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Role of Pparp in Irradiation Mediated Intestinal Damage

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Role of Pparp in Irradiation Mediated Intestinal Damage Unicentre CH-1015 Lausanne http://serval.unil.ch Year : 2011 ROLE OF PPARP IN IRRADIATION MEDIATED INTESTINAL DAMAGE SAJIT THOTTATHIL OOMMEN SAJIT THOTTATHIL OOMMEN, 2011, ROLE OF PPARP IN IRRADIATION MEDIATED INTESTINAL DAMAGE Originally published at : Thesis, University of Lausanne Posted at the University of Lausanne Open Archive. http://serval.unil.ch Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). A ce titre, il est indispensable d'obtenir le consentement préalable de l'auteur et/ou de l’éditeur avant toute utilisation d'une oeuvre ou d'une partie d'une oeuvre ne relevant pas d'une utilisation à des fins personnelles au sens de la LDA (art. 19, al. 1 lettre a). A défaut, tout contrevenant s'expose aux sanctions prévues par cette loi. Nous déclinons toute responsabilité en la matière. Copyright The University of Lausanne expressly draws the attention of users to the fact that all documents published in the SERVAL Archive are protected by copyright in accordance with federal law on copyright and similar rights (LDA). Accordingly it is indispensable to obtain prior consent from the author and/or publisher before any use of a work or part of a work for purposes other than personal use within the meaning of LDA (art. 19, para. 1 letter a). Failure to do so will expose offenders to the sanctions laid down by this law. We accept no liability in this respect. Centre intégratif de génomique ROLE OF PPARβ IN IRRADIATION MEDIATED INTESTINAL DAMAGE Thèse de doctorat ès sciences de la vie (PhD) présentée à la Faculté de biologie et de médecine de l’Université de Lausanne par SAJIT THOTTATHIL OOMMEN Master de l'Université de Mysore (L'Inde)… Jury Prof. Nicolas Fasel, Président Prof. Béatrice Desvergne, Directrice de thèse Prof. Freddy Radtke, Expert Prof. Gisou Van Der Goot, Expert Lausanne 2011 ACKNOWLEDGEMENTS I would like to express my sincere gratitude to my supervisor, Prof. Beatrice Desvergne for giving me this opportunity to pursue my Ph.d in her laboratory at the Centre for Integrative Genomics (CIG). I especially thank her for her patience, understanding, guidance and all the constructive comments to improve my work. I would also like to thank Prof. Freddy Radtke, Prof. Gisou Van Der Goot, and Prof. Pierre Michetti for being part of the thesis committee and for their detailed review, constructive criticism and excellent advice for the preparation of my thesis. I would especially like to thank Prof. Edward Farmer for being the President of the mid-thesis committee, for all his valuable suggestions and for taking the extra efforts to coordinate the thesis evaluation. My special thanks to Prof. Nicolas Fasel for being the President of the thesis committee in the absence of Prof. Edward Farmer and for the valuable discussions and his suggestions. I am also thankful to my mentor - Prof. Bernard Thorens for his availability, his patient listening and his advises. My deep gratitude to Prof. Walter Wahli and Dr. Liliane Michalik for all their collaborations and their insightful comments during the PPAR group meetings. My heartfelt thanks to Prof. Mathias Chamaillard for the collaboration on their project that resulted in a publication. My sincere thanks to Federic Varnat for his advice on primary cell culture technique and several aspects of the irradiation model. I would also like to take this opportunity to thank Laurent Dubuquoy for his collaboration and very expert and insightful comments for the in-vivo experiments. I warmly thank Prof. Werner Held for his valuable advice and help with the Irradiation experiments. My sincere thanks to the members of the Transgenic Core Facility (TCF) and the Flow Cytometry Core facility (FCCF) at EPFL for their valuable help with the lentivirus production and FACS analysis respectively. I am grateful to all the members of the CIG with whom I could work in an amiable environment. My sincere thanks to the members of the Genomic Technologies Facility for their help with Q-PCR and microarray experiments especially Manuel, Alexandra, Melanie and Hannes. I also wish to thank Slyvian Pradervand and Leonore Wigger for their help with the statistical analysis of the microarray data. I also extend my warm thanks to Armelle Bauduret at the Genotyping facility and Catherine Roger at the Phenotyping facility for their invaluable support. This work would not have been complete without the help of Josianne Bonnetti, Librarian of the University. Thank you for your help with making available many of the research articles that I needed. My sincere thanks are due to Christian Freymond, for her well-organised management of the lab that helped in very smooth flow of my work and also to Gilles Boss for all sorts of technical help at the CIG. I also wish to thank Nourra Egger and Marlyne Berger at the Central stores for their kind help and generosity. I would like to thank Corinne Hanggeli, Gergely and Edgar for their