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Universidade Federal Do Rio De Janeiro Instituto De Bioquímica Universidade Federal do Rio de Janeiro Instituto de Bioquímica Médica MICHELLE LOPES RIBEIRO GUIMARÃES Estudo das proteases de micobactérias: clonagem, expressão e caracterização da protease recombinante HtrA2 produzida in vivo pelo Mycobacterium leprae V. I Rio de Janeiro *2007* Livros Grátis http://www.livrosgratis.com.br Milhares de livros grátis para download. LOMBADA GUIMARÃES GUIMARÃES LOPESMICHELLE RIBEIRO micobactérias: clonagem, expressão recombinante HtrA2 produzida in vivo pelo Myco e caracterização da protease Estudo das proteases de bacterium leprae UFRJ V. I Michelle Lopes Ribeiro Guimarães Estudo das proteases de micobactérias: clonagem, expressão e caracterização da protease recombinante HtrA2 produzida in vivo pelo Mycobacterium leprae Número de volumes: 1 Tese de Doutorado apresentada ao Programa de Pós- Graduação em Química Biológica, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, como parte dos requisitos necessários à obtenção do título de Doutor em Química Biológica. Orientador: Maria Cristina Vidal Pessolani Rio de Janeiro *2007* FICHA CATALOGRÁFICA Guimarães, Michelle Lopes Ribeiro.G.. Estudo das proteases de micobactérias: clonagem, expressão e caracterização da protease recombinante HtrA2 produzida in vivo pelo Mycobacterium leprae / Michelle Lopes Ribeiro Guimarães. Rio de Janeiro, 2007. x, 128 f.: il. Tese (Doutorado em Química Biológica) – Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica, 2007. Orientador: Maria Cristina Vidal Pessolani 1. Mycobacterium leprae . 2. Genômica Comparativa. 3. Proteases. 4. HtrAs – Teses. I.Pessolani, Maria Cristina Vidal (Orient.). II. Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. III. Título. Michelle Lopes Ribeiro Guimarães Estudo das proteases de micobactérias: clonagem, expressão e caracterização da protease recombinante HtrA2 produzida in vivo pelo Mycobacterium leprae Tese submetida ao corpo docente do Instituto de Bioquímica Médica da Universidade Federal do Rio de Janeiro, como parte dos requisitos necessários à obtenção do título de Doutor em Química Biológica. Rio de Janeiro, 23 de Julho de 2007. ______________________________________________ Dra. Maria Cristina Vidal Pessolani, Chefe do Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, FIOCRUZ. (Orientador) ______________________________________________ Dr. Robson de Queiroz Monteiro, Professor Adjunto, Instituto de Bioquímica Médica /ICB/UFRJ. ______________________________________________ Dr. Flavio Alves Lara, Pesquisador Assistente, Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, FIOCRUZ. ______________________________________________ Dr. Carlos Roberto Alves, Pesquisador Associado, Laboratório de Biologia Molecular de Doenças Endêmicas Manguinhos, Instituto Oswaldo Cruz, FIOCRUZ. ______________________________________________ Dr. Orlando Bonifácio Martins, Professor Adjunto, Instituto de Bioquímica Médica/ICB/UFRJ. (Suplente Interno) ______________________________________________ Dra. Maria Helena Feres Saad, Pesquisador Titular, Instituto Oswaldo Cruz, FIOCRUZ. (Suplente Externo) Este trabalho foi realizado no Laboratório de Microbiologia Celular, do Instituto Oswaldo Cruz da Fundação Oswaldo Cruz, sob a orientação da Doutora Maria Cristina Vidal Pessolani. Este trabalho foi financiado pelo CNPq e FAPERJ. Ao meu amado esposo Hugo Aos meus pais, Vitorino e Cleusa AGRADECIMENTOS O reconhecimento – substantivo e o reconhecer – verbo, ambos se constroem, primeiro com a desconstrução de realidades aparentemente reais e depois com o tempo – irremediável. Aprendi durante este trajeto, muitas técnicas, formas para tornar respostas, perguntas que nos pareciam mistérios aprendi que Ciência paradoxalmente é intuição, instinto, que conflitam com a razão e os protocolos. Qual não é nossa emoção e realização quando nos deparamos frente a um resultado próspero? No entanto, acredito que nosso maior aprendizado vem das pessoas que se deparam e passam por nosso caminho, é para todas estas pessoas que agradeço, pois participaram de forma inquestionável deste trabalho. ♦ Àquele que tudo criou e a nós não nos cabe definir, apenas crer em sua providência que sempre nos provê o necessário; ♦ Ao meu amor Hugo, sem você sou um ser incompleto, pela metade. Sou uma mulher plenamente realizada ao teu lado. Obrigada pela sua incondicional doação e amor. Paciência e confiança num futuro de felicidade; ♦ Ao meu pai, Vitorino, que sempre me incentivou e apoiou. Sem a sua participação em minha vida eu não estaria vivendo este momento agora; ♦ À minha mãe, Cleusa, por sempre ter me dado apoio em minhas decisões e, principalmente, por ser minha melhor amiga; ♦ Este é um agradecimento mais que especial à minha orientadora e