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Alliance Française contre les Maladies Parasitaires


  Lucy Glover



microscope Trypanosome Molecular Biology (TMB) 
location Paris, Institut Pasteur
orcid 0000-0001-7191-6890 
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twitter @Glover_Tryplab

Scientific interests and projects

We research the host-pathogen relationship through understanding the mechanisms of DNA repair and allelic exclusion. Antigenic variation and immune evasion requires the DNA repair pathway and the strict monoallelic expression of a variant surface glycoprotein gene (VSG). To study the role of the DNA repair in antigenic variation, we use the I-SceI meganuclease system in Trypanosoma brucei (T. brucei) to temporally and spatially induce a single double-strand break (DSB) and study the dynamics of DSB repair and recombination. Our work has shown that the position of the DSB influences antigenic variation and repair pathway choice. Additionally, we use high-throughput functional RNAi librarys in trypanosomes to screen for factors required for VSG monoallelic control. This led to the identification of VEX1 (VSG EXclusion 1; Tb927.11.16920), a protein that controls monoallelic VSG gene expression.

Within the framework of ParaFrap our work is aimed at decoding the genetic basis for repair and recombination in T. brucei and identify cohorts of genes required for antigenic variation. By exploiting both a proteomics (SILAC and IP) and genomics (forward genetic screens) approach our goal is to determine the composition of the DNA repair factors that are essential for antigenic variation. We also aim understand the trypanosomes mechanisms of pathogenesis by understanding the role of VEX1 in controlling Metacyclic VSG expression in the Tsetse fly insect vector. Only a single mVSG is expressed in each cell, but the mechanism by which this expression is regulated and the factors required are unknown.