Abstract
Leishmania is the protozoan responsible for leishmaniasis, a neglected disease that in Brazil causes about 100,000 new cases per year. In its life cycle, the parasite is found in the midgut of an insect or inside the phagolysosome in the macrophage of the mammalian host. The different stages of parasite life cycle influence the regulation of gene expression, which occurs at post-transcriptional level. Applying genomic, transcriptomic and metabolomic approaches, we will continue, in four subprojects, to study the thematic established by our group, determining and/or establishing new correlations between arginine metabolism and polyamine production in the parasite-host interaction. Thus, we intend to characterize parasites resistant to pentamidine and duramycin, target drugs in polyamine pathways (subproject A). To determine how the infection changes the miRNA profile of human or mice macrophages correlating with transcripts and metabolites profiles (subproject B). To use CRISPR/Cas9 to obtain null knockouts parasites of genes involved in arginine metabolism, confirming physiological roles and the location of their products (subproject C). To correlate sleep fragmentation and consequent alteration of the mounting of immune response against Leishmania infection in C57BL/6 mice, elucidating if there are changes in the profile of transcripts and miRNAs that influence the immune response and the course of infection (subproject D). The challenge of the four sub-projects is to correlate the different aspects of the parasite-host interaction by "omic" analysis, raising points that can be explore the understanding of biology and physiology, and for the design of new strategies to combat the parasite. (AU)
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