Biologia Molecular de Leishmanias

Lider (es): Luiz Ricardo Orsini Tosi
Telefone (s): (16) 3315-3117; (16) 3315-3159

Linha de pesquisa

Biologia de Patógenos

Linhas gerais/General outline

Nosso laboratório se ocupa do estudo da plasticidade genômica e sua relação a mecanismos de resposta ao dano no DNA no protozoário Leishmania.

Our laboratory deals with the genomic plasticity and gene expression control of the parasitic protozoan Leishmania.

Linhas de pesquisa/Reasearch areas

Os objetivos da linha de pesquisa desenvolvida em nosso laboratório visam à compreensão das vias de detecção e sinalização de danos no DNA do parasito protozoário Leishmania. Nossa hipótese é a de que a peculiariedades destas vias são determinantes da plasticidade do genoma deste organismo. Mais específicamente, investigamos as proteínas do parasito que poderiam compor um complexo homólogo ao grampo 9-1-1, encontrado em eucariotos superiores. Em células de mamíferos e em leveduras, o grampo 9-1-1 é central na resposta ao estresse replicativo pois sinaliza a parada do ciclo celular e participa no recrutamento da maquinaria de reparo do DNA. Encontramos que as proteínas LmHus1 e LmRad9 podem compor um possível homólogo de 9-1-1 e participar na resposta ao dano no DNA.

Our aim is to study the parasitic protozoan Leishmania. Our present investigations target the characterization of some aspects of the biology of this microorganism, such as drug resistance mechanisms and genomic plasticity. Part of our current projects examines how the genomic plasticity of this protozoan is explored as a means of regulating gene expression. Thus, by studying a gene localized in one end of the chromosome, we can verify the importance of the genomic context in its expression and in the control of DNA amplification and rearrangement mechanisms. Other projects focus on drug resistance mechanisms, especially those concerning antimonials, amphotericin B, and inhibitors of steroid synthesis. In this sense, we have already identified and characterized the gene LmYIP1, which participates in the intracellular vesicular traffic and confers resistance to terbinafine. The concern about the comparative analyses between species of the subgenera Leishmania and Viannia is present in most of the projects underway in our laboratory. Amplification studies on the loci related to drug resistance have demonstrated that formation of amplicons is a less common phenomenon in Viannia.

 

Sugestões de leitura/Suggestions for further reading

Nunes VS, Damasceno JD, Freire R, Tosi, LRO. 2011 The Hus1 homologue of Leishmania major encodes a nuclear protein that participates in DNA damage response. Molecular and Biochemical Parasitology, 177:65-69, 2011.

Peacock CS (+39 more authors including Tosi LRO) and Berriman N. 2007. Comparative genomic analysis of three Leishmania species that cause diverse human disease. Nature Genetics, 39:839-847.

Dias FC, Ruiz JC, Lopes WC, Squina FM, Renzi A, Cruz AK, Tosi LRO. 2007 Organization of H locus conserved repeats in Leishmania (Viannia) braziliensis correlates with lack of gene amplification and drug resistance. Parasitology Res., 3:667-676.

Squina FM, Pedrosa AL, Nunes VS, Cruz AK, Tosi LRO. 2007. Shuttle mutagenesis and targeted disruption of a telomere-located essential gene of Leishmania. Parasitology, 134:511-522.

Augusto MJ, Squina FM, Marchini JF, Dias FC, Tosi LRO. 2004. Specificity of modified Drosophila mariner transposons in the identification of Leishmania genes. Exp Parasitol., 108: 109-113.

Marchini JF, Cruz AK, Beverley SM, Tosi LRO. 2003. The H region HTBF gene mediates terbinafine resistance in Leishmania major. Mol Biochem Parasitol., 131: 77-81.