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Study of the Pair Netrin-1/DCC in Parkinson's Diseas

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Study of the Pair Netrin-1/DCC in Parkinson's Diseas Study of the pair Netrin-1/DCC in Parkinson’s diseas Marie Jasmin To cite this version: Marie Jasmin. Study of the pair Netrin-1/DCC in Parkinson’s diseas. Cellular Biology. Université de Lyon, 2018. English. NNT : 2018LYSE1320. tel-02319442 HAL Id: tel-02319442 https://tel.archives-ouvertes.fr/tel-02319442 Submitted on 18 Oct 2019 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 : 2018LYSE1320 THESE de DOCTORAT DE L’UNIVERSITE DE LYON opérée au sein de l’Université Claude Bernard Lyon 1 Ecole Doctorale N° 340 Biologie Moléculaire Intégrative et Cellulaire Spécialité de doctorat : Discipline : Biologie cellulaire et intégrative Soutenue publiquement le 12/12/2018, par : Marie Mélissa Jasmin Etude de Netrin-1 et de son récepteur DCC en tant que nouvelles pistes thérapeutiques contre la maladie de Parkinson Devant le jury composé de : ARRIGO André-Patrick, Professeur Emérite, UCBL1 Examinateur MANN Fanny, DR, Université Aix Marseille, Rapporteure MOYSE Emmanuel, Professeur, Université de Tours Rapporteur MEHLEN Patrick, DR, CRCL Examinateur SAARMA Mart, Professeur, Institut de Biotechnologie de Helsinki Examinateur SAUDOU Frédéric, PU-PH, Grenoble Institut des Neurosciences Examinateur VOUTILAINEN Merja, Professeure auxiliaire, Institut de Biotechnologie de Helsinki Examinatrice FOMBONNE Joanna, MCU UCBL1, CRCL Directrice de thèse Acknowledgements / Remerciements UNIVERSITE CLAUDE BERNARD - LYON 1 Président de l’Université M. le Professeur Frédéric FLEURY Président du Conseil Académique M. le Professeur Hamda BEN HADID Vice-président du Conseil d’Administration M. le Professeur Didier REVEL Vice-président du Conseil Formation et Vie Universitaire M. le Professeur Philippe CHEVALIER Vice-président de la Commission Recherche M. Fabrice VALLÉE 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 Mérieux Directeur : Mme la Professeure C. BURILLON Faculté d’Odontologie Directeur : M. le Professeur D. BOURGEOIS Institut des Sciences Pharmaceutiques et Biologiques Directeur : Mme la Professeure C. VINCIGUERRA Institut des Sciences et Techniques de la Réadaptation Directeur : M. le Professeur Y. MATILLON Département de formation et Centre de Recherche en Biologie Humaine Directeur : Mme la Professeure A-M. SCHOTT COMPOSANTES ET DEPARTEMENTS DE SCIENCES ET TECHNOLOGIE Faculté des Sciences et Technologies Directeur : M. F. DE MARCHI Département Biologie Directeur : M. le Professeur F. THEVENARD Département Chimie Biochimie Directeur : Mme C. FELIX Département GEP Directeur : M. Hassan HAMMOURI Département Informatique Directeur : M. le Professeur S. AKKOUCHE Département Mathématiques Directeur : M. le Professeur G. TOMANOV Département Mécanique Directeur : M. le Professeur H. BEN HADID Département Physique Directeur : M. le Professeur J-C 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. le Professeur E.PERRIN 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 Acknowledgements / Remerciements ACKNOWLEDGEMENTS / REMERCIEMENTS This dissertation entitled " Etude de Netrin-1 et de son récepteur DCC en tant que nouvelles pistes thérapeutiques contre la maladie de Parkinson/ Study of the pair Netrin-1/DCC in Parkinson’s disease " is based on an article in preparation, fruit of a collaborative work between the laboratories of Dr. Patrick Mehlen, Prof. Mart Saarma and Dr. Keqiang Ye, which I sign as 1st author. The dissertation is written in English and will be presented publicly on December 12, 2018 to obtain the title of Doctor. I would like to thank the members of the jury, Dr. Fanny Mann, Dr. Merja Voutilainen, Prof. Emmanuel Moyse, Prof. Frédéric Saudou, Prof. Mart Saarma and Prof. Patrick Arrigo, for accepting to evaluate this work. Thanks also to the reviewers of the thesis for the time spent reading and evaluating the dissertation (despite the shortened deadline). I want to thank the Michael J Fox Foundation (MJFF) and the France Parkinson Association for supporting the research project presented in this thesis, with a grant and a fellowship respectively. This dissertation also represents the culmination of four years of an exciting adventure that was my thesis work (and life). Indeed, I call it an "adventure", because this project was challenging from the beginning since I had to set up new tools and to initiate a new research topic in my host laboratory. However, this experience was "exciting" because it taught me a lot about a fascinating organ and an intriguing topic, respectively the brain and neurodegenerative