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Étude Biochimique Et Biophysique De L'arn Hélicase UPF1

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Étude Biochimique Et Biophysique De L'arn Hélicase UPF1 Étude biochimique et biophysique de l’ARN hélicase UPF1 : un moteur moléculaire hautement régulé Joanne Kanaan To cite this version: Joanne Kanaan. Étude biochimique et biophysique de l’ARN hélicase UPF1 : un moteur moléculaire hautement régulé. Biochimie, Biologie Moléculaire. Université Paris sciences et lettres, 2018. Français. NNT : 2018PSLEE008. tel-01878209 HAL Id: tel-01878209 https://tel.archives-ouvertes.fr/tel-01878209 Submitted on 20 Sep 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE DE DOCTORAT de l’Université de recherche Paris Sciences et Lettres PSL Research University Préparée à l’Ecole Normale Supérieure Étude biochimique et biophysique de l’ARN hélicase UPF1 : Un moteur moléculaire hautement régulé 515 Ecole doctorale n° COMPLEXITE DU VIVANT Spécialité BIOCHIMIE ET BIOLOGIE MOLECULAIRE COMPOSITION DU JURY M. TANNER Kyle Université Paris Diderot, Président du jury M. GRAILLE Marc Ecole Polytechnique, Rapporteur M. LEULLIOT Nicolas Paris Descartes, Rapporteur Mme. FROMONT-RACINE Micheline Soutenue par Joanne KANAAN Institut Pasteur, Examinatrice le 09 juillet 2018 h M. MARGEAT Emmanuel Université de Montpellier, Examinateur Dirigée par Hervé LE HIR M. LE HIR Hervé Ecole Normale Supérieure, Directeur de h thèse M. CROQUETTE Vincent Ecole Normale Supérieure, Membre invité Remerciements L’écriture de mon manuscrit de thèse fut un défi auquel je ne m’attendais pas. Après maintes soirées devant une page blanche, je me rends compte que la plus grande difficulté que j’ai eue repose dans tout ce que ce document symbolise : la fin d’une aventure inoubliable. Et de toutes les phrases que j’ai dû écrire pendant ma thèse, les plus dures à mettre noir sur blanc sont dans ce paragraphe de remerciements. Comment pourrai-je remercier toutes les personnes sans qui cette aventure n’aurait vu ni le jour, ni la fin ? Je commencerai d’abord par les membres du jury, qui seront les premiers à lire ces mots. Madame Micheline Fromont-Racine, et Messieurs Emmanuel Margeat, Kyle Tanner et Vincent Croquette, je vous remercie de votre temps et votre contribution à l’évaluation de mon travail. Messieurs Marc Graille et Nicolas Leulliot, merci de votre travail minutieux et de votre contribution à ce manuscrit, mais surtout de m’avoir considérée digne de soutenir ma thèse et partager mon travail. Je tiens aussi à remercier le Memolife Labex, la fondation ARC pour la recherche contre le cancer et l’agence nationale de la recherche (ANR), dont les financements ont rendu ce travail possible. A l’équipe HLH, ma deuxième famille. Bientôt cinq ans que l’on se connait. Vous m’avez vue dans tous mes états ; vous m’avez accompagné tous les jours, vous m’avez vu rigoler, pleurer, vous m’avez consolé et conseillé. Nous avons fêté ensemble mes 23, 24, 25 et 26 ans, ma naturalisation, mes fiançailles, … bref ; merci pour chacun de vos gentils mots, merci pour vos encouragements, merci de m’avoir accueillie parmi vous. Je suis fière de faire partie du clan des HLH. Au porteur des initiales de ce clan, Hervé, tant de choses pour lesquelles je voudrais te remercier. Pour commencer, merci d’avoir accepté, un beau jour d’octobre 2013, d’accorder un peu de temps à la petite libanaise qui venait d’arriver à l’IBENS et qui cherchait un stage de master. Dès ce jour, elle avait trouvé son labo de thèse où elle allait passer une belle aventure. Grâce à toi, cette petite libanaise a grandi non seulement en tant que chercheuse, mais aussi en tant qu’être humain. Merci de la confiance que tu m’as accordée, d’avoir écouté mes idées les plus farfelues, même quand elles consistaient à jouer au lego avec des protéines pour faire des chimères ; merci de m’avoir poussé quand il le fallait aux moments clés : « Joanne, quand tu reviens de vacances, tu te mets aux manips de molécule unique ! ». Merci pour les Rocky Mountains (on a vu un moose!), la Grèce, Toulouse, l’Allemagne, l’Espagne, où j’ai pu apprendre et partager la science. Fra, la première italienne du labo. Sans toi ce projet n’aurait jamais vu le jour. Tu es aussi processive qu’UPF1, ta passion pour la science et ta patience sont une source d’inspiration. Je te remercie pour tes conseils, ton encadrement, nos échanges professionnels et personnels, et ta bonne humeur infaillible. La prochaine fois qu’on se revoit, ce sera avec un gâteau Marks and Spencer qui pèse 30 kilos et qui