WorldCat Identities

École doctorale Frontières de l'innovation en recherche et éducation (Paris / 2006-....).

Overview
Works: 149 works in 157 publications in 2 languages and 158 library holdings
Roles: Other, Degree grantor, 996
Publication Timeline
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Most widely held works by École doctorale Frontières de l'innovation en recherche et éducation (Paris / 2006-....).
Yeast pathology : a systemic analysis of death and aging in budding yeast by Tamara Milošević( Book )

2 editions published in 2011 in English and held by 3 WorldCat member libraries worldwide

Le vieillissement et la mort font partie intégrante de la vie et jouent un rôle dans l'histoire de vie d'un organisme en influençant à la fois la structure de sa population et son évolution. Le vieillissement chez la levure a été largement étudié en observant l'espérance de vie réplicative et chronologique, alors que la mort a été décrite comme un processus similaire à la nécrose et l'apoptose. Malgré le fait que le vieillissement entraîne la mort, les organismes peuvent aussi mourir prématurément à la suite de maladies. Afin de comprendre l'étendue des changements morphologiques précédant la mort, j'ai analysé l'ensemble des 1091 mutants de gènes essentiels de la levure au niveau cellulaire. J'ai décrit de manière quantitative le caractère essentiel de chaque gène et documenté les caractéristiques phénotypiques des cellules et colonies comme une représentation vivide des changements cellulaires chez des mutants de levures avant qu'ils ne cessent de se diviser puis qu'ils ne meurent. Bien que certains phénotypes de mutants de gènes essentiels puissent être expliqués au moyen des connaissances actuelles sur les gènes en question, la complexité des modèles de mort nous montre que la mort à l'échelle cellulaire unique est très peu comprise. Néanmoins il est clair que chez la levure les symptômes résultant d'une maladie génétique diffèrent de ceux résultant du vieillissement normal de la cellule. Ce travail de recherche montre ainsi l'importance des analyses au niveau de la cellule unique de phénomènes complexes biologiques et offre un point de départ pour une exploration future des maladies endogènes et des mécanismes liés au vieillissement entraînant la mort
Le rôle des vésicules extracellulaires dans la capacité invasive du cancer du sein : les fonctions de la famille des facteurs de transcription NFAT = Extracellular vesicles in breast cancer invasiveness : roles of the NFAT family of transcription factors by Lívia Cardoso Bueno de Camargo( Book )

2 editions published in 2016 in English and held by 2 WorldCat member libraries worldwide

Les vésicules extracellulaires (EVs) sont des importants moyens de communication cellulaire, permettant l'échange intercellulaire des mARNs, microARNs et des protéines, parmi d'autres molécules. Depuis quelques années leur rôle dans le développement du cancer est de plus en plus étudié et leur importance dans ce contexte reconnue. Dans le travail présenté ici, nous nous sommes investis dans l'étude du rôle des EVs dans l'établissement des profils d'invasion des lignées de cellules du cancer du sein. Nous nous sommes particulièrement intéréssés à la possibilité que les effets opposés sur la motilité cellulaire des cellules du cancer du sein exercés par NFAT1/NFAT5 et NFAT3 (membres de la famille de facteurs de transcription Nuclear Factor of Activated T Cells) puissent être liés au rôle des EVs dans le contrôle de l'invasion cellulaire. D'une part, NFAT1 et NFAT5 sont exprimés par des lignées fortement invasives du cancer du sein, qui n'expriment pas le récepteur alpha de l'cestrogène (ER alpha -). D'autre part, NFAT3 est exprimé par des lignées moins agressives, qui sont ER alpha+. Pour étudier le possible transfert de ces effets opposés de NFAT par les EVs, nous avons effectué le traitement de cellules fortement invasives (MDA-MB 231) avec des EVs isolées à partir des cellules faiblement invasives (T47D) et vice-versa. Nous avons pu observer que les EVs secrétées par les MDA-MB 231 ont induit une augmentation de l'invasivité des T47D. Inversement, les EVs isolées à partir de T47D ont réduit l'invasivité des MDA-MB 231. De plus, l'expression de NFAT3 chez les T47D est essentielle pour que la réduction d'invasivité puisse avoir lieu, puisque son inhibition dans ces cellules produit des vésicules incapables de promouvoir la réduction d'invasivité. Nous avons aussi démontré que les EVs originaires des T47D induisent la transcription active de TGFbetal chez les MDA-MB 231 qui les reçoivent. Cette augmentation dans les taux de TGFbetal dans la cellule réceptrice est aussi essentielle pour la réduction de la mobilité cellulaire. Ces résultats ont aussi été étendus in vivo où les EVs de T47D (utilisés dans le traitement des souris nude dans lesquelles des cellules humaines MDA MB 231 D3H2LN ont été injectées dans le coussinet adipeux mammaire) réduisent la taille de la tumeur primaire et la formation des métastases d'une façon dépendante de l'expression de NFAT3 chez les cellules productrices d'EVs. Les niveaux sériques de TGFbetal ont aussi augmenté chez les souris où le traitement a été efficace, ce qui fait de cette molécule un bon candidat pour le suivi de l'efficacité du traitement. Nos résultats suggèrent que les EVs representent un possible moyen d'inhibiton de l'invasion des cellules agressives du cancer du sein, et peuvent donc être une option attrayante pour diminuer la progression tumorale chez les patients de cette maladie
Sex-pheronome representation in the moth olfactory pathway : from data analysis to model by Alexandre Grémiaux( Book )

