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Identification and Functional Characterization of an ABC Transporter of Haemonchus Contortus, the P-Glycoprotein 13 Marion A

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Identification and Functional Characterization of an ABC Transporter of Haemonchus Contortus, the P-Glycoprotein 13 Marion A Identification and functional characterization of an ABC transporter of Haemonchus contortus, the P-glycoprotein 13 Marion A. David To cite this version: Marion A. David. Identification and functional characterization of an ABC transporter of Haemonchus contortus, the P-glycoprotein 13. Toxicology. Université Paul Sabatier - Toulouse III, 2016. English. NNT : 2016TOU30206. tel-01665210 HAL Id: tel-01665210 https://tel.archives-ouvertes.fr/tel-01665210 Submitted on 15 Dec 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. TABLE OF CONTENTS 1 TABLE OF CONTENTS 2 TABLE OF CONTENTS Acknowledgements First, I would like to thank the various fundings that made this work possible: the Natural Sciences and Engineering Research Council of Canada, the FRQNT Centre for Host-Parasite Interactions, Quebec, and EMIDA ERA-NET project CARES n° 11-EMID-003-02. I also thank the Center for host- pathogens interactions (CHPI) that allowed me to extend my financial support for six months, the Université Paul Sabatier (UPS) in Toulouse, and the Frontenac Program of Quebec government that covered most of my travel fees between France and Canada. I would like to acknowledge Pr. Elias Georges, Dr. Jean-Michel Jault and Pr. Alexis Valentin for accepting to evaluate my PhD work. Many thanks go to my supervisors Dr. Anne Lespine and Dr. Roger K. Prichard for giving me the opportunity to do this PhD in co-direction between each of their laboratories in France and Canada. This was a very rewarding experience in many ways, both scientific and personal. Thanks for believing in me since the beginning and for always encouraging me to persist while Hco-Pgp-13 was giving us hard times to learn to know it. Thanks for all your advice and for watching over my work so that it followed the right track during all these years. Thanks for helping me with the extension of my PhD, thus allowing it to finish in the best possible conditions. I also would like to acknowledge my adivsory committee, Pr. Robin Beech and Dr. Cecile Menez, who gave much advice and helped many times with results analysis during the three years of my PhD. I would like to warmly thank the scientists who have highly contributed to the success of my PhD: Thanks to Dr. François André for welcoming me to its laboratory at the CEA and teaching me with bio/chemo-informatics. Thanks for teaching me patience and the art of perfectionism that work together. Thanks for the extensive help with results analysis, and for revising each part of the manuscripts as precisely as possible. Thanks to Dr. Stéphane Orlowski for the incredible amount of work on ABC transporter homologies studies. Thanks also for the help with writing and correcting articles. Thank you for all our scientific talks, about my thesis project or other subjects of interest, and for being someone as passionate about research as you are. I hope I learned everything I could from your philosophy of science. Thanks to Dr. Chantal Lebrun, for being a skilled biochemist with a passion for transmitting her knowledge. Thanks for having always been happy to help with experiments, to advice with strategies and troubleshooting, and to participate in my manuscript correction. Thanks for your contagious love of science and your great humanity. Thanks to the students who critically helped me during these 4 years. Thanks to Shaima Hashem for helping with my learning of in silico docking and homology modelling. Thanks for your availability and sense of humor. Thanks to Thomas Duguet for helping in many ways with immuno- fluorescence assays. Thanks for always being happy to collaborate and for being the best moaner in the Parasitology building after me, thus contributing to the French reputation. Thanks to Clément Frainay for his availability and the high amount of technical help provided for docking calculations run in Toulouse. Thanks for being a ninja of bioinformatics. 