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Diversité Des Modes De Résistance De Cible Aux Antivitamines K Chez Les Rongeurs Joffrey Goulois

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Diversité Des Modes De Résistance De Cible Aux Antivitamines K Chez Les Rongeurs Joffrey Goulois Diversité des modes de résistance de cible aux antivitamines K chez les rongeurs Joffrey Goulois To cite this version: Joffrey Goulois. Diversité des modes de résistance de cible aux antivitamines K chez lesrongeurs. Biochimie [q-bio.BM]. Université de Lyon, 2016. Français. NNT : 2016LYSE1048. tel-01504208 HAL Id: tel-01504208 https://tel.archives-ouvertes.fr/tel-01504208 Submitted on 9 Apr 2017 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. N°d’ordre NNT : 2016LYSE048 THESE de DOCTORAT DE L’UNIVERSITE DE LYON opérée au sein de l’Université Claude Bernard Lyon 1 Ecole Doctorale « EDISS » ED 205 (Ecole Doctorale Interdisciplinaire Science-Santé) Spécialité de doctorat : BIOCHIMIE Soutenue publiquement 08/04/2016, par : Joffrey GOULOIS DIVERSITÉ DES MODES DE RESISTANCE DE CIBLE AUX ANTIVITAMINES K CHEZ LES RONGEURS Devant le jury composé de : Payen GAY, Léa Maître de Conférences Toxicologie Université Lyon 1 Présidente Gouat, Patrick Maître de Conférences Université Paris 13, LEEC Rapporteur Petit, Claude Professeur de Pharmacie-Toxicologie ENVT Rapporteur Michelin, Yves Professeur Campus agronomique de Clermont Rapporteur Esther, Alexandra Chercheur Julius Kühn-Institut Examinatrice Brouat, Carine Chargée de Recherche CBGP Montpellier SupAgro Examinatrice Benoit, Étienne Professeur Biochimie et Endocrinologie VetAgro-Sup Directeur de thèse Lattard, Virginie Maître de Conférences Pharmacie VetAgro-Sup Co-directrice de thèse Caruel, Hervé Responsable centre R&D Liphatech Invité UNIVERSITE CLAUDE BERNARD - LYON 1 Président de l’Université M. François-Noël GILLY Vice-président du Conseil d’Administration M. le Professeur Hamda BEN HADID Vice-président du Conseil des Etudes et de la Vie Universitaire M. le Professeur Philippe LALLE Vice-président du Conseil Scientifique M. le Professeur Germain GILLET Directeur Général des Services M. Alain HELLEU COMPOSANTES SANTE Faculté de Médecine Lyon Est – Claude Bernard Directeur : M. le Professeur J. ETIENNE Faculté de Médecine et de Maïeutique Lyon Sud – Charles Directeur : Mme la Professeure C. BURILLON Mérieux Directeur : M. le Professeur D. BOURGEOIS Faculté d’Odontologie Directeur : Mme la Professeure C. VINCIGUERRA Institut des Sciences Pharmaceutiques et Biologiques Directeur : M. le Professeur Y. MATILLON Institut des Sciences et Techniques de la Réadaptation Directeur : Mme. la Professeure A-M. SCHOTT Département de formation et Centre de Recherche en Biologie Humaine COMPOSANTES ET DEPARTEMENTS DE SCIENCES ET TECHNOLOGIE Faculté des Sciences et Technologies Directeur : M. F. DE MARCHI Département Biologie Directeur : M. le Professeur F. FLEURY Département Chimie Biochimie Directeur : Mme Caroline FELIX Département GEP Directeur : M. Hassan HAMMOURI Département Informatique Directeur : M. le Professeur S. AKKOUCHE Département Mathématiques Directeur : M. le Professeur Georges TOMANOV Département Mécanique Directeur : M. le Professeur H. BEN HADID Département Physique Directeur : M. Jean-Claude PLENET UFR Sciences et Techniques des Activités Physiques et Sportives Directeur : M. Y.VANPOULLE Observatoire des Sciences de l’Univers de Lyon Directeur : M. B. GUIDERDONI Polytech Lyon Directeur : M. P. FOURNIER Ecole Supérieure de Chimie Physique Electronique Directeur : M. G. PIGNAULT Institut Universitaire de Technologie de Lyon 1 Directeur : M. le Professeur C. VITON Ecole Supérieure du Professorat et de l’Education Directeur : M. le Professeur A. MOUGNIOTTE Institut de Science Financière et d'Assurances Directeur : M. N. LEBOISNE 2 Mémoire de Thèse - J. GOULOIS Remerciements Le travail de synthèse que nécessite la rédaction d’une thèse n’est pas évident, mais cette page de remerciements est sans aucun doute celle qui aura nécessité le plus d’efforts et d’attention de ma part, tant je tiens à remercier comme il se doit toutes les personnes ayant contribué directement ou non à ce travail. Mes premiers remerciements vont à chacun des membres de mon jury. Je remercie très sincèrement M. Claude Petit, M. Patrick Gouat et M. Yves Michelin d’avoir accepté de rapporter cette thèse. Merci pour le temps que vous avez consacré à la lecture de mon manuscrit ainsi qu’à l’élaboration de votre rapport, pour vos suggestions et vos remarques judicieuses. Je remercie chaleureusement Mme. Alexandra Esther, Mme Carine Brouat et M. Hervé Caruel d’avoir accepté d’être membre de mon jury de thèse. Je suis également très reconnaissant et honoré que Mme. Léa Payen Gay ait accepté de présider ma soutenance de thèse. J’adresse également toute ma gratitude à Liphatech et à chacune des personnes travaillant au sein de cette entreprise. Je