concerned with understanding the changes in the membrane mechanical properties such as the modulus and tension in the presence of pores. The second part of the thesis is concerned with using atomic force microscopy to measure the mechanical properties of cells. We explore the possibility of employing tapping mode AFM (TM-AFM) to obtain the elastic modulus of soft samples. The dynamics of TM-AFM is modelled to predict the elastic modulus of soft samples, and predict optimal cantilever stiffness for soft biological samples. From experiments using TM-AFM on Nylon-6,6 the elastic modulus is predicted to lie between 2 and 5 GPa. For materials having elastic moduli in the range of 1– 20 GPa, the cantilever stiffness from simulations is found to lie in the range of 1 – 50 N/m. For soft biological samples, whose elastic moduli are in the range of 10-1000 kPa, a narrower range of cantilever stiffness (0.1 – 0.6 N/m), should be used.

Le pore de transition de perméabilité mitochondriale (PTPm) joue un rôle majeur dans la mort cellulaire et dans la cardioprotection. Notre hypothèse est que le complexe I de la chaîne respiratoire est impliqué dans la régulation de l’ouverture du PTPm. Sur des mitochondries isolées de cœurs des rongeurs, nous avons pu démontrer que le PTPm est désensibilisé par la cyclosporine A, un inhibiteur de la cyclophiline D (CyP-D), et cet effet est largement amplifié en présence de la roténone, un inhibiteur du complexe I. Ces résultats ont été confirmés chez la souris CyP-D déficiente. L’étude de plusieurs types cellulaires a aussi confirmé l’effet de la roténone dans la régulation du PTPm. Ainsi, nous avons pu montrer que le flux d’électrons travers le complexe I est capable de réagir sur un site de régulation du PTPm cardiaque masqué par la CyP-D. De plus, les analogues de l’ubiquinone, élément de la chaîne respiratoire impliqué dans le transfert d’électrons entre les complexes I, II et III, modulent la susceptibilité du PTPm vis-à-vis du Ca2+. Par ailleurs, dans un modèle de cœur isolé du rat, le postconditionnement par le perindoprilate, un inhibiteur de l’enzyme de conversion, diminue la taille de l’infarctus après l’ischémie-reperfusion d’une façon NO-dépendant. L’ensemble de nos résultats ouvre de nouvelles perspectives thérapeutiques dans la cardioprotection et montre l’importance du complexe I et de la CyP-D comme cibles moléculaires incontournables dans la cardioprotection / The mitochondrial permeability transition pore (mPTP) plays an important role in cell death and cardioprotection. Our hypothesis is that the complex I of mitochondrial respiratory chain regulates the opening of mPTP. We showed that the opening of mPTP was inhibited by Cyclosporin A (CsA), a cyclophilin D (CyP-D) inhibitor, in mitochondria isolated from rodent heart, and this effect was largely amplified by rotenone, a complex I inhibitor. These results were confirmed in mitochondria devoid of CyP-D. A study realised in several cell lines also confirmed the effect of rotenone in mPTP regulation. We concluded that the electron flow through the respiratory chain complex I regulate mPTP opening and the regulatory site is masked by CyP-D in cardiac mitochondria. Moreover, two analogues of ubiquinone, mobile carrier of electrons between complex I, II and complex III, modulate the susceptibility of mPTP. In addition, in a model of isolated rat heart, postconditioning with Perindoprilat, an angiotensin converting enzyme inhibitor, protects the heart from ischemia-reperfusion injury in an NO-dependant manner. The findings of the present work put new therapic perspectives in cardioprotection

L'étude du comportement du béton en température est un problème majeur qui vise in fine à évaluer le niveau de sécurité des structures sous des sollicitations thermiques sévères, lors d'incendies par exemple. Pour cela, de nombreux modèles sont développés dans un cadre de couplage thermo-hydro-mécanique (THM), pour prendre en compte les différents processus physico-chimiques et mécaniques mobilisés par ces sollicitations et conditionnant la stabilité du matériau béton.Cependant, ces modélisations ne prennent souvent pas en compte explicitement la nature hétérogène du matériau. En effet, le béton est un matériau constitué d'inclusions noyées dans une matrice cimentaire pouvant être schématisée comme un milieu poreux ouvert partiellement saturé en eau. Les inclusions sont caractérisées par leurs natures minéralogiques, leurs morphologies et leurs tailles classées en fuseaux granulaires. Cette hétérogénéité introduit une complexité supplémentaire : la nécessité de prendre en compte la microstructure pour quantifier l'effet de l'incompatibilité (thermique, hydrique et mécanique) inclusion-matrice sur le comportement THM du béton. Ce travail constitue une première avancée dans ce sens. A ce titre, une modélisation élément fini multi-échelle tridimensionnelle (3D) est développée permettant d'affecter des comportements spécifiques à la matrice et aux inclusions. Pour la matrice, siège des transports de masse dans son réseau poreux connecté, une approche thermo-hydrique à trois fluides (eau, vapeur et air sec) est adoptée et est couplée à une loi de comportement poro-mécanique endommageable. Les inclusions (granulats) sont considérées hydriquement inertes, une approche thermo-mécanique avec endommagement est alors retenue.Une analyse, par simulations numériques, des effets de la nature minéralogique des