2 editions published in 2011 in English and held by 2 WorldCat member libraries worldwide

This work aims at identifying, quantifying and interpreting the transformations from first- t second-order sensory neurons of the sex pheromone signal in the moth Agrotis ipsilon. First, we analysed statistically single-unit electrophysiological recordings from olfactory receptor neurons (ORNs, first order) stimulated with different doses of the major compound of the sex pheromone blend, which allowed us to reconstruct the sex pheronome input to the olfactory system. Second, we did the same analysis on projection neurons (PNs, second order) stimulated in the same way. Third, we described the signal transformation from ORNs to PNs in terms of firing rates and response latencies. Fourth, we developed a model of the neural network connecting ORNs and PNs accounting for the observed transformations. In addition, we contributed to a review summarizing the chemotransduction models in ORNs another review on information processing in two first layers of the olfactory system
Developing new tools and platforms for mammalian synthetic biology : From the assembly and chromosomal integration of complex dna circuits to the engineering of artificial intercellular communication systems = Développement de nouveaux outils et plate-formes pour la biologie de synthèse mammifère by Xavier Duportet( Book )

2 editions published in 2014 in English and held by 2 WorldCat member libraries worldwide

Mammalian synthetic biology may provide novel therapeutic strategies, help decipher new paths for drug discovery and facilitate synthesis of valuable molecules. Yet, our capacity to program cells is currently hampered both by the lack of efficient approaches to streamline the design, construction and screening of synthetic gene networks, and also by the complexity of mammalian systems and our poor understanding of cellular processes contextƠdependencies. To address these problems, I proposed and validated a number of concepts and approaches during my PhD. First, I created a framework for modular and combinatorial assembly of functional (multi)gene expression vectors and their efficient and specific targeted integration into a well-defined chromosomal context in mammalian cells. Second, I developed a platform to identify and characterize new serine reconnbinase systems from Mycobacteriophage genomes in order to extend the toolbox of genome engineering techniques available for mammalian cells progranning. To overcome the apparent limitations in our single-tell rational engineering capacity, I also engineered two new artificial intercellular communication systems for mammalian cells, in order to facilitate the spatial decoupling of different modules of a synthetic circuit. Even though we are still years away from therapies using engineered cells carrying synthetic circuits to repair damaged or non-functional organs or to create de-novo tissues, I believe the contributions developed during the course of my PhD could potentially be used to help fasten the development of therapeutically relevant DNA circuits or to provide new means to understand mechanisms of cellular processes
Living in a fluid-dynamical landscape : how do marine predators respond to turbulence? by Alice Della Penna( Book )

2 editions published in 2016 in English and held by 2 WorldCat member libraries worldwide

Marine top predators play a fundamental role in maintaining the structure and functioning of healthy marine ecosystems. In the last decades the development of bio-Iogging (i.e. deployment of autonomous recording tags on free-living animals) has radically changed the study of top predators and their interactions with their environment. Combinations of sensors measuring position (Argos and GPS), environmental properties (water temperature, light) and proxies for foraging behavior (accelerometers) have enabled relating migrations of large fish, marine mammals, sea turtles and seabirds to basin scale patterns of ocean currents, temperature, and productivity. However, what influences marine predators' movement at smaller spatial and temporal scales, such as the ones they experience during their foraging trips, is still largely unknown. This project analyses the interaction between marine top predators (elephant seals and macaroni penguins) and sub-mesoscale (few days-months, 10-100 km) ocean dynamics. This is achieved by combining in-situ observations, bio-logging data, remote-sensing, ecological modelling and a Lagrangian approach (i.e. based on the tracking of water parcels). The study is conducted in the sub-Antarctic region around the Kerguelen Plateau (Indian Sector of the Southern Ocean)
How do ecological and evolutionary dynamics interact together and with the environment to shape the structure of oceanic plankton communities? : a modelling approach by Boris Sauterey( Book )

2 editions published in 2014 in English and held by 2 WorldCat member libraries worldwide

