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 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 FLI in Greifswald, we employ high-throughput proteomic techniques to understand how  chromatin remodelling and other essential cellular processes are regulated during developmental differentiation.

Furthermore, 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 current challenge in our laboratory is the transfer of knowledge, techniques and expertise to answer similar questions in Leishmania parasites, which cause devastating diseases all over the world. We recently performed a large quantitative proteomics analysis of macrophages infected with different Leishmania parasites to investigate how protein profiles change during the course of the infection. The aim of this study is to identify parasite factors that are essential to establish chronic infections in vertebrate hosts.

The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana (2025) Eisenhuth N, Rauh ET, Mitnacht M, Debus A, Schleicher U, Butter F, Pruzinova K, Volf P, Janzen CJ. Front Cell Infect Microbiol. Jan 20;14:1502339. doi:10.3389/fcimb.2024.1502339.

A novel SNF2 ATPase complex in Trypanosoma brucei with a role in H2A.Z-mediated chromatin remodelling (2022) Vellmer T, Hartleb L, Fradera Sola A, Kramer S, Meyer-Natus E, Butter F, Janzen C PLoS Pathog. Jun 8;18(6):e1010514. doi: 10.1371/journal.ppat.1010514

A DOT1B/Ribonuclease H2 Protein Complex Is Involved in R-Loop Processing, Genomic Integrity, and Antigenic Variation in Trypanosoma brucei (2021) Eisenhuth N, Vellmer T, Rauh E, Butter F, Janzen C mBio Dec 21;12(6):e0135221. doi: 10.1128/mBio.01352-21

Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei (2020)  Doleželová E, Kunzová M, Dejung M, Levin M, Panicucci B, Regnault C, Janzen CJ, Barrett MP, Butter F, Zíková A.PLoS Biol. Jun 10;18(6):e3000741. doi: 10.1371/journal.pbio.3000741. 

Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation (2020) Leal AZ, Schwebs M, Briggs E, Weisert N, Reis H, Lemgruber L, Luko K, Wilkes J, Butter F, McCulloch R, Janzen C Nucleic Acids Res.  Sep 25;48(17):9660-9680. doi: 10.1093/nar/gkaa686

Genome organization and DNA accessibility control antigenic variation in trypanosomes (2019) Müller L, Cosentino R, Förstner K, Guizetti J, Wedel C, Kaplan N, Janzen C, Arampatzi P, Vogel J, Steinbiss S, Otto D, Saliba A, Sebra R, Siegel N Nature Nov;563(7729):121-125.  

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.

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