Application of CRISPR-Cas9 to interrogate novel gene functions in cutaneous melanoma

Abstract

I would like to dedicate this thesis to my parents, Robilson and Celia, my brother Yuri, and my husband Bruno, for being my inspiration and always encouraging me to do my best at all times.First, I would like to thank my supervisor Silvya, for giving me the opportunity of concluding my PhD, also for your guidance and support throughout the years. I would also like to thank my co-supervisor Patricia, for all advice and patience when answering my endless questions. I began the CRISPR journey because of you.To everyone in Skin Biology group, for your welcome and project discussions. Special thanks to Silvia Berlanga and Silvia Romano for advice on experimental work. Denisse, my IC Juliana and Daniele, who unfortunately already left the lab, for the laughter and friendship.I would also like to say that I was lucky to have Dave as a mentor/co-supervisor during my sandwich PhD at Sanger. This thesis would not have been possible without Dave´s generosity and I truly appreciate him giving me the opportunity of staying is his laboratory for over a year, despite crazy pandemic situation. Thank you for putting your trust in me. Your kindness and dedication for science is really inspiring.To everybody in Adam´s team for the amazing hospitality at Sanger. I was very fortunate to be surrounded by lovely people such as you all. Thanks to Alastair, Victoria, Manik, and Roy for all bioinformatic analyses and kindness answering my doubts. Thanks to Saskia, Jen, Andrea, and Vicky for making my stay in Cambridge so joyful. Thanks for all encouragement, also for sharing your knowledge and experience with me, especially Vicky for all discussions and many hours spent in cell culture. Also, many thanks to Sofia Chen, who allowed me to be part of her work and for her supervision during experiments. I am also grateful to all my collaborators. Thanks to Mariana Boroni and Natasha Jorge for analyses on TCGA data and David Fraser from Gene Editing team at Sanger, for sequencing analyses. Finally, I would like to thank my big family, my grandparents, aunts, uncles, and cousins, for all celebrated achievements. Especially my mom, dad and my brother for constant love and support. Also, my husband Bruno, for sharing all frustrations, highs, and lows and for always being my inspiration. I wouldn't be the person I am today without you. I respect and admire you all. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Brasil (CAPES) -Finance Code 001, CAPES-PRINT #88887.372178/2019-00, FAPESP #2017/04926-6, CNPq, and the Wellcome Trust Sanger Institute. "Nossas mentes possuem por natureza um insaciável desejo de saber a verdade" Padre Cícero RESUMO MATSUYAMA, L. S. A. S. Application of CRISPR-Cas9 to interrogate novel gene functions in cutaneous melanoma. 2021. 155 p. Tese (Doutorado em Ciências) -Faculdade