Recent global ocean circulation models integrate phytoplankton ecology in a relatively detailed manner, accounting for a variety of plankton functional types or even species-level variability (Follows et al. 2007). Such models have demonstrated the importance of ecological detail (in terms of functional composition) for global biogeochemical cycles and possible positive feedbacks between marine ecosystems and climate change (Cermeho and Falkowski 2009). An open question today is : does phytoplankton (and zooplankton) evolution accelerate or mitigate the impact of climate change on the global carbon cycle? Answering this question is beyond the scope of this thesis, and the work in this thesis should be seen as a first step in this direction. Before being able to answer to the above question, a more fundamental topic needs to be addressed: how do evolution and ecology interact to shape the ecological communities living in the highly complex and temporally forced environment that is the ocean? And a derived, more applied question is: can we obtain a plausible description of the complex food webs in such contexts, without accounting for evolution? Otherwise stated, how reliable is the currently used methodology for simulating the emergence of complex food webs through community assembly, based on the non-adaptive paradigm of "everything is everywhere, but the environment selects"? In order to answer these questions, the more specific objective of my thesis is to extend an existing global circulation model (the MITgcm, Follows et al. 2007; Ward et al. 2012, 2013) in order to allow for the simulation of adaptation of phytoplankton traits
Dynamics and physical properties of the chromatin after DNA damage = Dynamique et propriétés physiques de la chromatine après dommages à l'ADN by Sébastien Herbert( Book )

2 editions published in 2014 in English and held by 2 WorldCat member libraries worldwide

During the last decade, organization and mobility of the chromatin have emerged as major epigenetic factors. They affect and are affected by a number of fundamental biological mechanisms such as gene expression and double¬strand breaks (DSB). For this project, we chose the eukaryotic unicellular Saccharomyces cerevisiae as a model organism because of its relatively simple nuclear structure, simplified genetic engineering and large bibliographie database. Moreover, the small dimensions of the budding yeast facilitate a rapid acquisition of large datasets and a robust statistical analysis. Finally, a part of fundamental biological mechanisms, such as DNA repair investigated in this work, are highly conserved in eukaryotes. By comparing our experimental data of nuclear organization to simulated data, produced in parallel of this work, based on polymer physics, we have demonstrated that chromosomes self-organization is sufficient to reproduce the experimentally observed global organization. We then described die mobility of a subtelomere using a dedicated fluorescence microscopy system and new numerical analyzes. This mobility can be represented by 2 diffusion models at different lime intervals: short-tenu subdiffusion (typical in die case of a polymer) and long-term confinment (partly due to die crowded environment and chromosome anchoring). Finally, we studied the origin of the increased mobility of chromosomes after induction of DSB. We have also demonstrated the absence of modification of the chromatin's stiffness and compaction after DSB
Quête d'un cinéaste autour de la relation dialogique 'art-science' : de l'idée-sentiment dans le processus de création à une approche esthétique de la connaissance by Aurélien Peilloux( Book )

2 editions published in 2016 in French and held by 2 WorldCat member libraries worldwide

Cette thèse s'inscrit dans le domaine de la recherche-création, c'est-à-dire qu'elle allie une démarche de recherche universitaire et une pratique artistique : ici, la réalisation cinématographique. Ainsi, la production de ce travail se compose du traditionnel manuscrit, mais également de quatre films. Si leur statut est quelque peu dissymétrique, ils se renvoient l'un à l'autre, dialoguent, s'interpellent. Leur essence est commune': ils sont comme autant de tentatives de répondre à la problématique soulevée ici, à savoir l'invention d'objets hybrides 'art et science'. Cette problématique s'est développée dans deux directions. D'une part, la réalisation de films, où le concept scientifique devient une matière qui enrichit le langage cinématographique. D'autre part, une étude du processus créatif, à partir d'une méthodologie elle-même hybride, tentant d'articuler une approche scientifique et une approche personnelle, centrée sur mes propres expériences. Cependant, fondamentalement, ces deux approches s'opposent : la première repose sur une séparation entre le sujet pensant et l'objet de connaissance, tandis que la seconde se fonde sur une perception globale par le sujet réduisant à néant la distance entre lui et le monde. Mon expérience de cinéaste devait bientôt m'amener à privilégier la seconde approche, et à étudier le processus créatif à partir de mes propres expériences. De nouveau, l'aboutissement de cette réflexion est double : sur le plan scientifique, je propose une approche du processus créatif basée sur les propriétés de la forme esthétique. Sur le plan artistique, je réalisais deux films, interrogeant le cadre même de la pensée scientifique
Peut-on déléguer le tri des urgences ophtalmologiques à un algorithme informatisé auto-implémenté par le patient ? : le projet ICARE (Interactive Care Assessment of Risk factors and Emergency levels) by Mikaël Guedj( )

1 edition published in 2018 in French and held by 1 WorldCat member library worldwide

