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Relation between fatty acid binding protein 4 and the biology of macrophagic vacuoles harboring Leishmania

Grant number: 18/07306-1
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): July 01, 2018
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Danilo Ciccone Miguel
Grantee:Mariana Borges Costa Brioschi
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/21129-4 - The role of fatty acid-binding proteins in the macrophage infection by Leishmania: a potential target for new drugs against leishmaniasis, AP.JP

Abstract

In Brazil, about 23,000 cases of leishmaniasis were reported between 2007 and 2016 per year. Therefore, this protozoosis still represents a significant problem for public health, and it is still very complex in terms of therapeutic options, since the drugs available in the country are toxic and require parenteral administration. Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania transmitted by the bite of infected phlebotomine female insects. In the vertebrate host, parasites infect several cells of the phagocytic mononuclear system, mainly macrophages, and remain in vacuoles parasitoforos as amastigotes where they modulate the environment to guarantee its survival. One of the strategies of survival is the uptake of nutrients from the host, e.g. fatty acids that will be incorporated into biosynthetic routes of the parasite. Several studies have shown that fatty acid binding proteins (FABPs) transport fatty acids to various cellular compartments in macrophages, a cell type in which FABP type 4 (FABP4) is abundant and controls the availability of lipid mediators and fatty acids in the cytosol. Because parasites are metabolically dependent on these molecules, this protein may exert an influence on the success of the infection. In addition, previous studies have shown that the number of FABP4 transcripts in macrophages is increased after infections by Leishmania (Leishmania) amazonensis. Therefore, the objective of this project is to determine FABP4 cellular localization in non-infected versus macrophages infected by L. (L.) amazonensis or L. (Viannia) braziliensis, species that survive in parasitophorous vacuoles with different characteristics. In addition, vacuolar morphological alterations will be evaluated in infections in the absence and presence of FABP4 specific inhibitor. In parallel, the levels of FABP4 transcripts in L. (V.) braziliensis infections will be quantified for comparison with results already obtained by the group for L. (L.) amazonensis-infected macrophages. Finally, we expect to establish conditions that are crucial for the survival of Leishmania - and perhaps dependent on the FABP4-mediated cellular signaling - opening perspectives for the search of new therapeutic targets against this infection. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BRIOSCHI, Mariana Borges Costa. Relation between type 4 fatty acid transport protein and the biology of macrophagic vacuoles infected with Leishmania. 2020. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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