granulats (calcaires ou silico-calcaires) de leurs distributions et de leurs morphologies a été menée sur des configurations 2D et 3D. Les effets étudiés ont notamment concerné l'influence de ces paramètres sur les fluctuations locales des champs de température, de pression de gaz et d'endommagement au regard de la dispersion des mesures expérimentales. L'analyse est limitée à l'échelle mésoscopique, celle où les granulats de taille caractéristique supérieure à 5 mm sont considérés, le reste (stable et pâte de ciment) étant une matrice homogène. Enfin, cette analyse a mis en évidence le besoin de mettre en œuvre une approche expérimentale cohérente avec une analyse mutli-échelle, à la fois pour la caractérisation des propriétés (thermiques, hydriques et mécaniques) de chaque constituant et pour l'étude des évolutions des champs lors des changements d'échelles. Un protocole expérimental a été définit et des premiers résultats d'essais sont présentés et analysés au travers de résultats obtenus dans la partie modélisation / The investigation of the behavior of heated concrete is a major research topic which concerns the assessment of safety level of structures when exposed to high temperatures, for instance during a fire. For this purpose, several modeling approaches were developed within thermo-hydro-mechanical (THM) frameworks in order to take into account the involved physic-chemical and mechanical processes that affect stability of heated concrete. However, existing models often do note account explicitly for the heterogeneity of the material : concrete is composite material that may be schematized as an assembly of inclusions (aggregates) embedded in a cementitious matrix (cement paste). This latter may be described as a partially saturated open porous medium. The aggregates are characterized by their mineralogical nature together with their morphology and size distribution. The material heterogeneity bring an additional complexity : the need to take into account the microstructure in order to quantify the effect of matrix-inclusion thermal, hygral and mechanical incompatibilities on the THM behavior of concrete. This work is a first step in this direction. For this purpose, a three-dimensional (3D) multi-scale finite element model is developed. It allows affecting specific behaviors to matrix and inclusions. For the former, where mass transports occur within the connected porous network, a three-fluids approach (liquid water, vapor and dry air) is adopted and is coupled to a poro-mechanical damage based approach. For inclusions (aggregates) no hygral component arises a pure thermo-mechanical model is considered. The developed model is then used to investigate, either by 2D or 3D numerical simulations, effects of mineralogical nature, morphology and distribution of aggregates. Studied effects have mainly concerned the influence of these parameters on local fluctuations of simulated temperature, gas pressure and damage fields with regard to experimentally observed dispersion. The analysis is here limited to the mesoscale, at which only aggregates with a characteristic size above 5 mm are meshed while the remaining inclusions together with the cement paste are considered to be a homogeneous matrix. Finally, the numerical analysis carries out the need to perform an experimental campaign that is consistent with a multi-scale approach of the THM behavior of concrete : an experimental campaign that allows to identify thermal, hygral and mechanical properties of each concrete constituent and that permit to assess evolution of fields during upscalling. An experimental protocol is then elaborated for this purpose and some obtained results are presented and analyzed with regard to results obtained in the modeling part

La translocation de biopolymères à travers un nanopore intervient dans de nombreux processus biologiques et technologiques, comme le transport nucléocytoplasmique dans le pore nucléaire des cellules eucaryotes, la sécrétion de protéines, le séquençage rapide de l’ADN ou l’électrophorèse capillaire.Nous proposons une technique optique en molécule unique originale pour l’étude de la translocation de biopolymères à travers un nanopore basée sur l’effet Zero-Mode Waveguide. Nous nous sommes intéressés au passage d’ADN double-brin de plusieurs tailles, d’ADN simple-brin et d’ARN, entraînés par un flux à travers une membrane nanoporeuse track-etched. Nous montrons qu’il existe un flux critique régissant le passage des biopolymères indépendant du rayon des pores ainsi que de la taille des biopolymères et de leur nature, conformément aux prédictions théoriques de Brochard et de Gennes.Le pore nucléaire est un nanopore biologique responsable du transport sélectif entre le noyau et lecytoplasme des cellules. Nous avons étudié l’influence de la concentration en importinBeta1 – une protéine nécessaire au transport nucléocytoplasmique – sur l’organisation du canal central du pore nucléaire deXenopus laevis en mesurant la diffusion de molécules de Dextran fluorescentes à travers celui-ci. Nous observons une ouverture du canal central à basse concentration suivi d’un rétrécissement de celui-ci à plus forte concentration. Cette évolution du rayon du canal central avec la concentration en importin Beta1est conforme aux modèles en champ moyen de Opferman et coll. et de Ando et coll. et aux observations expérimentales sur des systèmes reconstitués in vitro de Lim et coll. et