Every year in France, 4 million emergency consultations are not justified from a medical point of view and almost half of the patients presenting to the Emergency Department could be treated elsewhere, thus releasing the Emergency Departments to take care of the real urgent situations. The overcrowding of the ERs led the services to set up a prioritization of care for the reception of patients; this prioritization is not standardized nor rationalized. We designed a computerized tool to sort emergency levels based on a patient's symptoms, background, and medical context. By this tool, called iCare, the patient alone or assisted by a third party, must be able to detect and prioritize his symptoms leading to an urgent consultation, as opposed to less urgent or non-urgent symptoms. The evaluation of the iCare algorithm regarding ocular pathologies aims to run a generalizable and reproducible sorting tool within the different care units, but also to improve patient autonomy in the understanding of their symptoms and their use of the healthcare system (e-health concept of empowerment). The main objective of our "interventional research involving only minimal risks and constraints" was to validate the iCare sorting algorithm, determining the appropriate level of urgency corresponding to the clinical situations encountered. This validity was based on the calculations of sensitivity, specificity, positive and negative predictive values. The chosen gold-standard was the level of emergency determined by the doctor after his consultation. A number of 1000 patients presenting for an ophthalmological emergency were offered to participate in research upon arrival at the reception of two Parisian health centers (Rothschild Foundation, Vernes Institute), from the date of protocol acceptance by the Committee for the Protection of Persons in biomedical research (CPP). If the patient consented to participate in research, a Clinical Study Technician (CST) made him fill in the iCare algorithm, presented as an interactive questionnaire on touchscreen tablet, whose implementation took less than two minutes. At the end of this implementation, a level of emergency A, B, C or D was provided by the program. The level of emergency attributed by the algorithm was unknown to either the patient or the doctor who was going to examine him. The level of emergency determined by the physician at the end of his clinical examination (gold standard of the primary endpoint) was collected as a level A, B, C, D or as binary choice Urgent / No Urgent (U / NU). Other parameters, such as the time required and the need for filling assistance, the reason for consultation, demographics and on-site waiting time were also analyzed. This thesis outlines a state of the art of the word "e-health" in 2018, addresses the current public health issues related to high traffic in emergency services in France, and features the iCare tool as a potential solution to simplify and rationalize the sorting of emergency levels in ophthalmology (public health feature), as a means of health education and empowerment of patients in the reading of their symptoms (empowerment feature), but also as a generalizable tool for big data reporting of the reasons for consultation in the emergency wards, private practices or even at home health-related internet researches (epidemiological feature)
Development of the sense of ownership : social and moral evaluations by Belonia Gabalda( )

1 edition published in 2012 in English and held by 1 WorldCat member library worldwide

Since a very young age, the majority of human social interactions involve objects. In these interactions, children seem to take into account who owns what. The notion of ownership thus does not involve only a person and an object, but is a relationship between several persons with respect to an object. This relationship is organized by a set of rules or property rights. Our work deals with children's understanding of the notion of ownership. At what age do children acquire the understanding of property rights? Before an explicit mastery of the notion of ownership, do children have a more implicit understanding of it? More precisely, we explored the understanding and evaluation of illegitimate and legitimate transfers of property in children from 5 months to 5 years of age. We studied two types of ownership transgressions: illegitimate acquisition of an object (without owner's intention to transfer it), and absence of restitution of an object to its owner. In all our studies, we presented to children property transfers between two characters using non-verbal animated cartoons or movies with puppets as actors, and then measured children's understanding and evaluation of those transfers. The studies in Chapter 2 (Studies 1 and 2) assessed children's evaluation of different modes of acquisition of an object. The two experiments of Study 1 explored 3- and 5-year-olds's understanding and evaluation of illegitimate and legitimate property transfers. Adults were also tested as a control population. This study is the first one to investigate simultaneously children's explicit and implicit understanding of the notion of ownership, by asking questions about property rights, as well as social and moral evaluations of the characters implicated in the transfers, respectively. In Study 1a, participants saw a character acquiring an object either in an illegitimate way (theft condition) or in a legitimate one (gift-reception condition). In Study 1b, an illegitimate action (theft) was compared to a legitimate action (giving). 5-year-old children (as adults) showed both an implicit understanding of ownership through their social/moral evaluation (preferring the legitimate agent (gift recipient or giver) compared to the illegitimate agent (thief)), and an explicit understanding of ownership through their ability to attribute different property rights considering the legitimacy of the transfer. 3-year-old children did not make any distinction between the illegitimate and legitimate conditions in their evaluation, neither in their attribution of property rights. These results suggest that children acquire implicit and explicit understanding of ownership at the same time. In Study 1, no emotional reaction was present. We examined in Study 2 the role of the first possessor's emotions in 3-year-olds' evaluation of object acquisition. The same cue was present in the legitimate and illegitimate conditions: the first possessor being sad after both transfers. In the presence of this emotional cue, 3-year-olds managed to distinguish between the two conditions in their social/moral evaluation. This distinction could not have been based solely on the presence of a negative emotion, as the emotion displayed was the same in both conditions. We suggest that 3-year-old children detected the moral transgression in the theft condition, and used the negative emotion to confirm it. The studies in Chapter 3 (Studies 3 to 5) examined children's evaluations of the restitution of an object to its owner. Young children (2-3-year-old) have a bias to consider that the first possessor of an object is its “owner” and that the object cannot be definitively transferred to someone else. We thus investigated whether 3-year-old children (Studies 3 and 4) implicitly evaluate the absence of restitution as a transgression, and evaluate it negatively compared to the restitution of an object to its first possessor
Approches interdisciplinaires du domaine des vésicules extracellulaires : nouvelles méthodes et outils pour le transfert en clinique en médecine régénérative et délivrance de médicaments by Max Piffoux( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Les vésicules extracellulaires sont des nano-vésicules (100nm) comprenant les exosomes, microvesicules et corps apoptotiques, sécrétées par toutes les cellules de l'organisme. Elles ont des rôles physiologiques et physiopathologiques dans l'hémostase, l'inflammation, la transmission d'information et de molécules biologiques, les métastases, ou la régénération tissulaire. Par exemple, des vésicules issues de cellules souches mésenchymateuses ont le même effet que leur cellule mère dans la régénération du myocarde infarci, mais ont beaucoup d'avantages par rapport à ces dernières : possibilité de les conserver au congélateur, peu immunogènes, ne provoquant pas d'embolies, pas de risque de différentiation anarchique, etc. Toutefois, l'utilisation en clinique de ces vésicules reste difficile pour des raisons pratiques : très faible production par les cellules, difficulté à les caractériser, méthodes de chargement avec des agents thérapeutique peu reproductible, méthodes d'imagerie ou de d'ingénierie peu efficientes, etc. Nous avons développé des méthodes pour répondre à ces défis, croisant la biologie, la pharmacie et la physique, et avons pu découvrir que certaines de ces techniques pouvaient être utilisées dans d'autres domaines et pour d'autres indications. En pratique, pour répondre au problème de la caractérisation des vésicules, nous avons proposé une nouvelle méthode d'imagerie utilisant le microscope électronique en cellule liquide « in situ » pour observer des vésicules dans leur milieu liquide en temps réel, et peut être utilisé pour observer d'autres matériaux et phénomènes comme les liposomes ou des processus biologiques. Nous avons proposé une nouvelle méthode de chargement des vésicules avec des molécules thérapeutiques en les fusionnant avec des liposomes, permettant la délivrance d'agents de chimiothérapie plus efficacement que des liposomes. La méthode de production des vésicules à grand rendement a nécessité 3 d'itérations successives, toutes basées sur le même concept de vésiculation induite par une contrainte mécanique, et a abouti à une méthode efficace, scalable, et conformes aux standards de production pharmaceutique. La protéomique de ces vésicules montre des expressions de protéines plus proche d'un sous type de vésicule issues de la membrane plasmique appelées microvésicules. Les vésicules issues de cette méthode ont été testées in vitro avec succès, induisent un phénotype régénératif dans des modèles cicatrisation de fistule cutanéo-digestives et des modèles murins d'insuffisance cardiaque chronique. D'autres études sur les vésicules produites par cette méthode sont en cours sur la régénération osseuse, articulaire et cérébrale, ou la délivrance de médicaments et sur l'inhibition du phénomène métastatique en cancérologie. Nous commençons aujourd'hui à défricher le transfert de ces vésicules en clinique par le biais de productions en conditions pharmaceutiques dites et de la mise en place d'une start-up
Rôle des domaines de la Nétrine-1 sur l'organisation supramoléculaire et la mobilité de son récepteur DCC by Karen Uriot( )