tiens particulièrement à remercier Hervé Caruel, Lionel Legros et Florian Peigneau. Hervé, je te remercie d’avoir été mon encadrant au sein de la société durant ces 3 années, et d’avoir toujours été disponible pour moi. Florian, merci pour ton aide précieuse avec les souris. Attraper une souris sauvage n’est vraiment pas évident, je défie quiconque de le faire avec autant d’aisance que toi. En revanche, je t’avoue que nos petits voyages à la benne d'équarrissage d'animaux ne vont pas me manquer ^^. Lionel, j’ai vraiment pris grand plaisir à travailler avec toi. Tu m’as montré une vision du monde professionnel me permettant de faire la passerelle entre le monde du laboratoire et la réalité du terrain et du marché. De plus, je te suis vraiment reconnaissant pour les congrès que nous avons faits ensemble, toutes ces expériences ont largement contribué à me faire murir. Je te remercie sincèrement. Je tiens à remercier spécialement mes deux encadrants de thèse, à savoir Etienne Benoit et Virginie Lattard. Sur le cadre scientifique, vos connaissances et votre capacité à jongler avec toutes vos responsabilités sont impressionnantes. Je vous suis vraiment reconnaissant d’avoir assuré un encadrement aussi rigoureux tout au long de ces années. Malgré vos nombreuses occupations vous avez toujours su vous rendre disponibles pour répondre à mes 3 Mémoire de Thèse - J. GOULOIS interrogations, et pour suivre chacune des étapes de cette thèse. D’un point de vue humain maintenant, l’un comme l’autre, vous êtes justes exceptionnels. Je connais très peu de personnes qui prennent autant soin de leurs employés. Vous vous donnez à fond pour que le laboratoire tourne bien et pour que chaque personne s’y sente bien. Etienne, j’ai mis pas mal de temps pour quitter le vouvoiement… je te remercie : d’avoir passé autant de temps pour passer tous mes échantillons à la MS, de m’avoir permis de « squatter » ton bureau durant tout le temps de la rédaction, de tes précieux conseils et pour ta générosité constante. Virginie, tu m’as suivi durant ces 3 années, toujours présente pour quoique ce soi. Merci de m’avoir fait confiance pour cette thèse. Je garderais aussi de sacrés bons souvenirs de nos entrainements au jujitsu sur le tatami ^^. Pour tout cela, vous avez ma profonde gratitude et mon respect. Je tiens aussi à remercier Philippe Berny qui m’a permis d’entrer au sein de l’école vétérinaire en m’acceptant en stage de master 2. Tu m’as introduit dans la problématique des rongeurs sauvages qui m’a de suite intéressée et j’ai eu la possibilité de poursuivre en thèse. Cette thèse a été le fruit du travail de plusieurs personnes, pas seulement le mien. J’ai eu la chance d’encadrer plusieurs stagiaires, qui de par leur travail, ont apporté plus qu’une pierre à l’édifice. Je dis bien une CHANCE, car c’est vraiment une partie de la thèse que j’ai le plus appréciée. C’est un exercice difficile d’encadrer un stagiaire, dans lequel j’étais novice, mais ce fut vraiment enrichissant. Ainsi, je remercie Joachim Mornet, Claire Hascoet, Audrey Chapuzet et Anne Sophie Pingon. Vous avoir encadré a été un plaisir. Je tiens aussi à remercier chaleureusement Abdessalem Hammed et Benjamin Matagrin, qui ont pris le temps de me former sur chacune des manips, m’ont transmis leur expérience et leur rigueur scientifique. Vos conseils ont été précieux. Un immense remerciement à tous les collègues : Marlene Damin-Pernik, Arnaud Michaux, Khedidja Dorani, Claire Hascoët, Ludivine Giraud, Sebastien Lefebvre, Maylis Boitet, Edwige Rousseliére, Solange Couturier, Damien Guyomar. Nous avons su allier travail et plaisir, et vous êtes devenus bien plus que des collègues à mes yeux. Sans aucun doute, vous allez me manquer. De nombreux stagiaires sont également passés au labo durant ces 3 années : BTS, IUT, Master, stagiaires véto, ils ont amené leur bonne humeur. 4 Mémoire de Thèse - J. GOULOIS J’ai une pensée particulière pour une certaine demoiselle nommée Selena Farez, je te remercie d’avoir pris le temps de relire mon manuscrit, pour tes conseils judicieux, pour toutes les monstrueuses fautes d’orthographe corrigées. Marlene, merci aussi pour avoir participé à la relecture. Tu seras la prochaine à soutenir, mais avant cela, de merveilleux moments t’attendent, je penserai bien à toi. Je ne peux terminer ces remerciements sans remercier mes amis, mes proches, pour leur soutien et simplement, leur amitié. Je suis pudique de nature, je ne sais pas vraiment faire des compliments et vous le savez bien, je préfère vous taquiner, mais je tiens beaucoup à vous. Vous d’Arras, de Lens, de Grenoble, de Lyon et du Brésil. Sur Lyon, durant ces 3 années j’ai eu la chance de rencontrer et de me lier avec plusieurs personnes qui se reconnaîtront. Je n’ai aucun regret, que de bons souvenirs. Je nommerai tout de même mon amie d’enfance, Elise Couteux, ma paupiette d’amour.
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