excellent informatics support at the CIG. I am thankful to all the members at the animal facility particularly Patrick Gouait, Jose Huaman and Fabienne. Thanks for your help and support with maintaining the mice and all things I could learn from you. My sincere thanks to Carine for her valuable technical help and support all through out my thesis. I also wish to thank Elizabeth Joye, Genevieve, Maude, Fanny, Corinne Tallichet, Helene and Wanda who at one or the other time have offered their technical expertise and support. I am greatly indebted to Marlene Petit for all her help with the administrative work without which my stay here would have been impossible. I really appreciate her special efforts and excellent secretarial skills in getting around things relating to my resident permit extension for my stay here in the last few months. I would also like to extend my thanks to Loyse Rebord for her help with administrative matters. I am grateful to many of the new and old colleagues and friends for the good ambience at the floor. I am especially grateful to Christoph, Laure, Cristina, Federica, Aurelien, Alex. M, Alex. K, Radina, Silvia, Nicolas. R, Pipat, Ilenia for their patient guidance and discussions. I also thank Jean-Marc, Jose, Virginie, Ilhelm, Matthew, He Fu, Imtiaz, Marta, Gwendoline for time spent in lab in meaningful discussions. I specially cherish the friendship of Chiara and Maria-giovanna for the time spent in our lab. My special thanks to Nathalie, particularly for her help with the translation of the abstract in French. This work would be incomplete without the support of my friends in Lausanne – Shweta Tyagi, Shawon, Honey, Dhaval, Sandeep, Sujatha. Thanks to you for the homely feeling away from home. Thank you Shawon for all your help, support and your valuable suggestions. Words cannot convey the depth of my gratitude to you and I wouldn’t have made it if not for your friendship and support. This work would have been impossible without the prayers and support of my close friends Badri, Mary, Marc, Clara, Alice, Royson, Shaila, Lori, and Eva. Thank you for standing through the tough and testing times and for all your encouragement and invaluable support. Thank you Ibolya for the work in your lab in Hungary and to Betty for all your guidance that in a way laid the foundation for my work in Swiss. This work would be incomplete without the prayers and invaluable support of my friends at Westlake church, Lausanne. My heartfelt thanks to the entire congregation, particularly to Tom, Martin, Alphonse for your guidance and spiritual insight. My heartfelt thanks to Clive and Daniel for walking along with me in the tough times. I extend my special thanks to the Zindlers, Karen Rizzo, Brandon, Meredith, Brian, Carolyn, Jonathan Olivier, Jonathan Schuler, Gustavo, Suleidy for your friendship and encouragement. My special thanks to my friends in India – Sukumar anna, Sangeetha akka, Kiran uncle, Geetha Aunty, Soujanya, friends at Bethel fellowship and IISc BSF. Thanks for your invaluable support, friendship and prayers through out my entire work here. My heartfelt thanks to Prof. Cletus D’Souza for the constant encouragement, support, guidance and faith in me. I am so privileged to have you as my teacher. I owe my loving thanks to my Family – my parents for their faith in me and their hopes for me. Special thanks to my brother Sanjay and Sister in law- Liji for taking care of responsibilities at home and letting me stay focussed on my studies, and to my niece – AnnaMaria you are such a darling and blessing to all of us. There are many more people who have helped me in one or the other way through out this entire period of my thesis work and although I may not mention each of your names here, your help and support is warmly appreciated and my prayers for God’s blessings on your life. And last but not the least, my sincere and heartfelt thanks to Almighty God. Thank you Lord for this gift of life and your plans for me in Switzerland and for the miracles you have done. Thank you that you are a loving, faithful and everlasting God who keeps his Promises. Table of Contents TABLE OF CONTENTS Abbreviations ..............................................................................................................4 Summary .....................................................................................................................6 Résumé.........................................................................................................................7 Chapter I. Introduction..............................................................................................9 1. The Intestine ..........................................................................................................9 1.1. General organization of the intestine..............................................................9 1.1.1. Composition of the intestinal epithelium..............................................9 1.2. Signaling pathways in intestinal epithelial homeostasis ..............................12 1.2.1.
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