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Biochemical, physiological and functional genomics studies of Leishmania-macrophage interaction


The biology of parasites belonging to Leishmania genus offers unique features as model for studying the host - pathogen interaction. Here we propose three sub-projects to study biochemical and physiological aspects of this interaction, primarily upon infection of macrophages in the mammalian host. The objectives of the project are: To correlate the sub-cellular localization of arginase in Leishmania glycosome with its possible functional role in the replication of the parasite and maintenance of infection. To demonstrate the existence of a competition or a cross-regulation between the arginase from the parasite and the nitric oxide synthase (iNOS) from the macrophage. To evaluate the transport of L-arginine at different life stages of the parasite. To characterize the effect of melatonin produced by the mammal in the infection. To determine the transport of phospholipids in Leishmania and their importance in maintaining infection. The development of the proposed sub-projects will be in charge of two Post-Doc's (Marcos Gonzaga dos Santos and Maria Fernanda Laranjeira da Silva), 1 PhD student (Emerson Martins) and two under-graduated students (to be selected). Will take part of the project the technicians Ricardo A. Zampieri and Sandra M. Muxel. There is also the establishment of an important collaborative effort with the Laboratory of Chronopharmacology (IB- USP) coordinated by Prof. Regina P. Markus, to study how the Leishmania infection induces changes in the expression of host cells genes and how these cells respond to the signal. The understanding of this relationship may allow the design of effective actions in control of leishmaniosis. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MUXEL, SANDRA MARCIA; LARANJEIRA-SILVA, MARIA FERNANDA; ZAMPIERI, RICARDO ANDRADE; FLOETER-WINTER, LUCILE MARIA. Leishmania (Leishmania) amazonensis induces macrophage miR-294 and miR-721 expression and modulates infection by targeting NOS2 and L-arginine metabolism. SCIENTIFIC REPORTS, v. 7, MAR 9 2017. Web of Science Citations: 26.
MUXEL, SANDRA MARCIA; LARANJEIRA-SILVA, MARIA FERNANDA; CARVALHO-SOUSA, CLAUDIA EMANUELLE; FLOETER-WINTER, LUCILE MARIA; MARKUS, REGINA P. The RelA/cRel nuclear factor-B (NF-B) dimer, crucial for inflammation resolution, mediates the transcription of the key enzyme in melatonin synthesis in RAW 264.7 macrophages. Journal of Pineal Research, v. 60, n. 4, p. 394-404, MAY 2016. Web of Science Citations: 22.
LARANJEIRA-SILVA, MARIA FERNANDA; ZAMPIERI, RICARDO A.; MUXEL, SANDRA M.; FLOETER-WINTER, LUCILE MARIA; MARKUS, REGINA P. Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism. Journal of Pineal Research, v. 59, n. 4, p. 478-487, NOV 2015. Web of Science Citations: 18.

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