{"id":1644,"date":"2021-08-22T20:06:48","date_gmt":"2021-08-22T22:06:48","guid":{"rendered":"https:\/\/sites.usp.br\/bmp\/?page_id=1644"},"modified":"2021-11-11T09:53:05","modified_gmt":"2021-11-11T12:53:05","slug":"pos-graduacao-gre","status":"publish","type":"page","link":"https:\/\/sites.usp.br\/bmp\/pos-graduacao-gre\/","title":{"rendered":"[P\u00f3s-gradua\u00e7\u00e3o] – GRE"},"content":{"rendered":"\t\t
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GRE<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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O Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biologia da Rela\u00e7\u00e3o Pat\u00f3geno-Hospedeiro receber\u00e1 candidatos interessados em aplicar a bolsas de doutorado direto atrav\u00e9s da iniciativa conjunta USP e FAPESP. Para mais informa\u00e7\u00f5es, clique no link: http:\/\/www.prpg.usp.br\/index.php\/pt-br\/gre-2\/usp-gre-2<\/a>.<\/div>

Orientadores eleg\u00edveis para esta iniciativa em particular e suas respectivas linhas de pesquisa est\u00e3o listados abaixo.<\/p><\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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\n\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\tProf. Ariel Mariano Silber\t\t\t\t<\/span>\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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O papel biol\u00f3gico de amino\u00e1cidos e seus metab\u00f3litos derivados em Trypanosoma cruzi.<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Diversos estudos t\u00eam descrito a import\u00e2ncia dos amino\u00e1cidos na biologia de diferentes protozo\u00e1rios como o Trypanosoma cruzi<\/em>, o agente etiol\u00f3gico da doen\u00e7a de Chagas. Os amino\u00e1cidos, al\u00e9m de atuarem na s\u00edntese prot\u00e9ica e no metabolismo energ\u00e9tico, possuem diversas outras fun\u00e7\u00f5es no parasito. Dentre eles, vale a pena mencionar a diferencia\u00e7\u00e3o entre formas replicativas e infectivas, o sustento energ\u00e9tico da invas\u00e3o das c\u00e9lulas do hospedeiro mam\u00edfero, o estabelecimento da infec\u00e7\u00e3o e a resist\u00eancia a diferentes tipos de estresse aos quais o parasita \u00e9 naturalmente submetido ao longo do seu ciclo biol\u00f3gico, tais como o estresse osm\u00f3tico, t\u00e9rmico, oxidativo e nutricional. At\u00e9 agora tem-se avaliado o papel de v\u00e1rios dos amino\u00e1cidos, de maneira individual, nesses processos. Por\u00e9m, ainda n\u00e3o h\u00e1 um trabalho integrado e sistem\u00e1tico que permita avaliar o papel das principais vias metab\u00f3licas envolvendo amino\u00e1cidos, nem as suas poss\u00edveis intera\u00e7\u00f5es. Este projeto tem o prop\u00f3sito de: (1) Construir um mapa do metabolismo dos amino\u00e1cidos com foco naqueles com fun\u00e7\u00f5es na bioenerg\u00e9tica de\u00a0T. cruzi<\/em>, incluindo a defini\u00e7\u00e3o de auxotrofias para estes metab\u00f3litos. (2) Avaliar para todos os amino\u00e1cidos a capacidade de: i) induzir s\u00edntese de ATP, H2O2, explos\u00e3o respirat\u00f3ria e potencial de membrana mitocondrial, ii) diferencia\u00e7\u00e3o, iii) sustentar a invas\u00e3o celular, iv) resist\u00eancia a estresse oxidativo, t\u00e9rmico, nutricional, ac\u00eddico e \u00e0 toxicidade por ac\u00famulo de NH4+, v) modular o ciclo celular, a autofagia e a morte celular programada sob estresse metab\u00f3lico. (3) Avaliar, para os amino\u00e1cidos que apresentem alguma das funcionalidades descritas em (2), o papel funcional de enzimas do seu metabolismo, assim como o efeito da sua inibi\u00e7\u00e3o qu\u00edmica ou superexpress\u00e3o em diferentes aspectos da biologia do parasito mencionadas em (2). (4) Realizar um estudo comparativo entre diferentes est\u00e1gios das atividades das distintas