University of Pittsburgh Department of Biological Sciences presents:
2019 Fall Seminar Series
Dr. Bibo Li
Cleveland State University
"Telomere and microbial pathogen virulence"
Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis, which is usually fatal without treatment. T. brucei proliferates in extracellular spaces in its mammalian host and elicit strong immune reactions. However, regular switching its major surface antigen, VSG, allows T. brucei to evade the host immune response and establish a long-term infection. Although T. brucei has more than 2,500 VSG genes in its genome, VSGs are only expressed from one of fifteen nearly identical VSG expression sites (ESs) in a strictly monoallelic manner. VSG ESs are large polycistronic transcription units transcribed by RNA Pol I and located at subtelomeres. VSG is the last gene in any ES and within 2 kb from the telomere. Antigenic variation is an important pathogenesis mechanism of a number of microbial pathogens that cause debilitating human diseases. Several pathogens also have their major surface antigen genes located at subtelomeres. We have identified several telomere-specific proteins in T. brucei, all play important roles in VSG switching regulation. Additionally, our work has shown that TbRAP1, a telomere protein, is an essential protein that plays a critical role in silencing all subtelomeric VSG genes except one. Our recent studies showed that TbRAP1 has unexpected nucleotide binding activities. Functional analyses indicate that these activities are crucial for VSG monoallelic expression, telomere integrity, and parasite viability. Our results suggest an unexpected and novel mechanism underlies TbRAP1’s role in silencing subtelomeric genes and may shed light on better understanding of similar mechanisms of antigenic variation in other microbial pathogens.
Monday, October 28, 2019
169 Crawford Hall
11:00 A.M.
10:50 A.M. refreshments
Host: Dr. Jon Boyle