Zahn et coll. / The translocation of biopolymers through a nanopore is a feature common to many biological andtechnological processes such as the nucleocytoplasmic transport through the nuclear pore complex(NPC), protein secretion, fast DNA sequencing or capillary electrophoresis.We have developed an original single molecule optical detection technique for the study of biopolymerstranslocation through a nanopore based on the Zero-Mode Waveguide effect. We studied thepassage of double stranded DNA of different sizes, of single stranded DNA and of double-stranded RNAdriven by a flux through track-etched nanoporous membranes. We demonstrate that translocation isgoverned by a critical flux independent of both biopolymer size and nature and of the pore radius inagreement with the theoretical predictions of Brochard and de Gennes.The NPC is a biological nanopore responsible for the selective transport between cytoplasm andnucleus in cells. We studied the influence of importinBeta1 concentration – a protein involved in the nucleocytoplasmictransport – on the structure of the central channel of the NPC of Xenopus laevis byassessing the diffusion of fluorescently labeled Dextran molecules through the NPC. We observe anopening of the central channel at low concentration followed by a shrinking at higher concentrationin importinBeta1 in agreement with mean-field models from Opferman et al. and Ando et al. and withexperiments on biomimetic in vitro systems from Lim et al. and Zahn et al.

<p> We developed some universal platforms to overexpress the minimal functional entities of ion channels. The modular property of ion channels have been demonstrated from many aspects, such as crystal structures, chimeric channel experiments and discovery of similar modules in distantly related protein families. Thus it should be feasible to express each module independent of other channel modules. The pore-forming module of ion channels has multiple important properties as selectivity, conductivity and drug-binding. If it can be overexpressed, it will provide valuable information about channel selectivity to different ions and structural bases for drug binding as well as important application in drug screening and rational drug design. </p> <p> To test this, we first used the model channel KcsA to identify the minimal requirements for a pore-forming domain to functionally exist independently. Chapter 2 of this thesis explains in detail how the wild type C-terminal cytoplasmic domain of KcsA functions. We found that this domain has dual function as pH-sensor and tetramerization domain, and it is essential for the expression of the pore-forming domain of KcsA. Once we knew the physiological role of the cytoplasmic domain, the scenario was set to answer the question of how to make it better for the application of structural and functional studies. </p> <p> In chapter 3 and chapter 4, we replaced the wild type C-terminal domain with non-native tetramerization domains. We identified the direct correlation between protein expression level and overall thermostability of pore-forming domains. The C-terminal tetramerization domains stabilize channels in a cooperative way and play a critical way in in vivo channel assembly. The selection of the linker between pore-forming domain and tetramerization domain, the splicing motif, and the handedness of C-terminal tetrameric coiled coils all affect channel expression level and stability. </p> <p> We applied our finding in KcsA to a wide range of ion channels in chapter 5, including voltage-gated potassium channels, Ca2+-gated potassium channels, inwardrectifying potassium channels, cyclic nucleotide-gated potassium channels and voltagegated sodium channels. We managed to express similar minimal structural modules from these more structurally complicated channels with the assistance of different cytoplasmic tetramerization domains. Several minimal channels expressed well and showed similar biophysical and functional property as the wild type channels. </p> <p> These studies demonstrate that the pore-forming modules of ion channels can be expressed independently while retaining the proper structure and drug-binding properties as their wild type predecessors when using our universal expression platform. The potential application in structural studies and drug-screening is promising. </p> / Thesis / Doctor of Philosophy (PhD)

Le complexe de pores nucléaires est le seul point d'entrée et de sortie du transport nucléocytoplasmique. Le panier nucléaire, l'un de ses principaux composants, s'est avéré impliqué dans la régulation des gènes et pourrait jouer un rôle majeur dans le contrôle de la qualité de l'export d'ARNm. Cependant, on sait peu de choses sur le fonctionnement du panier dans l'export nucléaire et la régulation des gènes. La principale composante structurelle du panier, la TPR (Translocated Promoter Region), est considérée comme l'acteur principal de la fonction de contrôle de la qualité du panier. Il reste à établir par quel mécanisme cette protéine assure la sélection des mRNP compétentes pour l'exportation. Malgré son implication connue dans le contrôle de la qualité des mRNP, l'exportation et la maturation, des questions demeurent: que fait vraiment le panier, qu'est-ce qui définit le contrôle qualité, comment le panier nucléaire est-il capable d'identifier l'ARN qui n'est pas compétent pour l'exportation et quels sont les rôles de différentes protéines