3 TABLE OF CONTENTS I also want to thank all other members of my both teams: in Montreal: Thanks to Kathy for teaching me most of techniques in McGill,and for various and extensive technical help during all my PhD, even from the other side of the ocean. Thanks to Hua for her precious advice with the nested PCR and for her sweetness. Thanks to Catherine for many scientific advice, long talks and valuable support. Thanks also to all the people who made this lab such a nice cosmopolitan place: Ludmel, Virginie, Aissatou, Nour, Pablo, Shoaib, Durai and Phillip. à ToxAlim, INRA : Merci à Jean-François, pour sa présence et pour tout le chocolat salvateur de mon estomac. Merci à Elise, pour « la tristitude » et sa joyeuse folie contagieuse. Merci à Léa, pour ne trouver aucune blague drôle mais pour avoir bien rit depuis son arrivée, et pour m’avoir aidé précieusement sur la dernière ligne droite ! Merci à Mélanie et Alice pour leur aide au tout début de ma thèse et à mon retour de Montréal. Enfin, merci aux étudiantes de licence pour avoir participé à mon projet avec joie : Christina, Elsa et Mélanie. A special thanks to the students I met in neighbor teams and who helped me in many ways: at the Institute of Parasitology, McGill: Adeline, thanks for coming back to the airport to take me back to your home on the 13th of November 2015, and for everything else. Krittika, so many thanks for running with me by -13°C, it was so “cool”! Thanks to all of the students of your team, for making me discover both Canadian and US American customs. Thanks to the Fauchers: Nilmini and Hana for making me travel to Sri Lanka and Tunisia just by talking with you. Finally, thanks to the best roommates ever: Sarah and Oscar, for being the kindest Quebecer and cat I could ever meet. à ToxAlim, INRA : Merci à Alix, Eli et Sarah d’avoir fait leur thèse la porte en face ou au bout du couloir, et d’avoir toujours été prêtes à s’entraider de diverses manières, et en particulier les derniers jours d’écriture, vous avez été géniales. Merci pour tous les précieux souvenirs accumulés pendant ces dernières années, j’espère que de nombreuses occasions d’en rajouter suivront. Merci à Isaura pour ton sourire permanent et les très bons moments partagés et merci aux étudiantes de l’équipe 05 qui y ont également participé. Merci à tous les autres, famille ou amis, loin de la science, qui m’ont soutenue de façon toute aussi importante : Au Canada: Merci à Marie-Jo et Dominik, Suzanne, Cynthia and Djé, pour être des exemples de sagesse, de force et de gaieté. Merci à Renata Heidersdorf pour ses merveilleux cours d’art qui m’ont aidé plus qu’il n’est imaginable dans mon projet scientifique. En France : Merci à mes parents pour avoir toujours accepté de me soutenir financièrement tout au long de ces quatre ans. Merci de m’avoir fait pousser à la campagne et d’avoir arrosé mes racines de votre amour pour les rendre plus solides que je n’aurais cru. Les fruits de mes années de travail sont aussi pour vous. Merci à ma grande famille, auprès de laquelle j’ai aimé me ressourcer. Merci aux précieux amis qui ont toujours été tout près quelquesoit la distance. Merci à Patty pour les trop rares moments partagés ces dernières années et à Léti pour n’avoir jamais hésité à m’accueillir à Paris dès qu’un séjour était nécessaire au CEA. Vous êtes les meilleures. Merci à Nicolas pour le soutien et les encouragements essentiels à ma fin de thèse, merci d’avoir été au bon endroit au bon moment ! Merci infiniment à Marie-Jo, pour les mots simples et percutants, qui reboostent en quelques phrases pour au moins des mois. Enfin, un immense merci à la Team AGL, qui s’agrandit toujours plus, merci à tous ces gens au grand cœur d’être entré dans ma vie ! Un merci spécial à Geneviève, sans qui l’aventure n’aurait jamais eu lieu, et qui veille comme une maman poule sur tous ses petits, et Valérie, inspirante de motivation et de bienveillance, une grande sœur inestimable. Enfin, merci à Ludo pour ton grand cœur fort si complémentaire à mon petit cœur sensible. 4 TABLE OF CONTENTS A Grégory Lemarchal, Pour m’avoir inspiré ma quête : « Tenter, sans force et sans armure D’atteindre l’inaccessible étoile […] Je ne sais si je serai ce héros Mais mon cœur serait tranquille » La Quête – Jacques Brel 5 TABLE OF CONTENTS 6 TABLE OF CONTENTS Table of contents TABLE OF CONTENTS ............................................................................................................ 1 LIST OF FIGURES AND TABLES OF THE LITERATURE REVIEW ............................... 5 ABBREVIATIONS ..................................................................................................................... 6 CONTRIBUTION OF AUTHORS ............................................................................................ 7 SCIENTIFIC VALORIZATION ................................................................................................ 8 GENERAL INTRODUCTION ................................................................................................... 9 LITERATURE REVIEW ................................................................................................. 15 I.
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