aura fait le voyage Paris-Lyon en train ! Isa, alias Capitaine Barbosa, la Reine des Western, ou aussi la mémoire du labo. Toujours un sourire aux lèvres, un gentil mot à dire, un conseil à donner, une phrase pour consoler, et des M&Ms dans les poches pour les moments de crise. Merci pour ton amitié, ton support continu et ta bonté de cœur. Nos conversations entre deux poteaux accompagnées de torticolis vont me manquer. Virgi, la deuxième Italienne du labo, et ma coloc de bureau. Tes « Holà Chica », tes « Bellissima », «Bravissima » et tes éternuements incroyablement bruyants vont me manquer. Sans toi, le labo aurait été trop calme. Merci pour ta spontanéité, tes encouragements, ton support et ton amitié. Quentin (alias LALA), Toni (alias Janio) et Olivier (alias OB), ce fut un plaisir de travailler à vos côtés. Toujours souriants, vous rendez la vie au labo agréable et joyeuse. Je vous remercie pour vos encouragements, vos conseils, et nos discussions de midi. Oh Sung, it was pleasure to get to know you and work with you. Your good humor and smiles have added a joyful spirit to the lab. Thank you for your kindness and all the gifts you have brought us. Je tiens à remercier tous les anciens membres de l’équipe et les stagiaires avec qui j’ai eu l’occasion de travailler et de partager de bons moments : Rémi, Rahul, Raphael, Zhen, Jérôme, Laetitia, Arthur, Mathias et Irène. Je remercie en particulier Emélie et Leila, mes deux « grandes sœurs ». Merci d’avoir toujours été prêtes à m’écouter, me conseiller, me consoler, et partager mes joies et mes tristesses. A l’équipe ABCD. Au bout de trois ans de va-et-vient entre l’IBENS et le département de physique, je pense pouvoir postuler au moins officieusement au titre de membre de votre équipe (A temps partiel). Merci de m’avoir accueillie parmi vous et de m’avoir expliqué (et réexpliqué, et réexpliqué…) tous les concepts de physique dont j’ai eu besoin pendant ma thèse. Je tiens notamment à remercier Vincent, pour sa patience, sa gentillesse, son ingéniosité, ses explications, et sa métaphore de cuisson des patates pour me faire comprendre une fois pour toute son modèle mécanistique. Saurabh, you have been not only a great colleague to work with, but an amazing friend that I am so grateful I met. My whole thesis would have not been the same without you. I will always cherish the long hours we have spent in front of the magnetic tweezers, waiting to see what surprises UPF1 was holding for us. Thank you for your support, your trust, your advices, and your kindness. The work of this thesis is the product of our combined efforts but most importantly of our friendship. Au sein de la section GF et de l’IBENS, je voudrais remercier tous les collègues que j’ai connus et croisés, qui rendent la vie agréable au travail. Je remercie aussi Brigitte et Abdul, toujours prêts à nous aider pour nos tâches administratives. Martine, merci pour tout ton travail, sans toi je n’aurai jamais pu effectuer plus de 80 purifications de protéines grâce à tout le matériel que tu nous prépares. Je te remercie aussi pour ta bienveillance et tes conseils. Je clôture mes remerciements au sein de l’ENS par deux personnes. Amhed, tu as été mon tout premier ami à l’IBENS et en France. De toute ma vie, je n’ai jamais connu une personne aussi gentille, généreuse, compatissante et galante. Merci pour ton support continu, ton écoute, ta joie de vivre, ta bonté et ton amitié. Patrick, mon compatriote aux idées out of this world. 10 ans maintenant que tu es parti de notre motherland, mais tu gardes toujours en toi la générosité et la chaleur du peuple libanais. Toujours prêt à faire la fête, mais aussi à travailler dur pour réussir tous tes projets (très très nombreux). Je te remercie pour ta confiance en moi et tes encouragements continus, mais surtout d’avoir accepté la mission impossible consistant à me rappeler que ce n’est pas la fin du monde de se détendre parfois et profiter de la vie. En dehors de l’ENS, je tiens à remercier ma famille et mes amis en France : Christine et Najah, les Tchous et leurs deux petits bouts de chou (Hélène et Benjamin), Martine et Etienne, Nathalie, Joe et Jade, Toni, et Rita. Guy, ce manuscrit est à toi. Sans ton support infaillible et ton attention, je n’aurais pas pu surmonter les difficultés quotidiennes. Merci pour ta présence continue à mes côtés, ta bonté, ta générosité, et ton amour. J’espère que toutes les aventures qui nous attendent seront encore meilleures que celles que nous avons vécues ces dernières années.
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