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. et al. Monoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex. Nat Commun 10, 3023 (2019) doi: 10.1038/s41467-019-10823-8

2. Glover L, Marques CA, Suska O, Horn D. 2019. Persistent DNA damage foci and DNA replication with a broken chromosome in the African trypanosome. mBio 10:e01252-19. doi: 10.1128/mBio.01252-19

3. Hutchinson S, Glover L, Horn D. High-resolution analysis of multi-copy variant surface glycoprotein gene expression sites in African trypanosomes. BMC Genomics. 2016;17(1):806. Epub 2016/10/21. PubMed PMID: 27756224; PMCID: PMC5070307. doi: 10.1186/s12864-016-3154-8. 

4. Glover L, Hutchinson S, Alsford S, Horn D. VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes. Proc Natl Acad Sci U S A. 2016;113(26):7225-30. Epub 2016/05/27. PubMed PMID: 27226299; PMCID: PMC4932947. doi: 10.1073/pnas.1600344113. 

5. Glover L, Alsford S, Baker N, Turner DJ, Sanchez-Flores A, Hutchinson S, Hertz-Fowler C, Berriman M, Horn D. Genome-scale RNAi screens for high-throughput phenotyping in bloodstream-form African trypanosomes. Nat Protoc. 2015;10(1):106-33.  PubMed PMID: 25502887. doi: 10.1038/nprot.2015.005.