1 edition published in 2015 in French and held by 1 WorldCat member library worldwide

Netrin-1 is a secreted cue involved in the development of the nervous system where it attracts neurons expressing the membrane receptor DCC and repulses those expressing UNC-5. Netrin-1 and DCC have also been implicated in colon tumorigenesis. Notably, Netrin-1 could directly act on the secreting cells and cause the gathering of DCC receptors. The formation of nanodomains of DCC would activate signaling cascades and prevent apoptosis. These nanodomains have been identified by crystallography of purified proteins but they have never been evaluated in cellulo. However, Netrin-1 can be recognized by a variety of receptors, like integrins for example, which could influence its ability to interact with DCC. In this work, we analyzed the interaction of Netrin-1 with DCC at the molecular level in living cells. To do so, deleted and mutated versions of Netrin-1 have been constructed and tested for their capacity to modify the membrane distribution and dynamic of DCC thanks to fluorescence microscopy. This study showed that Netrin-1 slows and confines DCC displacement in the plasma membrane where it would form nanodomains. Additionally, our techniques allowed highlighting the role of Netrin-1 N-glycosylations in its functionality as well as the involvement of its C-terminal domain witch would bind integrins through a RGD motif
Development of droplet-based microfluidic technology for high-throughput single-cell phenotypic screening of B cell repertoires by Raphaël Doineau( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

The adaptive immune system plays a leading role in defense against infection. The humoral response, involving the production of antibodies, is an important component of the adaptive immune response. During an infection, specific B cells of the immune system proliferate and release large amounts of antibodies which bind selectively to the target protein (antigen) found on the invading pathogen, inducing destruction of the pathogen. However, the immune system does not always respond efficiently enough to destroy pathogens, and tolerance mechanisms prevent the generation of antibodies against human protein - such as cell surface markers on cancer cells or cytokines involved in inflammatory and autoimmune disease - that could be important therapeutic targets. Hence, there is great interest in research and development of specific antibodies that can be used for immunotherapy of patients. Due to their high affinity and selective binding to antigens, monoclonal antibodies (mAbs) have emerged as powerful therapeutic agents. Monoclonal antibodies derived from single B cells have a unique sequence and display binding affinity for a specific antigen. However, until now, the discovery of mAbs has been limited by the lack of high-throughput methods for the direct and large-scale screening of non-immortalized primary B cells to uncover rare B cells which produce the specific antibodies of clinical interest. This is now becoming possible with the emergence and improvement of in vitro compartmentalization methods for single-cell encapsulation and screening in picoliter droplets. In my PhD project, I describe the development of binding immunoassays and microfluidic devices for the direct phenotypic screening of single-cells from enriched B cell populations. This development has enabled detailed analysis of the humoral immune response, with single-cell resolution and is an essential component of an antibody-discovery pipeline coupling single-cell phenotypic screening to single-cell antibody sequencing. It is now possible, for the first time, to screen millions of single B cells based on the binding activity of the secreted antibodies and to recover the antibody sequences
Au coeur du contrôle de l'immunité humorale : (re)définition, mode d'action et répertoire des lymphocytes T folliculaires régulateurs by Paul-Gydéon Ritvo( )

