@article{BatramJonesJanzenetal.2014,
  author    = {Batram, Christopher and Jones, Nivola G. and Janzen, Christian J. and Markert, Sebastian M. and Engstler, Markus},
  title     = {Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei},
  series = {eLife},
  volume    = {3},
  journal   = {eLife},
  number    = {e02324},
  issn      = {2050-084X},
  doi       = {10.7554/eLife.02324},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119727},
  year      = {2014},
  abstract  = {We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.},
  language  = {en}
}
@article{CicovaDejungSkalickyetal.2016,
  author    = {Cicova, Zdenka and Dejung, Mario and Skalicky, Tomas and Eisenhuth, Nicole and Hanselmann, Steffen and Morriswood, Brooke and Figueiredo, Luisa M. and Butter, Falk and Janzen, Christian J.},
  title     = {Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  doi       = {10.1038/srep35826},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181021},
  year      = {2016},
  abstract  = {Trypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level, and in a systematic way. However, detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here, we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor Tb927.11.2400, identified previously in a SILAC-based comparative proteome study. Tb927.11.2400 shares 38\% amino acid identity with TbFlabarin (Tb927.11.2410), a procyclic form (PCF) stage-specific flagellar BAR domain protein. We named Tb927.11.2400 TbFlabarin-like (TbFlabarinL), and demonstrate that it originates from a gene duplication event, which occurred in the African trypanosomes. TbFlabarinL is not essential for the growth of the parasites under cell culture conditions and it is dispensable for developmental differentiation from BSF to the PCF in vitro. We generated TbFlabarinL-specific antibodies, and showed that it localizes in the flagellum. Co-immunoprecipitation experiments together with a biochemical cell fractionation suggest a dual association of TbFlabarinL with the flagellar membrane and the components of the paraflagellar rod.},
  language  = {en}
}
@article{GoosDejungJanzenetal.2017,
  author    = {Goos, Carina and Dejung, Mario and Janzen, Christian J. and Butter, Falk and Kramer, Susanne},
  title     = {The nuclear proteome of Trypanosoma brucei},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {7},
  doi       = {10.1371/journal.pone.0181884},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158572},
  pages     = {e0181884},
  year      = {2017},
  abstract  = {Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host. Here, we provide the nuclear proteome of procyclic Trypanosoma brucei, the stage that resides within the tsetse fly midgut. We have performed quantitative label-free mass spectrometry to score 764 significantly nuclear enriched proteins in comparison to whole cell lysates. A comparison with proteomes of several experimentally characterised nuclear and non-nuclear structures and pathways confirmed the high quality of the dataset: the proteome contains about 80\% of all nuclear proteins and less than 2\% false positives. Using motif enrichment, we found the amino acid sequence KRxR present in a large number of nuclear proteins. KRxR is a sub-motif of a classical eukaryotic monopartite nuclear localisation signal and could be responsible for nuclear localization of proteins in Kinetoplastida species. As a proof of principle, we have confirmed the nuclear localisation of six proteins with previously unknown localisation by expressing eYFP fusion proteins. While proteome data of several T. brucei organelles have been published, our nuclear proteome closes an important gap in knowledge to study trypanosome biology, in particular nuclear-related processes.},
  language  = {en}
}