Phosphatidylinositol regulation of antigenic variation in trypanosomes
Dr. Igor Cestari, Center for Infectious Disease Research
Monday, April 18, 2016
Science and Engineering 2 Building, Room 302
Antigenic variation is a mechanism by which many protozoan, bacterial, and viral pathogens evade the host immune system. Trypanosoma brucei, a protozoan parasite that causes human and animal disease in Africa, evades the host antibody response
by periodically changing its surface coat of variant surface glycoproteins (VSGs). T. brucei expresses only one VSG gene at a time out of hundreds of possible VSG genes and changes the particular VSG being expressed by either transcriptional switch or recombination. The mechanisms regulating these processes are poorly understood. I recently found that the phosphatidylinositol pathway
plays a role in controlling VSG expression and switching by epigenetic regulation of telomere silencing. These data imply that a signal transduction pathway may regulate VSG gene transcription and switching and provide a new framework for understanding the regulation of antigenic variation in T. brucei. Since many genes involved in this process are essential for T. brucei infection, this pathway is rich with potential targets for new antiparasitic chemotherapies.
Dr. Cestari is a staff scientist at the Center for Infectious Disease Research in Seattle, WA. His work focuses on determining how trypanosomes evade the host immune response to cause disease and on developing chemotherapies against diseases caused by these parasites. He obtained his MSc and PhD from the Oswaldo Cruz Institute (Rio de Janeiro), where he studied how Trypanosoma cruzi evades the human complement system. During this period he was awarded a fellowship to conduct part of his graduate work at the Cellular and Molecular Immunology Research Centre (London) and the MRC Immunochemistry Unit (Oxford). Dr. Cestari joined the Center for Infectious Disease Research in 2010 as a postdoctoral scientist. He currently studies the regulation of antigenic variation, which is the main mechanism of host immune evasion by T. brucei, and explores the potential of enzymes involved in this process as new drug targets. In collaboration with GlaxoSmithKline, he has also identified new antiparasitic inhibitors with potential for further drug development efforts.
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