diseases. Furthermore, it also taught me a lot about the numerous features of a researcher (asking quotations, making orders, drafting of patent, writing applications for project authorization, for grants or scholarships, etc.). All this would not have been so motivating and productive without the support of my PhD supervisor, Dr. Joanna Fombonne, and the big boss, Dr. Patrick Mehlen, without the help of colleagues and collaborators, and the encouragement and love of my friends and my family. To all of them, I would like to express my deepest gratitude. Indeed, I thank Patrick Mehlen for trusting me and giving me the opportunity to develop this research project, relatively independently, in his laboratory. Thank you, Patrick, for believing in me from the very first day and for giving me the opportunity to go and train in Helsinki in the laboratory of Mart Saarma. Thank you for your support and your continual optimism. Thank you, Joanna, for your trust and for guiding me and helping me when I needed it. Your guidance was always valuable and motivating. I really enjoy the trio we make with Cathy. Thank you to both of you for being alternatively my brain and my hands…I know I can count on you. I warmly thank Prof. Mart Saarma and Dr. Merja Voutilainen for their valuable advice and for this great collaboration. Your expertise and deep understanding on science has been most impressive and inspiring. I am particularly grateful to Prof. Saarma for having welcomed me for 3 Acknowledgements / Remerciements several months in his outstanding laboratory at the Institute of Biotechnology of Helsinki, and I also want to thank the members of his team and excellent collaborators for their warm welcome and their help, in particular Mikko Airavaara, Katrina Albert, Andrii Domanskyi, Polina Stepanova. Merja, thank you for your kindness and for our continuous exchanges through which I learned a lot. I also thank the members of my thesis committee, Valérie Castellani and Frédéric Saudou, for their guidance and valuable expertise that was inspiring and motivating. Thanks to Nicolas Gadot and Hichem Mertani for their benevolence. They put me in touch with Christelle Peyron, from Pierre-Hervé Luppi team, who helped me, always with a smile, at different key stages of my project. I also want to acknowledge AniCan, in particular Bastien Kaniewski and Isabelle Puisieux, who have kindly agreed to develop and put back into operation almost an entire floor of the building so that I could conduct my experiments. They have therefore facilitated the implementation of this project, and I am grateful for that. Thanks to Roland, for taking care of my little animals. Also, thank you Jero for helping me when I was isolated at the 6th floor and thank you Ambroise for having relieved me of some manipulations this summer. On a more personal note, I would like to finally thank all my (past and present) colleagues, most of whom are also friends. They have contributed and still contribute to make the laboratory a place where it is pleasant to work, to laugh ... and to eat! Special mention to the "bureau du fond" that I am happy to join every morning. A big thank also to my friends for the moments spent together that allowed me to find a good balance between professional life (the PhD student life can completely absorb you) and personal life. Thank you for the trips, the dance classes, the shows, the dinners, and the adventurous hikes. Finally, I dedicate this thesis to my beloved family, who has always supported me and who believes in me more than I do. Without you, I would not have come this far. Ce mémoire de doctorat intitulé « Etude de Netrin-1 et de son récepteur DCC en tant que nouvelles pistes thérapeutiques contre la maladie de Parkinson » est une thèse sur article qui s’appuie sur la reproduction d’un article en préparation, fruit d’un travail de collaboration entre les laboratoires de Patrick Mehlen, Mart Saarma et Keqiang Ye, que je signe en 1er auteur. Le mémoire est rédigé en anglais et sera présenté publiquement le 12 décembre 2018 en vue de l’obtention du grade de Docteur. 4 Acknowledgements / Remerciements Je tiens à remercier les membres du jury, Dr. Fanny Mann, Dr. Merja Voutilainen, Prof. Emmanuel Moyse, Prof. Frédéric Saudou, Prof. Mart Saarma et Prof. Patrick Arrigo, d’avoir accepté d’évaluer ce travail. Merci également aux rapporteurs pour le temps consacré à la lecture et à l’évaluation du mémoire de thèse, malgré le délai quelque peu écourté. J’aimerais également remercier la fondation Michael J Fox (MJFF) et l’association France Parkinson pour avoir soutenu le projet de recherche présenté dans ce mémoire.
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