Protein secretion in Trypanosoma

• Grant number: 17/02416-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2017
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Sergio Schenkman
• Grantee: Normanda Souza Melo
• 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 objective of this postdoctoral project is to identify and characterize the components involved in the secretion of glicosyl-phosphatidylinositol (GPI) anchored proteins of T. cruzi. This is an exploratory project, in collaboration with Dr. Mark Field of the University of Dundee, who is a collaborator of this project. He has extensive experience in describing intracellular protein trafficking in T. brucei (Leung, Riley et al., 2011, Alsford, Field et al., 2013). One of the aims s related to the identification and functional characterization of the proteins of the p24 family, involving traffic from the endoplasmic reticulum to the Golgi. The other, to be performed in parallel contemplate the characterization of the ubiquitination/deubiquitination system in T. cruzi formed by deubiquitinase Usp33 and the ring protein Rbx1, described as important in endocytosis of surface proteins of T. brucei (Zolter et al., 2015, No press, PlosPathog). In a specific way we will look for: 1) the generation of T. brucei lineages for RNAi of p24 proteins and to analyze the parasite phenotype for the expression of surface proteins; 2) characterization of the complexes formed with T. cruzi Usp33 and Rbx1 proteins after insertion of tagged proteins by mass spectrometry; 3) generate superexpressor lines or T. cruzi knockouts of deUb proteins. (AU)

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)

VASCONCELOS, CAMILLA IOSHIDA; CRONEMBERGER-ANDRADE, A.; SOUZA-MELO, NORMANDA; MARICATO, JULIANA TERZI; XANDER, PATRICIA; BATISTA, WAGNER LUIZ; SOARES, RODRIGO PEDRO; SCHENKMAN, SERGIO; TORRECILHAS, ANA CLAUDIA. Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2021, SEP 24 2021. (19/15909-0, 20/07870-4, 17/02416-0)

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, APR 16 2020. (18/07766-2, 17/02416-0)

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, DEC 2020. (18/09948-0, 17/02416-0, 17/19303-4, 18/07766-2)