composant le panier nucléaire. Récemment, il a été montré que la protéine TPR est présente dans deux populations, l'une dans le nucléoplasme et l'autre liée au NPC. Nos études préliminaires utilisant FRAP (Fluorescence Recorvery After Photobleaching) et la microscopie à molécule unique montrent que les molécules nucléoplasmiques de TPR ne sont pas impliquées dans un échange rapide avec les molécules assemblant avec les paniers ancrés au NPC et présentent différentes sous-populations basées sur la diffusion. L'analyse de études protéomiques préliminaires de notre laboratoire a révélé que l’interactome de TPR présente un enrichissement inattendu en protéines impliquées dans la maturation de l'ARNm, notamment l'épissage et les facteurs de traitement de l'extrémité 3'. Ces résultats pourraient suggérer des interactions complexes des nouvelles fractions nucléoplasmiques de TPR avec la machinerie de maturation des ARNms et nous amènent à poser les questions suivantes : Quelle est la fonction de la protéine du panier TPR lorsqu'elle n'est pas associée au NPC, et la TPR nucléoplasmique participe-t-elle au métabolisme de l'ARN nucléaire, reliant potentiellement les processus nucléaires au contrôle de la qualité au NPC? Mon projet s'est concentré sur l'étude des fonctions et de la dynamique de la protéine du panier nucléaire TPR à l'aide de techniques d'imagerie fluorescente en cellule vivante et de suivi de protéine unique. Nous avons pu identifier la dynamique et la localisation des différentes populations de TPR à partir des profils de diffusion de leurs trajectoires, qui peuvent être réparties en 5 catégories : Dirigée, Brownienne, Restreinte, Confinée et Butterfly. Nos données suggèrent que les trajectoires confinées pourraient être liée à l’association de TPR à la chromatine tandis que les browniennes représenteraient les molécules de TPR diffusant librement dans le noyau. De plus, nous avons constaté que les trajectoires dirigées et restreintes pourraient être liées à la maturation de l'ARN vu que ces deux sous-populations de TPR sont les plus affectées lorsque la transcription est inhibée. Également, en absence de la transcription par l’ARN polymérase II, TPR forme des granules dans le nucléoplasme, suggérant son implication durant la transcription active. Ainsi, notre étude montre que la fraction nucléoplasmique du TPR est subdivisée en fractions non associées aux pores hétérogènes qui pourraient jouer plusieurs rôles dans le métabolisme de l'ARN et la qualité de l'export. / The nuclear pore complex is the only entry and exit point for the nucleocytoplasmic transport. The nuclear basket, one of its main components, was shown to be involved in gene regulation and could play a major role in quality control of mRNA export. However, little is known on how the basket functions in nuclear export and gene regulation. The main structural component of the basket, TPR (Translocated Promoter Region), is thought to be the main actor in the quality control function of the basket. It is yet to be establish by which mechanism this protein ensures the selection of competent mRNPs for export. With all these involvement of the basket in quality control, export, and maturation, one question remains: What is the basket really doing, what defines quality control, how the nuclear basket can identify RNAs that aren’t competent for export, and what are the roles of the different proteins that make up the basket. Recently it was shown that TPR is present in two populations, one in the nucleoplasm and another bound at the NPC. Our preliminary studies using FRAP (Fluorescence Recovery After Photobleaching) and single molecule microscopy shows that the nucleoplasmic TPR molecules aren’t exchanging with the baskets anchored at the NPC and present different subpopulations based on diffusion. Analysis of preliminary proteomics studies from our laboratory revealed an interactome with an unexpected enrichment of proteins involved in mRNA maturation notably splicing and 3’ end processing factors. These results imply complex interactions of the new fractions of TPR and lead us to ask these following questions: What is the function of the basket protein TPR when it is not associated with the NPC, and does nucleoplasmic TPR participate in nuclear RNA metabolism, potentially linking nuclear processes to quality control at the NPC? My project focused on investigating the functions and dynamics of the nuclear basket protein TPR using fluorescent live-cell and single-protein imaging techniques. We were able to identify the dynamics and localization of the different populations of TPR based on the diffusion profiles of their trajectories, which can be divided in 5 categories: Directed, Brownian, Restricted, Confined and Butterfly. Our data suggest that the confined population might be linked to chromatin association of TPR, whereas the Brownian would represent the free diffusing TPR molecules in the nucleus. We further found that the Directed and Restricted trajectories could be linked to RNA maturation as these two subpopulations of TPR are most affected when transcription is inhibited. Moreover, in absence of transcription, TPR forms granules in the nucleus, suggesting its implication during active transcription. Altogether, our study shows that the nucleoplasmic fraction of TPR is subdivided in heterogenous diffusive fractions that could play several roles in the metabolism of RNA and quality of export