Molecular studies on Trypanosoma cruzi and its interaction with cells and factors from the host in vitro and in vivo

Abstract

Trypanosoma cruzi, the etiological agent of Chagas' disease, is a highly relevant microorganism from both medical and biological points of view. Although vectorial transmission is mostly under control in the Southern Cone, T cruzi transmission still prevails in Latin America where 15-16 million people are infected. Outbreaks of acute cases of Chagas' disease by oral infection have been reported in different areas of Brazil. Our group has extensively studied host cell invasion by trypomastigotes and amastigotes, an essential step in the establishment of infection in man and other vertebrate hosts. Oral infection has become the focus of our studies in the last years. The mechanisms of in vitro and in vivo T cruzi infection are beginning to be unveiled. Parasite molecules involved in host cell interactions are being analyzed regarding their expression in different developmental forms of T cruzi strains, and also as concerns their genomic organization and structure. In this project we intend to study, at the molecular level, the interaction of T cruzi with host cells and factors both in vitro and in vivo. The project involves the analysis of molecules previously identified by our group as well as the identification and characterization of new molecular and cellular components. Among our objectives is the identification of host cell receptors for the surface proteins of metacycIic trypomastigotes or amastigotes and the study of the intracellular traffic of T cruzi infective forms. We plan to use host cells transfected with different genes as well as co infection models with other trypanosomes and invasive bacteria. Concerning the metacycIic trypomastigote surface antigens, which are mainly encoded by mutagenic families, we intend to identify transcribed and translated genes by hybridizations with DNA micro-arrays and partial sequencing of proteins with mass spectroscopy, respectively. Recombination mechanisms, responsible for the generation of variants in these mutagenic families will be studied in parasites transfected with artificial and specially designed T cruzi chromosomes. These studies will bring new information on the mechanisms controlling gene expression in this parasite and on the evolution of multigenic families. Our project has a multi-disciplinary approach focused on the study of vertebrate host infection by T cruzi. The team of researchers has extensive experience in the fields of molecular and cell Biology, Immunology, Electron and Confocal microscopy and has been working together for many years, in a very productive way, engaged in joint research programmers. With the collaboration of fellow researchers from Brazil and abroad, we intend to make this project succeed. (AU)