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TcCyp19 caracterization and evaluation of its role during cell infection by Trypanosoma cruzi

Grant number: 18/07766-2
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Start date: August 01, 2018
End date: September 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Sergio Schenkman
Grantee:Gregory Pedroso dos Santos
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:15/22031-0 - Cell signaling in Trypanosoma during host-parasite interaction, AP.TEM

Abstract

The present PhD project, entitled "Characterization of TcCyp19 and evaluation of its role during the cellular infection by Trypanosoma cruzi", was initiated by the joint work of Prof. Sergio Schenkman with Prof. Bradford Mcgwire of Ohio University who initiated studies showing the expression of cyclophilin 19 (TcCyp 19) in T. cruzi, the protozoan parasite that causes Chagas' disease. They verified that the TcCyp 19 is secreted by the replicative forms found in the insect triatomine vector being able to inactivate an antimicrobial peptide and that in the inactive form causes the signaling of the calcineurin in the parasites, leading to a greater infectivity. It has also been found that TcCyp19 is acetylated on the side chain of various lysines. Cyclophilins compose a family of very well conserved proteins between organisms. TcCyp 19 has great similarity with the cyclophilin A (Cyp A) found in mammals that acts among others in the cellular processes of inflammation in cardiac cells. In this research project we aim to study the role of TcCyp 19 during T. cruzi infection in mammalian cells in order to verify this protein could have some role in the inflammatory events of Chagas disease. More specifically we intend to: 1) determine the amounts of TcCyp19 expressed in the different stages of the parasite; 2) to verify whether it is secreted into the extracellular medium and into the cytosol of infected mammalian cells; 3) investigate the mechanisms involved, possibly acetylation, for its secretion; 4) to verify whether the presence of TcCyp19 in the cytosol or in the culture medium in some way affects survival, growth when the host cell is subjected to stresses that induce cell death. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
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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)
DOS SANTOS, GREGORY PEDROSO; ABUKAWA, FERNANDA MIDORI; SOUZA-MELO, NORMANDA; ALCANTARA, LAURA MARIA; BITTENCOURT-CUNHA, PAULA; MORAES, CAROLINA BORSOI; JHA, BIJAY KUMAR; MCGWIRE, BRADFORD S.; MORETTI, NILMAR SILVIO; SCHENKMAN, SERGIO. Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth. Cellular Microbiology, v. 23, n. 4, . (18/09948-0, 17/02416-0, 17/19303-4, 18/07766-2)
MALVEZZI, AMARANTA MUNIZ; ARICO, MIRELLA; SOUZA-MELO, NORMANDA; DOS SANTOS, GREGORY PEDROSO; BITTENCOURT-CUNHA, PAULA; HOLETZ, FABIOLA BARBIERI; SCHENKMAN, SERGIO. GCN2-Like Kinase Modulates Stress Granule Formation During Nutritional Stress in Trypanosoma cruzi. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, . (18/07766-2, 17/02416-0)