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Effects of PRMT6 overexpression in the virulence levels of Leishmania

Grant number: 14/00220-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2014
Effective date (End): March 31, 2015
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Angela Kaysel Cruz
Grantee:Mateus Augusto Rodrigues
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Leishmaniasis is a prevalent disease in tropical and subtropical regions, affecting almost 90 million people worldwide. The absence of vaccines and chemotherapeutic treatments, which associate efficacy and low toxicity maintain the burden of the disease and allow about 2 million new cases each year. Rational search for targets and lead development to allow better chemotherapy includes understanding the parasite's molecular biology and peculiar pathways of genetic expression regulation. Therefore, investigation and characterization of molecules involved in this process have been conduct to unravel their potential role and effect in the parasite's virulence. Arginine methyltransferases (PRMTs) have been shown to be involved in the regulation of different events related to the control of gene expression, for it promotes methylation of arginine in proteins, such as histones and RNA-binding proteins (RBPs). Such post-translational modification alters action/interactions of target proteins. Therefore, indirectly PRMTs participate in the regulation of transcription, processing or transcripts stability, as shown in mammals and yeast. In trypanosomatids, PRMTs have been identified and partially characterized in T. brucei and were shown to be functionally similar to the orthologs. Tiago Ferreira has investigated, in our laboratory, the L. major PRMT7 and has demonstrated the existence of a negative correlation between the protein levels and the parasite's virulence. Our proposal is to investigate a putative effect of PRMT6 overexpression on virulence levels of L. major and L. donovani. We will analyze the parasite infectivity in vitro and in vivo comparing control transfectants with PRMT6 overexpressing parasites in each species.

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