Search for phosphatidylserine translocators in Leishmania

• Grant number: 07/08358-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2008
• End date: September 30, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Lucile Maria Floeter-Winter
• Grantee: Marcos Gonzaga dos Santos
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 06/00019-0 - Biochemical and physiological aspects of Leishmania infection, AP.TEM

Abstract

When exposed on the outer leaflet of the plasmatic membrane, phosphatidylserine (PS) has an important role in the removal of apoptotic cells by the macrophage without a inflammatory response. It was proposed that Leishmania used the process to be phagocited by the macrophage. Efforts to obtain a knock-out Leishmania for phosphatidylserine synthesis did not result in the expected mutant, indicating this pathway must be essential to the parasite. In this project, we intend to determine the functional role of PS in the macrophage invasion and inactivation in Leishmania, by studying the enzymes involved in the PS transport across the membrane. To achieve this objective we will first identified the enzymes and then, mutants which are unable to expose PS, or that expose PS in all its life cycle will be obtained. The ability of these mutants to infect macrophages will be tested in standard in vitro macrophage infections, with only one mutant at a time, or in in vitro macrophage infections with both mutants at the same time. We intend to adopt L. (Viannia) braziliensis as a model as it seems to have active machinery for RNA interference, which makes it easier to suppress the expression of the studied gene, instead of classical knock-out. (AU)