I am a first year graduate student who is completing a laboratory rotation in Dr. Fernando Villalta's laboratory in the Division of Biomedical Sciences. During my rotation I decided to join his laboratory because I became interested in the research being conducted in his laboratory in the area of cell and molecular biology of Trypanosoma cruzi-host cell interactions. T. cruzi is a major human pathogen that affects millions of people and causes Chagas' disease. This heart disease leads to cardiac arrest followed by death. Despite the mortality and morbidity caused by this parasite no effective chemotherapeutic agent or immunoprophylaxis has been found. The focus of this research is to identify trypanosome and mammal host genes that mediate and control the interactions between T. cruzi and mammalian host cells. This research program includes molecular analysis of genes encoding trypanosome ligands and host cell receptors for invasive trypanosomes in addition, this research also focuses on cloning non- essential genes of mammalian cells that regulate T. cruzi infection. Our laboratory has identified, cloned and sequenced the gene coding for a gp83 trans-sialidase of the Family 2 of the large multi-gene family of trans-sialidases that is expressed on the surface of invasive trypomastigote forms of T. cruzi that binds to mammalian cells in a ligand-receptor interaction manner and appears to mediate trypanosome entry. Our laboratory has also identified a surface 74 kDa glycoprotein which is expressed on the surface of mammalian cells that binds to the gp83 trans-sialidase of trypomastigotes and appears to function as a receptor for T. cruzi. This 74 glycoprotein is expressed on the surface of cells that can be invaded by T. cruzi but not on cells that cannot be invaded by T. cruzi. In addition this molecule binds to invasive trypomastigote forms of T. cruzi but not to non-invasive forms of T. cruzi. Cross-linking studies indicate that the radioiodinated gp83 trans- sialidase cross links to a 74 kDa glycoprotein expressed on the surface of mammalian cells that can be invaded by T. cruzi trypomastigotes. Recently our laboratory has initiated the molecular cloning of the gene coding for the host 74 kDa glycoprotein. I just became particularly interested in the research project involving cloning, sequencing, expressing and purifying the recombinant 74 kDa protein. I am also interested in studying the binding of the recombinant host protein to T. cruzi and to test the ability of the 74 kDa protein to function as a receptor for T. cruzi by transfecting mammalian cell lines which cannot be invaded by T. cruzi. In support of this hypothesis I would expect that transgenic mice in which the gene coding for the 74 kDa protein was knocked-out would be resistant to T. cruzi infection. I am particularly interested in these research topics because they will contribute to the establishment of the molecular basis of T. cruzi recognition by mammalian cells that promotes trypanosome entry and may facilitate molecular intervention in T. cruzi infection.
