JANZEN LAB

After establishing the foundations for current projects in our group with pioneer work on post-translational histone modifications and their influence on chromatin structure in African trypanosomes, we are now focussing on three different but complementary aspects of trypanosome biology. Currently, we are using this parasite as a model organism to unravel how cells are able to adapt to extremely different environments when they shuttle between different host organisms. Trypanosomes have to adapt their morphology, metabolism and energy sources during a complex life cycle in different hosts and changes in chromatin structure and nuclear architecture have been observed during this process. In a very fruitful collaboration with Dr. Falk Butter at the IMB in Mainz, we recently employed high-throughput proteomic techniques to understand how changes in chromatin structure are regulated during developmental differentiation.

Furthermore, we want to know how antigenic variation, a mechanism, which is essential for the parasite to evade the host’s immune response is regulated. Using biochemical approaches in combination with proteomic techniques , we identified several telomere-binding proteins that are involved in this process. We are now analysing the function of these proteins in detail.

Finally, we are interested how replication initiation is regulated in trypanosomes. Recently, we discovered that post-translational histone modifications mediated by DOT1 methyl transferases are necessary for replication initiation in trypanosomes. However, the exact mechanism behind this observation is still elusive. We are using biochemical and cell biology approaches to learn more about replication regulation in African trypanosomes.

The next challenge will be to transfer knowledge, techniques and expertise to answer similar questions in Leishmania parasites, which cause devastating diseases all over the world.

TelAP1 links telomere complexes with developmental expression site silencing in African trypanosomes (2018) Reis H, Schwebs M, Dietz S, Janzen CJ, Butter F. Nucleic Acids Res. Jan 29. doi: 10.1093/nar/gky028

The nuclear proteome of Trypanosome brucei (2017) Goos C, Dejung M, Janzen CJ, Butter F, Kramer S. PLoS One. Jul 20;12(7):e0181884. doi: 10.1371/journal.pone.0181884.

Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation (2016) Cicova Z, Dejung M, Skalicky T, Eisenhuth N, Hanselmann S, Morriswood B, Figueiredo LM, Butter F, Janzen CJ.
Sci Rep. Oct 25;6:35826. doi: 10.1038/srep35826.

Quantitative proteomics uncovers novel factors involved in developmental differentiation of Trypanosome brucei (2016) 
Dejung M, Subota I, Bucerius F, Dindar G, Freiwald A, Engstler M, Boshart M, Butter F & Janzen CJ

PLoS Pathogen 12(2): doi:10.1371/journal.ppat.1005439


Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes. (2014) Dindar G, Anger AM, Mehlhorn C, Hake SB, Janzen CJ.

Nat Commun. Nov 12;5:5313. doi: 10.1038/ncomms6313.


Comparative proteomics of two life cycle stages of stable isotope-labeled Trypanosoma brucei reveals novel components of the parasite's host adaptation machinery. (2013) Butter F, Bucerius F, Michel M, Cicova Z, Mann M, Janzen CJ.

Mol Cell Proteomics. Jan;12(1):172-9. doi: 10.1074/mcp.M112.019224.


DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei (2012)
Gassen A, Brechtefeld D, Schandry N, Arteaga-Salas JM, Israel L, Imhof A, Janzen CJ.

Nucleic Acids Res. Nov 1;40(20):10302-11. doi: 10.1093/nar/gks801