Lucy GLOVER

Information

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.

Top 5 publications of the last 5 years

1. Faria J, Glover L, Hutchinson S, Boehm C, Field MC, Horn D. Monoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex. Nature communications. 2019;10(1):1-14. Epub 2019/07/11. doi: 10.1038/s41467-019-10823-8.

2. Glover L, Marques CA, Suska O, Horn D°. Persistent DNA damage foci and DNA replication with a broken chromosome in the African trypanosome. MBio. 2019;10(4):e01252-19. 

3. Mehnert AK, Prorocic M, Dujeancourt-Henry A, Hutchinson S, McCulloch R, Glover L. The MRN complex promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes. Nucleic Acids Res. 2021. Epub 2021/01/16. doi: 10.1093/nar/gkaa1265. 

4. Thivolle A, Mehnert AK, Tihon E, McLaughlin E, Dujeancourt-Henry A, Glover, L. (2021) DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice. PLOS Pathogens 17(11): e1010038. https://doi.org/10.1371/journal.ppat.1010038

5. McLaughlin E, Rubio Pena, Karinna, Dujeancourt-Henry A, Glover, L. (2022) Transcription dependent loss of an ectopically expressed variant surface glycoprotein during antigenic variation in Trypanosoma brucei. mBio 2022 Mar 1;e0384721. doi: 10.1128/mbio.03847-21.