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FUNCTIONAL CHARACTERIZATION OF GIANT PROTEINS IN TRYPANOSOMATIDS AND INTERACTION WITH THE HOST CELL

Grant number: 18/03677-5
Support Opportunities:Regular Research Grants
Start date: April 01, 2018
End date: March 31, 2020
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Munira Muhammad Abdel Baqui
Grantee:Munira Muhammad Abdel Baqui
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

We have demonstrated in all genera of Trypanosomatidae family the presence of high molecular mass proteins (1000-4000 kDa) associated to the cytoskeleton and that despite having variations in the biochemical and molecular properties, the, function of most of these giant proteins remains unknown and may be related to the life cycle and with the cellular adaptations of each organism. In addition, recent proteomic analyzes of several protozoa indicated that there are a high number of high molecular weight proteins in these organisms and need to be investigated for their role in parasite biology.In Trypanosoma brucei, we have characterized the giant protein FAZ10 located at the Flagellar Adhesion Zone-FAZ and is involved in the correct orientation of the cleavage furrow and organelles positioning after cytokinesis. However, the elements that the giant protein is interacting in the FAZ still remain to be established. The silencing of FAZ10 compromises cellular proliferation leading to a defective cytokinesis in the parasite, furthermore to the detachment of the flagellum of the cell body. However, in T. cruzi, the giant protein is also located at the FAZ and its functional role is still unknown.In this project, we propose to identify the molecular partners that interact with FAZ10; to investigate the role of the giant proteins not yet characterized in T. brucei and T. cruzi, looking the protein interactions in the FAZ region and characterize the behavior of the giant T. cruzi protein during the infection and proliferation processes of the parasite in the host cell. Therefore, this project aims to understand the biological function of giant proteins in the parasites and may provide answers on the way of life of these organisms, helping in the future to development of new drugs to combat them. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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)
GACHET-CASTRO, CAMILA; MENDONCA TRAJANO-SILVA, LAYS ADRIANNE; BAQUI, MUNIRA MUHAMMAD ABDEL. Double Labeling Immunofluorescence using Antibodies from the Same Species to Study Host-Pathogen Interactions. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 173, . (10/19547-1, 18/03677-5)
DOMBROSKI, THAIS CAROLINE DALLABONA; PEIXOTO-SANTOS, JOSE EDUARDO; MACIEL, KARINA; BAQUI, MUNIRA MUHAMMAD ABDEL; VELASCO, TONICARLO RODRIGUES; SAKAMOTO, AMERICO CEIKI; ASSIRATI, JOAO ALBERTO; CARLOTTI, CARLOS GILBERTO; MACHADO, HELIO RUBENS; SOUSA, GLEICE KELLY DE; et al. Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis. Epilepsia, v. 61, n. 8, . (18/03677-5, 16/17882-4)
GACHET-CASTRO, CAMILA; FREITAS-CASTRO, FELIPE; GONZALES-CORDOVA, RAUL ALEXANDER; DA FONSECA, CAROL KOBORI; GOMES, MARCELO DAMARIO; ISHIKAWA-ANKERHOLD, HELLEN CRISTINA; BAQUI, MUNIRA MUHAMMAD ABDEL. Modulation of the Host Nuclear Compartment by Trypanosoma cruzi Uncovers Effects on Host Transcription and Splicing Machinery. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, . (18/03677-5, 10/19547-1, 18/01308-2)