La cellule est l’élément fondamental de la vie. Plus d’une vingtaine de trillions de cellules forment les organes et tissus de notre corps. Ces cellules sont de taille spécifique puisqu’elles ont des fonctions précises au sein de leur tissu respectif. Dans la plupart des cas, les cellules doivent proliférer en se divisant pour se renouveler et ainsi assurer le bon fonctionnement d’un organisme. La dernière étape de la division cellulaire, la cytokinèse, est exécutée par la contraction d’un anneau contractile d’actomyosine, nécessaire pour effectuer la séparation physique de la cellule en deux cellules filles. La première partie des travaux décrits dans cet ouvrage portent sur la caractérisation de la cytokinèse en utilisant, comme modèle in vivo, les cellules précurseur de la vulve (VPCs) du nématode C. elegans. Notre étude révèle que plusieurs aspects de l’anneau d’actomyosine s’ajustent en fonction de la taille de la cellule. Entre autres, la largeur de l’anneau contractile, juste avant sa constriction, s’ajuste en fonction de la longueur des VPCs. De plus, la rapidité avec laquelle l’anneau se contracte dépend de la circonférence de la cellule. Ces découvertes nous ont amené à nous demander comment la cellule régule sa taille? Les cellules en prolifération maintiennent leur taille en homéostasie en équilibrant leur taux de croissance et de division cellulaire. Afin d’interroger les gènes impliqués dans le maintien de la taille cellulaire du mammifère, nous avons utilisé la technologie CRISPR/Cas9, afin d’éliminer par délétion tous les gènes humains, à raison d’un par cellule, pour identifier ceux qui causent une augmentation ou une diminution de la taille cellulaire. Cette étude nous a permis d’identifier plusieurs gènes déjà connus régulant la croissance cellulaire. De plus, nous avons identifié un groupe de gènes, incluant TLE4 un corépresseur de la transcription que nous avons caractérisé, n’ayant jamais été associé avec une fonction de contrôle de la taille cellulaire chez les mammifères. En somme, nos travaux ont contribué à l’approfondissement des connaissances sur la division cellulaire, plus précisément la cytokinèse, et des gènes impliqués dans le maintien de la taille cellulaire. Une meilleure connaissance du fonctionnement de ces deux évènements cellulaires est essentielle puisque leur dérégulation peut entrainer plusieurs pathologies, incluant le cancer. / Cells are the fundamental building blocks of life. The human body contains over twenty trillion cells that make up the different tissues and organs of our bodies. Cells within organs are of specific sizes to perform their specialized functions. In most cases, these cells must divide to proliferate and replenish the population of cells essential for proper organism function. The final stage of cellular division, termed cytokinesis, entails the assembly and constriction of a contractile ring that drives the dramatic cell shape changes required to physically partition the cell into two daughter cells. The first part of the work presented in this thesis addresses the characterization of cytokinesis in the epithelial vulval precursor cells (VPCs) of the nematode worm C. elegans. This study principally revealed that several aspects of cytokinesis scale with cell size. For instance, I observed that the breadth of the actomyosin ring scaled with VPC length. In addition, the speed of contractile ring constriction scaled with the circumference of VPCs. These scaling events raised the more general question as to how cells regulate their size. Proliferating cells attain cell size homeostasis by balancing cell growth and cell division. In order to define the molecular regulators of size in human cells a genome-wide approach was taken. Recently developed CRISPR/Cas9 technology was used to perform the first pooled knockout screens for human cell size regulators in the NALM-6 pre-B lymphocytic cell line. These screens revealed many genes that affect the size of NALM-6 cells, a number of which were previously known to be involved in growth regulation. In addition, these screens revealed the identity of many genes with no previously established functions associated with cell size regulation. Amongst the previously unknown regulators, I characterized the function of a co-repressor of transcription, TLE4, which I showed functions as a regulator of the B-cell lineage. This work contributes to the knowledge of the mechanics of cytokinesis in C. elegans epithelial cells and of the genes that coordinate cell size in humans. These results provide insights into cell growth and division in normal cells and how these processes may be perturbed in cancer and other diseases.

Made available in DSpace on 2015-03-05T18:11:57Z (GMT). No. of bitstreams: 0 Previous issue date: 23 / Nenhuma / As Verb-Particle Constructions (VPCs) são construções verbais características da língua inglesa constituídas por um verbo e uma ou duas partículas. Tais estruturas são sintática e semanticamente complexas, uma vez que não se enquadram em regras lógicas e homogêneas. Esta pesquisa visa fazer uma reflexão sobre a semântica das partículas nas VPCs apoiada em conceitos teóricos da Gramática Cognitiva e da Lingüística Cognitiva. A contribuição semântica das partículas away, out e over é discutida valendo-se de esquemas imagéticos que permitem fazer relações entre os diferentes significados das partículas encontrados nas VPCs selecionadas para a análise. Através das ferramentas da Lingüística de Corpus, mais especificamente um concordanciador gratuito chamado AntConc 3.2.1w, foram selecionadas para a análise as cinco VPCs mais freqüentes do American National Corpus com cada partícula. Como resultado, percebeu-se que as partículas contribuem em diferentes graus para o significado total das VPCs, podendo apresentar s / Verb-Particle Constructions (VPCs) are verbal constructions typical of the English language formed by a verb and one or two particles. Such structures are syntactically and semantically complex due to the fact that they do not fit into logical and homogeneous rules. This research aims at examining the semantics of particles in VPCs within the framework of Cognitive Grammar and Cognitive Linguistics. The discussion of the semantic contribution of the particles away, out and ‘over’ is grounded in image schemas which allow establishing relations among the different meanings of particles found in the VPCs selected for the analysis. By using Corpus Linguistics tools, namely a concordancer called AntConc 3.2.1w, the five most frequent VPCs with each particle in the American National Corpus were selected for the analysis. The results showed that the particles contribute to the overall meaning of VPCs in different degrees, with more and less metaphorical senses