1 edition published in 2017 in French and held by 1 WorldCat member library worldwide

The immune humoral response offers the organism an efficient protection through the production of antibodies following an immune stimulation. Follicular regulatory T cell (Tfr) is an essential subset in the control of humoral immunity. These cells share with conventional regulatory T (Treg) cells regulatory functions and should play a major role in the control of antibody production following stimulation. As T follicular helper (Tfh) cells help is essential in the differentiation of B cell into antibody-producing plasma cells, one of the possible mechanisms of Tfr's control could be the limitation of the Tfh cells' help to the B cells. As a consequence of the non-response of Tfr cells to interleukin (IL)-2, we thoroughly revealed the CD25- phenotype of Tfr cells thus redefining the subset. This stringently-selected population allowed a fine-tuned characterization of Tfr cells and the discovery of an IL-1[beta] axis regulating the germinal center responses. The dual regulation of T cells in secondary lymphoid organs, one between Treg and Teff cells regulated by IL-2 outside germinal centers and the other between Tfh and Tfr cells regulated by IL-1 inside GCs brought us to question the origin and specificity of Tfr cells. We partially answered this with a high-resolution analysis of these populations' repertoires. We highlighted a similarity in the distributions and global characteristics of the follicular cells' repertoires regardless their regulatory (Tfr) or not (Tfh) phenotype. We also brought out the major sharing between Treg and Tfr repertoires underpinning the hypothesis of a common origin for these populations. This work has disclosed important aspects of Tfr cells' biology, a fundamental subset in the control of humoral immune responses. It opens many perspectives including the control of antibody production, negatively in the context of autoimmune diseases or its positive exploitation to enhance vaccine efficacy
Cardiac Arrest-Induced Brain Injury : Diagnostic And Prognostic Values of Circulating Biomarkers by Nicolas Deye( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Outcome of cardiac arrest (CA) remains dramatic. To quickly diagnose the cause of CA and establish a reliable outcome prediction (prognostication) as early as possible could help to guide initial treatments. It could avoid futile treatments in patients with low chance of survival or of good neurological recovery, or conversely allow treatment optimization in patients expected to have a high likelihood of good neurological outcome. Usefulness of biomarkers to guide clinicians in finding the CA diagnosis and helping prognostication is debated. Biomarkers are considered as not sensitive and accurate enough, especially within the first hours after return of spontaneous circulation (ROSC). Their use is only recommended in prognostication for Neuron Specific Enolase (NSE) as a second line tool and after the third day from CA. Our first study confirmed that biomarkers “specific” of brain injury (S100B protein: S100 and moreover NSE) cannot sufficiently discriminate the neurological cause of CA on ICU admission. If early coronary angiogram is the standard for diagnosing a probable cardiac cause of CA, biomarkers cannot replace brain computed-tomography (CT) in CA from a neurological cause. The second study evaluated, during the 1st day after ROSC, the link between biomarkers (S100 and NSE) and 2 surrogates of brain oedema recently proposed as outcome predictors: echography of the optic nerve sheath diameter (ONSD), and grey to white matter attenuation ratio (GWR) on brain CT-scan. Even though we cannot conclude on a definitive relationship between these parameters, ONSD enlargement at day 1 was associated with specific brain damage after CA, such as brain oedema and mostly axonal injuries, as reflected by increases in NSE (on admission and at day 1) and low GWR measurements. Whereas NSE, GWR and ONSD at day 1 were correlated, S100, which is more specific of glial injuries, did not reach significance. NSE and S100 on admission, at days 1 and 2 after ROSC, as well as ONSD at day 1, were associated with survival at hospital discharge. The third study evaluated the prognostic value of several biomarkers in the early phase after CA (NSE and S100 being sampled at median 220 min after ROSC). S100, blinded to physicians, was the biomarker with the best accuracy after ICU admission to correctly predict unfavourable outcome at hospital discharge and at 3 months after CA, compared with all other biomarkers such as lactate, pH, creatinine, and especially NSE. S100 variations during the first day after admission refined prognostication. Initial S100 was an early independent predictive factor associated with unfavourable outcome at hospital discharge, with the no-flow duration, initial lactate value, initial non-shockable rhythm, and the presence of clinical seizure. According to guidelines, prognostication theoretically needs to be delayed and multimodal, biomarkers alone not being recommended especially in the early phase after CA. Biomarkers cannot seem to be an alternative option compared to imaging to precisely diagnose the CA cause. By contrast, some biomarkers, such as S100 after admission, could easily and specifically discriminate CA patients with certainty of unfavourable outcome. Associated with other predictive tools (clinical or using imaging), biomarkers could interestingly be incorporated in early decisional algorithms to optimally guide initial therapies. This correct patient classification could help to avoid unuseful treatments versus to maximize aggressive therapies. The choice of recommended servo-controlled targeted temperature management devices, very efficient but invasive and expensive, or the indication -or not- of a cardio-circulatory assist device implementation should be guided in the early stage after ROSC using this simple strategy of patient selection
A nutritional epidemiology study of human gut microbiota - Associations with the systemic metabolism and usual diet of the host and relationships between dietary fibers and the host's health by Valentin Partula( )