vias metab\u00f3licas de amino\u00e1cidos por metabol\u00f4mica dirigida (targeted metabolomic). (5) Desenvolver mediante CRISPR\/Cas9 linhagens nocaute para as enzimas mais relevantes no metabolismo de amino\u00e1cidos de vias metab\u00f3licas cr\u00edticas para os diferentes aspectos da biologia do parasita mencionados em (2) com o intuito de avaliar os seus poss\u00edveis efeitos relacionados com o potencial terap\u00eautico. Avaliar por metabol\u00f4mica o efeito da supress\u00e3o g\u00eanica ou do tratamento com os inibidores sobre o perfil metab\u00f3lico das c\u00e9lulas. (6) Avaliar o impacto do metabolismo de amino\u00e1cidos na administra\u00e7\u00e3o dos n\u00edveis intracelulares de NH4+, e na produ\u00e7\u00e3o de amino a\u00e7\u00facares e glicoconjugados.<\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\tProf. Carsten Wrenger\t\t\t\t<\/span>\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Drug discovery contra doen\u00e7as infecciosas humanas<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Doen\u00e7as infecciosas s\u00e3o uma amea\u00e7a a humanidade e atualmente seus agentes patog\u00eanicos est\u00e3o se espalhando geograficamente devido \u00e0 globaliza\u00e7\u00e3o e ao desenvolvimento de resist\u00eancia \u00e0s drogas dispon\u00edveis. A resist\u00eancia aos f\u00e1rmacos dispon\u00edveis atualmente est\u00e1 ocorrendo em quase todos os pat\u00f3genos e portanto h\u00e1 uma urgente necessidade de descobrir novo alvos terap\u00eauticos e\/ou novas classes de alvos. Neste projeto o foco ser\u00e1 a descoberta de novos pr\u00f3-f\u00e1rmacos explorando as vias de bioss\u00edntese das vitaminas B1\/B6 dos pat\u00f3genos humanos: Plasmodium falciparum<\/i>, o parasita respons\u00e1vel por causar a mal\u00e1ria severa, e a bact\u00e9ria multi-resistente\u00a0Staphylococcus aureus<\/i> MRSA. Compostos ser\u00e3o identificados e desenhados de acordo com avalia\u00e7\u00f5es baseadas nas estruturas cristalogr\u00e1ficas das respectivas enzimas envolvidas na bioss\u00edntese das vitaminas B1\/B6, visando a incorpora\u00e7\u00e3o dos compostos no metabolismo do pat\u00f3geno. Portanto os novos compostos buscar\u00e3o envenenar as enzimas dependentes das vitaminas como co-fatores. Ensaios complementares envolver\u00e3o o uso de linhagens celulares humanas, assim como suas respectivas linhagens transg\u00eanicas super expressando receptores nucleares para xenobi\u00f3ticos, a fim de reportar poss\u00edveis intera\u00e7\u00f5es com o hospedeiro.<\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\tProf. C\u00e9lia Regina da Silva Garcia\t\t\t\t<\/span>\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Gen\u00f4mica Funcional em Plasmodium<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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The elucidation of cell cycle and development control mechanisms of Plasmodium, the etiological agent of malaria, is crucial for development of new strategies for disease control. In this way, different ways of control either cell cycle or parasite development are propose to be studied in this project.
Since our data generated in recent last years, including the identification of serpentine receptors, known in participating in a variety of cell processes, usually known as drug targets, will be better analyzed. Characterizing the RACK protein (receptor of activated protein kinase C) is also very important, whereas protein kinase C has not been found in Plasmodium falciparum.
Moreover, the melatonin signaling pathway has bring us information about the participation of ubiquitin-proteasome system and protein kinase 7 as molecular effectors. Finally, detoxification mechanisms of heme in malaria parasites through hemeoxigenase will also be here evaluated.
