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LINUX Cluster Project

Lehrstuhl für Experimentelle Parasitologie


Institution

  • Name: Lehrstuhl für Experimentelle Parasitologie
  • Address: Lena-Christ-Str. 48, 82152 Planegg-Martinsried
  • Project Proposal Date: 2018-11-23 20:56:57

Abstract:

The extracellularly parasite Trypanosoma brucei is responsible for animal trypanosomiasis, also called nagana in cattle, and African trypanosomiasis, or sleeping sickness, in humans. The parasite is injected into the bloodstream of mammals by the tsetse fly, where it is constantly exposed to the host’s immune response. Thus, trypanosomes have evolved a coat of Variant Surface Glycoproteins (VSG) that shields the cell surface and invariant surface proteins from antibody attacks. Only one VSG is expressed at any given time, a tightly controlled mutually exclusive gene expression. Once recognized by the host’s antibodies, the parasites are able to switch to a different VSG in order escape the immune response. How a switch in VSG expression is triggered and how mutually exclusive VSG expression is ensured remains unknown. Intriguingly, in the genome transcriptionally repressed regions are marked by a unique DNA modification of thymidine called Base J. Base J, also referred to as a 5th base, is enriched across transcriptionally repressed genes but absent from the gene coding for the active VSG, implying a role in the mutually exclusive expression of VSG genes. During single molecule real time (SMRT) sequencing, DNA polymerases catalyse the incorporation of fluorescently labelled nucleotides into complementary nucleic acid strands. The arrival times and durations of the resulting fluorescence pulses yield information about polymerase kinetics and allow direct detection of modified nucleotides in the DNA template. The kinetics of Base J have been explored in Leishmania, a different Kinetoplastid, but not yet in T. brucei. We obtained SMRT sequencing data from T. brucei with 200x coverage and are aiming to pinpoint the exact locations of Base J in the genome, elucidating the role it might play in antigenic variation and the mechanisms behind the modification itself.