1 edition published in 2019 in English and held by 1 WorldCat member library worldwide

Il est désormais admis que le microbiote intestinal joue un rôle prépondérant dans la santé de son hôte humain. Le co-métabolisme hôte-microbiote produit un très grand nombre de biomolécules intégrées au sein d'axes métaboliques complexes. De ce fait, le microbiote intestinal est considéré comme un organe endocrine à part entière. Bien que de nombreuses études se soient attachées à la caractérisation fonctionnelle spécifique de certaines molécules, les études envisageant plus globalement les relations métaboliques entre l'hôte et son microbiote intestinal restent rares. Parmi les nombreux facteurs influençant la composition et l'activité métabolique du microbiote intestinal, l'alimentation joue un rôle prépondérant. Toutefois, les relations entre l'alimentation usuelle et le microbiote intestinal n'ont pas été complètement élucidées. La compréhension des facteurs modulant le microbiote intestinal est un enjeu majeur des recherches actuelles, car des liens entre le microbiote intestinal et de nombreuses pathologies (troubles gastro-intestinaux, cardio-métaboliques, neuropsychiatriques, etc.) ont été suggérés. Dans ce contexte, nous avons utilisé une approche épidémiologique pour caractériser les associations entre la composition du microbiote intestinal d'une part et le métabolisme systémique et l'alimentation usuelle de l'hôte d'autre part, au sein de la population Milieu Intérieur (N=1 000). Enfin, dans la cohorte prospective NutriNet-Santé (N≈160 000), nous avons analysé les associations entre la consommation de fibres d'une part et le risque de maladies chroniques et le microbiote intestinal d'autre part.Nos résultats décrivent des associations spécifiques entre les caractéristiques du microbiote intestinal et certaines composantes du métabolisme de l'hôte, et suggèrent un rôle important de l'axe intestin-rein. De plus, des associations inverses entre la diversité du microbiote intestinal et la consommation d'aliments caractéristiques du régime occidental ont été détectées. Enfin, nos travaux confirment que la consommation de fibres est associée à une réduction du risque de maladies chroniques, dans un contexte où un nombre croissant d'études suggère une implication du microbiote intestinal dans de tels effets
Evolutionary genomics of conjugative elements and integrons by Jean Cury( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Beyond WEIRD : an interdisciplinary approach to language acquisition. by Camila Scaff( )

1 edition published in 2019 in English and held by 1 WorldCat member library worldwide

Jusqu'à présent, la majorité des recherches sur le développement des jeunes enfants provient de recherches centrées sur des populations dites « Occidentales, Eduquées, Industrialisées, Riches et Démocratiques (WEIRD en anglais ; Henrich, Heine, & Norenzayan, 2010). Il est moins documenté l'environnement de la petite enfance, les mécanismes d'apprentissage et les repères d'acquisition du langage des enfants qui grandissent dans des conditions autres que celles des « WEIRD ». J'ai contribué dans cette thèse à l'étude de l'impact de l'apport linguistique sur les résultats lexicaux en utilisant différentes approches méthodologiques ainsi que diverses populations. Ce document comporte : une méta-analyse explorant la relation entre le niveau socio-économique de l'enfant et le développement lexical précoce ; une étude empirique des effets du SE, du statut langagier et de l'âge sur le traitement lexical et le vocabulaire chez les jeunes enfants français ; et enfin, une étude utilisant des enregistrements pour analyser la quantité et les sources des apports linguistiques offerts aux enfants issus d'une communauté autochtone en Bolivie, les Tsimanes. Dans la discussion finale, je présente les avantages et les limites de la recherche interculturelle et les dangers de la généralisation à partir d'un seul type de contexte socio-écologique
Analyse haut-débit du comportement spontané d'un organisme modèle « simple » by Olivier Mirat( )

1 edition published in 2013 in French and held by 1 WorldCat member library worldwide

