Part III: Current Research: Strategies for Cell Invasion and Intracellular Survival
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Trypanosoma cruzi and Leishmania are closely related intracellular protozoan parasites that cause serious diseases throughout the world. In the first part of this lecture, I will present background material on the biology of Trypanosoma cruzi and the history of its discovery as an important agent of human disease in Latin America. I will also discuss the main characteristics of the disease, and the current efforts to stop human transmission.
In the second part of this lecture, I will present background material on Leishmania, the intracellular protozoan parasites responsible for severe human pathology in several parts of the world. I will discuss the main disease forms, the history of identification of the causative agent and form of transmission, and recent discoveries that established important concepts in our understanding of this increasingly serious infectious disease.
In the third part of this lecture, I will discuss current work from our laboratory on mechanisms used by the intracellular parasites Trypanosoma cruzi and Leishmania to interact with mammalian cells. In addition to clarifying specific molecular strategies used by these parasites to infect and survive within host cells, these studies also led, in some instances, to unexpected insights on novel pathways regulating mammalian cell function.
Norma Andrews is currently a Professor and Chair of the Department of Cell Biology and Molecular Genetics at the University of Maryland. She received a B.S. degree in biology (1977) and a Ph.D. degree in biochemistry (1983) from the University of São Paulo, Brazil.
In 1990, after completing postdoctoral studies in the laboratory of Victor Nussenzweig at New York University, she was appointed Assistant Professor at Yale University where she remained until 2010.
Andrews was a Burroughs Wellcome New Investigator, a Burroughs Wellcome Molecular Parasitology Scholar and recipient of a NIH MERIT Award. Her laboratory has made numerous contributions to the cell biology of host-pathogen interactions, and discoveries in this area have led to the identification and functional characterization of a novel pathway of Ca2+-regulated lysosomal exocytosis in mammalian cells.
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Intracellular Parasitism by Trypanosoma cruzi and Leishmania, Norma Andrews General Reading Brener, Z. Biology of Trypanosoma cruzi . Annu. Rev. Microbiol 27:347-383, 1973.
Antoine JC, Prina E, Lang T, Courret N. The biogenesis and properties of the parasitophorous vacuoles that harbour Leishmania in murine macrophages. Trends Microbiol. 6: 392-401, 1998.
Sacks D, Kamhawi S. Molecular aspects of parasite-vector and vector-host interactions in leishmaniasis. Annu Rev Microbiol. 55: 453-483, 2001.
Andrade, L. O. and Andrews, N. W. The Trypanosoma cruzi -host cell interplay: Location, invasion, retention. Nature Reviews Microbiology 3: 819-823, 2005.
Andrews, N. W. Lysosomes and the plasma membrane: trypanosomes reveal a secret relationship. J. Cell Biol. 158: 389-394, 2002.
Tardieux, I., Webster, P., Ravesloot, J., Boron, W., Lunn, J. A., Heuser, J. and Andrews, N. W. Lysosome recruitment and fusion are early events required for trypanosome invasion of mammalian cells. Cell 71: 1117-1130, 1992.
Martinez, I., Chakrabarti, S., Hellevik, T., Morehead, J., Fowler, K. & Andrews, N. W. Synaptotagmin VII regulates Ca2+-dependent exocytosis of lysosomes in fibroblasts. J. Cell Biol. 148: 1141-1149, 2000.
Burleigh BA, Woolsey AM. Cell signalling and Trypanosoma cruzi invasion. Cell Microbiol. 4: 701-711, 2002.
Huynh, C, Sacks, D.L. and Andrews, N.W. A Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes. J. Exp. Med. 203: 2363-2375, 2006.