Bolsa de PD em Bioquímica e Biologia Molecular de Tripanossomatídeos

Post-Doctoral Fellowship in Biochemistry and Molecular Biology of Trypanosomatids

• Resumo Summary

  A conversão de Cisteína (Cys) em Piruvato (Pyr) pode ser realizada por duas enzimas, uma Aspartato aminotransferase (ASAT) de amplo espectro de substrato, que admita dentre eles Cys, e uma Mercaptopiruvato Sulfotransferase (MPST). Pelas suas características, as ASAT de T. cruzi são candidatas a catalisar a reação de desaminação de Cys. Porém, apesar de existir no genoma de T. cruzi sequencias putativas para essas enzimas, até o momento não se tem dados na literatura que tenham mostrado essa via ativa. O objetivo deste projeto é confirmar a existência dessa via “direta” de produção de Pyr partir de Cys, assim como a possível existência de uma conexão dual entre Serina (Ser) e Cys: através da enzima cistationina-β-sintase, Ser poderia ser convertida em Cys (e posteriormente en Pyr) ou de forma reversa, através da enzima Cys-γ-liase (CGL) e posterior ação reversa da cistationina-β-sintase (CBS) a Cys poderia fornecer Ser, que também poderia fornecer Pyr mediante a Ser dehidrogenase. O objetivo deste projeto é explorar essas vias usando métodos de enzimologia, bioquímica, biologia molecular, metabolômica, bioenergética e edição gênica por CRISPR/Cas9.

  A vaga está aberta a brasileiros e estrangeiros. O selecionado receberá Bolsa de Pós-Doutorado da FAPESP no valor de R$ 9.047,40 mensais e Reserva Técnica equivalente a 10% do valor anual da bolsa para atender a despesas imprevistas e diretamente relacionadas à atividade de pesquisa.

  The conversion of Cysteine to Pyruvate can be carried out by two enzymes, a broad-spectrum substrate Aspartate aminotransferase (ASAT), which includes Cys among them, and a Mercaptopyruvate Sulfotransferase (MPST). Due to their characteristics, ASAT of T. cruzi are potential candidates to catalyze the Cystein deamination. However, despite a putative sequence for these enzymes in the T. cruzi genome, there is currently no literature data showing this pathway. The goal of this project is to confirm this “direct” pathway for Pyruvate production from Cystein, and the possible existence of a dual connection between Serine and Cystein: through the enzyme cystathionine-β-synthase, Serine could be converted to Cystein (and subsequently to Pyruvate) or conversely, through the enzyme Cystein-γ-lyase (CGL) and the reverse action of cystathionine-β-synthase (CBS), Cystein could provide Serine, which could also provide Pyruvate through a Serine dehydrogenase. The reason for the co-existence of both pathways is not clear, as it seems that both primarily function to provide Pyruvate, one using Ser as intermediates and the other using Cystein. The goal of this project is to explore these pathweays using methods in enzymology, biochemistry, metabolomics, bioenergetics and gene edition by CRISPR/Cas9.

  This opportunity is open to candidates of any nationality. The selected candidate will work at the University of São Paulo's Biomedical Sciences Institute (ICB-USP) in Brazil and receive a Post-Doctoral fellowship from the São Paulo Research Foundation (FAPESP) in the amount of R$ 9,047.40 monthly and a research contingency fund, equivalent to 10% of the annual value of the fellowship which should be spent on items directly related to the research activity.