These proposed sub-projects enclose a range of cellular processes that participate in\u00a0\u00a0 development and proliferation control of malaria parasite responsible for the most severe form of the disease, Plasmodium falciparum providing a contribution to knowledgement of diverse biological processes that enclose signaling pathways, gene expression control, cellular metabolism and others that participate in an indirect way.<\/p><\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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\n\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\tProf. Lu\u00eds Carlos de Souza Ferreira\t\t\t\t<\/span>\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Descoberta de ant\u00edgenos e desenvolvimento de m\u00e9todos de diagn\u00f3stico sorol\u00f3gico e estrat\u00e9gias vacinais contra o V\u00edrus Zika (ZIKV)<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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O presente pedido de financiamento para projeto de pesquisa tem\u00e1tico tem como principal objetivo o financiamento de pesquisas relacionadas ao V\u00edrus Zika (ZIKV) atualmente em andamento nos Laborat\u00f3rios de Virologia (LV) e Desenvolvimento de Vacinas (LDV) da USP. O trabalho est\u00e1 centrado em quatro pontos principais, a se saber: I) gera\u00e7\u00e3o e utiliza\u00e7\u00e3o de ant\u00edgenos recombinantes derivadas do ZIKV para uso em estrat\u00e9gias vacinais e desenvolvimento de m\u00e9todos de diagn\u00f3stico sorol\u00f3gicos espec\u00edficos; II) desenvolvimento de diferentes modelos experimentais in vitro e in vivo, assim como marcadores, que permitam avaliar e monitorar a imunidade induzida pelo ZIKV e a imunidade protetora conferida por formula\u00e7\u00f5es vacinais; III) desenvolvimento e teste de formula\u00e7\u00f5es vacinais voltadas para o controle da infec\u00e7\u00e3o pelo ZIKV, incluindo diferentes ant\u00edgenos, adjuvantes, e vias de inocula\u00e7\u00e3o; e (IV) desenvolvimento de testes sorol\u00f3gicos espec\u00edficos a partir de ant\u00edgenos recombinantes derivados do ZIKV. O trabalho ser\u00e1 feito em parceria com diferentes grupos de pesquisa na USP, e fora dela, com \u00eanfase no Instituto Butantan, Fiocruz e Instituto Pasteur. Os LV e LDV tem experi\u00eancia no desenvolvimento de ant\u00edgenos, desenvolvimento de formula\u00e7\u00f5es vacinais e testes de diagn\u00f3stico contra o V\u00edrus Dengue (DENV) e outros v\u00edrus e pat\u00f3genos. O trabalho proposto est\u00e1 respaldado na experi\u00eancia demonstrada pelos grupos proponentes nos \u00faltimos anos. Al\u00e9m disto, resultados obtidos no contexto do projeto j\u00e1 resultaram em publica\u00e7\u00f5es, pedidos de patente e descobertas cient\u00edficas que vem sendo utilizadas por diferentes institui\u00e7\u00f5es de pesquisa no pa\u00eds e no exterior. Os resultados esperados trar\u00e3o impactos importantes tanto para o melhor entendimento da sorologia da infec\u00e7\u00e3o pelo ZIKV como em pesquisas que resultem no desenvolvimento de formula\u00e7\u00f5es vacinais pass\u00edveis de serem utilizadas em seres humanos. Espera-se que os resultados a serem alcan\u00e7ados tenham desdobramentos acad\u00eamicos significativos e resulte no desenvolvimento de tecnologias com aplica\u00e7\u00e3o a curto e m\u00e9dio prazo no pa\u00eds.<\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\tProf. Marcelo Urbano Ferreira\t\t\t\t<\/span>\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Bases cient\u00edficas para a elimina\u00e7\u00e3o da mal\u00e1ria residual na Amaz\u00f4nia Brasileira <\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Com 143.910 casos confirmados por laborat\u00f3rio e 41 mortes relacionadas \u00e0 mal\u00e1ria em 2014, o Brasil tem hoje o menor fardo de mal\u00e1ria em 35 anos, com transmiss\u00e3o praticamente limitada \u00e0 Bacia Amaz\u00f4nica. A natureza focal da transmiss\u00e3o da mal\u00e1ria no Brasil sugere que os esfor\u00e7os de elimina\u00e7\u00e3o exigir\u00e3o uma minuciosa prioriza\u00e7\u00e3o de alguns bolsos residuais da mal\u00e1ria. Combinamos abordagens epidemiol\u00f3gicas cl\u00e1ssicas, para caracterizar fatores de risco e metas de interven\u00e7\u00e3o, com an\u00e1lises de gen\u00e9tica\/gen\u00f4mica populacional de parasitas com o objetivo final de melhorar estrat\u00e9gias atuais para