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2002 - Instituto de Química - USP

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Alexan<strong>de</strong>r Henning UlrichLABORATÓRIO DA MODULAÇÃOARTIFICIAL DA DIFERENCIAÇÃONEURONALO interesse do nosso grupo é compreen<strong>de</strong>r aparticipação dos receptores purinérgicos nadiferenciação neuronal utilizando células-tronco<strong>de</strong>rivadas <strong>de</strong> teratocarcinoma murino como mo<strong>de</strong>lo.Nós estamos usando as técnicas <strong>de</strong> interferência <strong>de</strong>RNA (RNAi) e <strong>de</strong> SELEX para modular a expressão efunção <strong>de</strong>sses receptores durante a diferenciação.Estamos <strong>de</strong>senvolvendo inibidores capazes <strong>de</strong> induzira <strong>de</strong>gradação específica dos RNAm dos receptorespurinérgicos (estratégia <strong>de</strong> RNAi) ou capazes <strong>de</strong>interagir especificamente com seus produtosprotéicos (estratégia <strong>de</strong> SELEX). Através da técnica<strong>de</strong> RNAi, utilizando RNAs dupla-fita <strong>de</strong> variadostamanhos, estamos obtendo knock-outs funcionaispara os diferentes subtipos <strong>de</strong> receptores nasdiferentes etapas do processo <strong>de</strong> diferenciação. Coma técnica SELEX, que utiliza bibliotecas combinatórias<strong>de</strong> oligonucleotí<strong>de</strong>os, estamos <strong>de</strong>senvolvendoaptâmeros que se ligam nas formas abertas oufechadas dos canais iônicos dos receptorespurinérgicos inibindo ou ativando os mesmos.SummaryOur group´s interest is to un<strong>de</strong>rstand the role ofpurinergic receptors during neuronal differentiationusing a mouse embryonal carcinoma cell line as amo<strong>de</strong>l. The importance of these receptors is probedin vitro by constructing knock-outs by RNAIntereference (RNAi) or by selecting RNA aptamersthat inhibit or activate these receptors.PublicaçõesFaria, M.; Ulrich, H. (<strong>2002</strong>) The use of synthetic oligonucleoti<strong>de</strong>s as proteininhibitors and antico<strong>de</strong> drugs in cancer therapy: Accomplishmentsand Limits. Current Cancer Drug Targets 2, 355-368.Ulrich, H.; Mag<strong>de</strong>sian, M.H.; Alves, M.J.; Colli, W. (<strong>2002</strong>) In vitro selectionof RNA aptamers that bind to cell adhesion receptors of T. Cruzi andinhibit cell invasion. J. Biol. Chem. 277, 20756-62.Ulrich, H; Gameiro, A.M. (2001) Aptamers as tools to study disfunctionin the neuronal system. Curr. Med. Chem.-Central Nervous System Agents1, 125-32.Ulrich, H.; Alves, M.J.M; Colli, W. (2001) RNA and DNA aptamers aspotential tools to combat cell adhesion in disease. Braz. J. Med. Biol.Res. 34, 295-300.Tárnok, A; Ulrich, H. (2001) Characterization of the stress-induced calciumresponse in neuronal cell lines. Cytometry 43, 175-83.Mag<strong>de</strong>sian, Giordano, Ulrich, H, Juliano, M.A.; Schumacher, R.I.; Colli,W.; Alves, M.J.M. (2001) Infection by T. Cruzi: i<strong>de</strong>ntification of a parasiteligand and its host cell receptor. J. Biol. Chem. 276, 19382-9.<strong>Instituto</strong> <strong>de</strong> Química - Pesquisa 2001 - <strong>2002</strong> 8 Departamento Departamento <strong>de</strong> Química <strong>de</strong> FundamentalBioquímica

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