The use of simple genetic model organisms has allowed large-scale investigation of cellular and molecular mechanisms in biology. The zebrafish larva (Danio rerio) is a simple vertebrate model with several advantages for the identification of the molecular and pharmacological basis of development and behavior thanks to genetic and chemical screens. Several experimental paradigms rely on a precise behavioral characterization associated with a genotype or a drug application. This phenotyping process would benefit from a global comprehension of all possible zebrafish larvae maneuvers in order to precisely characterize the global behavior of larvae observed during an experiment. The analysis over multiple minutes of the spontaneous locomotion of zebrafish larvae in a group provides an ideal framework for achieving these goals.The manual analysis of animal behavior is possible for the observation of stereotyped and isolated maneuvers, but it is not compatible with large-scale approaches. After five days, the zebrafish larva moves in burst of movement occurring at high frequency and separated by a few seconds. The difficulty of observation of high-frequency maneuvers makes a manual analysis of videos impossible. The recent development of high-speed cameras, coupled with advances in computer science and artificial intelligence, make an automatic analysis of behavior possible. The available commercial solutions allow long acquisitions but without capturing all the complexity and diversity of the movements. We thus created ZebraZoom, our high-throughput analysis system which makes it possible to follow, quantify and categorize the spontaneous behavior of all zebrafish larva in a group.We built an experimental setup which consisted in placing seven 5- to 7-day old zebrafish larvae in eight petri dishes. The petri dishes were placed on a light table and a high-speed camera was placed above the setup and allowed to record the spontaneous behavior at 337 Hz during four minutes. Once the video was acquired, ZebraZoom localized automatically each of the eight petri dishes and followed the head and the tail of each of the animals on the entire video, thanks to computer vision methods. ZebraZoom then identifies automatically all burst of movement.The behavior phenotyping was performed thanks to two complementary methods: the extraction of global parameters characterizing movement dynamics and the automatic categorization of movements into stereotyped maneuvers. We used global parameters analysis to characterize the effect of drugs acting on neurotransmitters receptors and to analyze the behavior of a blind mutant. The automatic categorization of movements was carried out thanks to machine learning procedures. We showed the utility of this categorization method in studying interactions between larvae at early stages. In conclusion, our ZebraZoom program makes it possible to carry out an automatic and complete phenotyping, and this approach could be used in other systems and experimental contexts
The coevolution of gene mobility and sociality in bacteria by Tatiana Dimitriu( )

1 edition published in 2014 in English and held by 1 WorldCat member library worldwide

Les bactéries sont des organismes extrêmement sociaux, qui présentent de multiples comportements de coopération. De plus, les génomes bactériens sont caractérisés par la présence de nombreux éléments génétiques mobiles, tels que les plasmides. Ces éléments mobiles sont la cause de transferts génétiques horizontaux, et jouent un rôle important dans l'évolution bactérienne. La coopération et le transfert horizontal ont tous deux des conséquences importantes sur la santé humaine: des comportements coopératifs sont souvent à l'origine de propriétés de virulence chez les bactéries pathogènes, et le transfert horizontal entraîne la dissémination de gènes de résistance aux antibiotiques. L'évolution du transfert horizontal a jusqu'ici été analysée essentiellement en termes de bénéfices infectieux apportés à des éléments génétiques égoïstes. Cependant, le taux de transfert des plasmides est extrêmement variable et partiellement contrôlé par les gènes des bactéries hôtes, suggérant une co-évolution complexe entre hôtes et plasmides. De plus, les plasmides sont particulièrement riches en gènes liés à des comportements coopératifs, et semblent donc jouer un rôle-clé dans les phénomènes de socialité bactérienne. Ce travail porte sur la coévolution entre mobilité génétique et socialité chez les bactéries. Nous analysons ici les pressions de sélection agissant sur le transfert de plasmides et la production de biens publics, à l'aide de modèles mathématiques et d'un système synthétique que nous avons construit chez Escherichia coli, dans lequel nous pouvons contrôler indépendamment la coopération et la conjugaison. Dans un premier temps, nous montrons expérimentalement que le transfert horizontal favorise le maintien de la coopération dans une population structurée, en augmentant la sélection de parentèle agissant au niveau des gènes transférés. Dans un second temps, nous montrons expérimentalement et théoriquement que l'échange génétique lui-même peut être sélectionné: les bactéries transférant des plasmides codant pour des biens publics sont favorisées dans une population structurée. Le transfert de gènes codant pour des biens privés peut également être sélectionné, à condition que ce transfert s'effectue entre bactéries apparentées. Finalement, ces interactions entre transfert horizontal et coopération peuvent mener à une association entre allèles de coopération et de transfert, expliquant la fréquence élevée de gènes sociaux situés sur des plasmides.Ces résultats permettent de mieux comprendre le maintien de comportements coopératifs chez les bactéries, et suggèrent des moyens de cibler certains cas de virulence bactérienne
 
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École doctorale 474

École doctorale FDV

École doctorale FIRE

École doctorale Frontières du vivant

École doctorale Interdisciplinaire européenne frontières du vivant

ED 474

ED FDV

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ED Frontières de l'innovation en recherche et éducation

ED Frontières du vivant

ED Interdisciplinaire européenne frontières du vivant

ED474

FIRE

Frontières de l'innovation en recherche et éducation

Frontières du vivant

Interdisciplinaire européenne frontières du vivant

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