controle e elimina\u00e7\u00e3o de mal\u00e1ria no Brasil. Nossos estudos de campo na principal \u00e1rea end\u00eamica do Brasil (Vale do Juru\u00e1, perto da fronteira com o Peru, que representa 20% de todas as infec\u00e7\u00f5es neste pa\u00eds) s\u00e3o complementados com modelagem matem\u00e1tica de diferentes cen\u00e1rios de elimina\u00e7\u00e3o de mal\u00e1ria. Concentramo-nos em dois desafios principais para a elimina\u00e7\u00e3o da mal\u00e1ria: (a) a presen\u00e7a de infec\u00e7\u00f5es assintom\u00e1ticas com parasitemias baixas que est\u00e3o frequentemente abaixo do limiar de detec\u00e7\u00e3o de t\u00e9cnicas diagn\u00f3sticas dispon\u00edveis, criando um grande e n\u00e3o detectado reservat\u00f3rio de infec\u00e7\u00e3o e (b) a manuten\u00e7\u00e3o de altas densidades de vetores que resultam de novos criadouros de mosquitos feitos pelo homem (lagos de peixes abertos em todo o Vale do Juru\u00e1 para aquicultura comercial).<\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Como caracter\u00edsticas comuns e divergentes da resposta replicativa ao estresse moldam a biologia dos parasitas TriTryp?<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Trypanosoma cruzi<\/i>,\u00a0Trypanosoma brucei<\/i>\u00a0and\u00a0Leishmania<\/i>\u00a0spp. (tritryps) present different in their life cycles as well as in their strategy for vertebrate infection. These differences in core biology are influenced by the ability of the parasites to maintain and alter their genome, leading to adaptive changes in gene expression. Gene expression is organized almost exclusively as polycistronic transcription, where every gene is expressed from one of a small number of a multigene units meaning that RNA Polymerase needs to traverse unusually long distances. The nature of transcription in each genome must predispose the parasites to pronounced replication stress due to collision between the replication and transcription machineries, leading to DNA replication fork stalling. In such stress conditions, the halted DNA fork is recognized by kinases ATM and ATR, which initiate a signaling cascade that mediates the appropriate response to the blockade. The nature of the replication stress signaling or the mechanisms of response are not the same in the tritryps and differences in genome architecture in the tritryps may be related to differing strategies used to resolve replication stress due to clashes with transcription. Specifically, it might be predicted that\u00a0T. brucei<\/i>\u00a0activates dormant origins in conditions of stress, whereas\u00a0T. cruzi<\/i>\u00a0and\u00a0Leishmania<\/i>\u00a0resolve the stalled forks using recombination\/amplification. We aim to determine if replication-transcription clashes are the main cause of the different genome architectures, and to reveal and compare the strategies used to resolve a stalled DNA replication forks in the parasites.<\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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<\/div>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

GRE O Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biologia da Rela\u00e7\u00e3o Pat\u00f3geno-Hospedeiro receber\u00e1 candidatos interessados em aplicar a bolsas de doutorado direto atrav\u00e9s da iniciativa conjunta USP e FAPESP. Para mais informa\u00e7\u00f5es, clique no link: http:\/\/www.prpg.usp.br\/index.php\/pt-br\/gre-2\/usp-gre-2. Orientadores eleg\u00edveis para esta iniciativa em particular e suas respectivas linhas de pesquisa est\u00e3o listados abaixo. Prof. Ariel Mariano Silber O[…]<\/a><\/p>\n","protected":false},"author":1200,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"elementor_header_footer","meta":{"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-1644","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/pages\/1644","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/users\/1200"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/comments?post=1644"}],"version-history":[{"count":4,"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/pages\/1644\/revisions"}],"predecessor-version":[{"id":5341,"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/pages\/1644\/revisions\/5341"}],"wp:attachment":[{"href":"https:\/\/sites.usp.br\/bmp\/wp-json\/wp\/v2\/media?parent=1644"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}