amiga, Dra. Maria Cristina Vidal Pessolani por me acompanhar há mais de oito anos e formar meu caráter científico. Neste período, sempre se empenhou em apoiar, elogiar, aconselhar e repreender minhas atitudes equivocadas. Obrigada pela amizade, confiança, paciência, dedicação, e por ser um grande exemplo pra mim. Obrigada pela ajuda em todas as etapas desse trabalho; ♦ À Dra. Fernanda Portaro, do laboratório de Imunoquímica, Instituto Butantã, São Paulo, pela inestimável amizade, disponibilidade, incentivo. Obrigada por me acolher nas duas ocasiões em que estive em Sampa. Obrigada por abrir as portas do seu laboratório, disponibilizando recursos e pessoal, para agilizar meus experimentos. Minha tese não seria a mesma sem sua participação; ♦ À Eliana Blini Marengo, também do Instituto Butantã, por ser tão amiga e prestativa. Por me abrigar e me fazer sentir em casa. Por colaborar, participar e acreditar no meu trabalho; ♦ À Natália Pieranfeli dos Santos , aluna de iniciação científica da Dra. Fernanda Portaro, por sua dedicação, ajuda e eficiência; ♦ A todos do Centro Aplicado de Toxinologia, CAT, que me receberam tão bem e tornaram minha estada em São Paulo muito agradável. Obrigada a todos os que contribuíram para este trabalho se tornar realidade, de forma direta ou indireta; ♦ À Dra. Euzenir Nunes Sarno, pelo incentivo e amizade, tão importantes nesta jornada; ♦ À Dra. Eugênia Galo, pela generosidade e colaboração; ♦ Ao Dr. Sergio Antunes, pelas conversas e sugestões, ajuda e colaboração; ♦ À Dra. Maria Helena Saad, e aos demais chefes de laboratório, por sempre serem tão gentis e prestativos comigo; ♦ Ao professor Dr. Orlando O. Martins, pela revisão cuidadosa da minha tese, pelas sugestões sempre relevantes e pela amizade; ♦ Aos meus amigos de sala e cervejas, Elisa (Rock Balboa), Julio, Leonardo, descobri em vocês o valor da verdadeira amizade, minha jornada foi muito menos árdua pela companhia de vocês; ♦ Ás minhas amigas Luciana, Tatiana (minha amiga, ainda bronquinha), por sua ajuda em vários momentos e incentivo; ♦ Aos meus queridos amigos de labuta, que estão distantes apenas fisicamente, Cristiana e Renato, vocês são pessoas de fibra e merecem todo o sucesso e felicidade possível; ♦ À Patrícia, minha querida ex-aluna, pois sem a sua participação esta tese não teria sido a mesma; ♦ Aos colegas da sala 27, Adriano, André, Érika, Lucinéia, Márcia, Michel, a Érika (que o duende escondeu) pelos inúmeros momentos agradáveis de convivência; ♦ Aos meus colegas e amigos Milton, Adalberto, Harrison, Sidra, Viviane, Amanda, Mara, pelo companheirismo, carinho e ajudas; ♦ Ao Dr. José Augusto médico do Ambulatório Souza Araújo/Fiocruz/RJ, pela amizade, prestabilidade e gentilezas. Enfermeira Denise e demais componentes do ambulatório Souza Araújo/FIOCRUZ; ♦ Aos meus sogros, Sr. Agripino e Sra. Marlene, que deram a vida ao ser que mais amo, e por darem tanto apoio e carinho sempre. Eu ganhei não um sogro e uma sogra, mais sim, um pai e uma mãe; ♦ Aos meus avós maternos, Arnaldo e Izaura, em sua memória, e a toda a minha família pelo suporte carinhoso de sempre; ♦ Aos meus avós paternos, Vitorino, in memorian , e Luzia, pelo carinho, amor e exemplo de luta e amor pela vida; ♦ Ao meu gato Azinho, ou Zen gatinho, meu gato de guarda por toda a alegria e bem estar que causa e pela inseparável companhia durante esses 12 anos em que estamos juntos; ♦ Ao Sr. Salles, que sempre me socorreu com seu carinho fraternal e amizade; ♦ Aos funcionários da secretaria do programa de pós-graduação em Química Biológica, IBMQ, UFRJ, em especial para a Teresa, pelo apoio sempre solícito em todos os momentos; ♦ A todos os professores do Instituto de Bioquímica Médica, a coordenação do programa de pós- graduação, por formarem verdadeiros doutores e mestres e em particular pela solicitude sempre presente durante toda minha estada neste instituto; ♦ A todos os que trabalham na secretaria da hanseníase, pelas xérox e outros favores que me foram de grande valia; ♦ À Bené, Sr. Paulo, Solange, e todos os outros colaboradores, porque sem vocês este laboratório não funcionaria; ♦ A todos os outros amigos, que eu não citei aqui, mas que fazem parte do meu coração; ♦ Ao Instituto Pasteur, France, por ter financiado minha participação no curso “First Joint Pasteur Institute/Wellcome Trust Course on Genomics in South América”, realizado no Uruguai e a todos os que de alguma forma contribuíram para minha introdução ao mundo da Bioinformática; ♦ Ao LNCC por ter financiado minha participação na “ Conferência em Bioinformática: Global dialogues on emerging science and technology”, realizado em Petrópolis, Rio de Janeiro; ♦ Ao CNPq, por terem financiado este projeto, minha bolsa, além de outros benefícios; ♦ A FAPERJ por ter financiado este projeto. "Toda
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