Lehrstuhl für Zell- und Entwicklungsbiologie

JANZEN LAB

We investigate how African trypanosomes and Leishmania parasites adapt to different host environments

Research synopsis

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 lear 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.

Recent publications

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

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

Quantitative proteomics uncovers novel factors involved in developmental differentiation of Trypanosoma brucei.

Dejung M, Subota I, Bucerius F, Dindar G, Freiwald A, Engstler M, Boshart M, Butter F & Janzen CJ

PLoS Pathogen 2016 12(2): doi:10.1371/journal.ppat.1005439


Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes.

Dindar G, Anger AM, Mehlhorn C, Hake SB, Janzen CJ.

Nat Commun. 2014 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.

Butter F, Bucerius F, Michel M, Cicova Z, Mann M, Janzen CJ.

Mol Cell Proteomics. 2013 Jan;12(1):172-9. doi: 10.1074/mcp.M112.019224.


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

Nucleic Acids Res. 2012 Nov 1;40(20):10302-11. doi: 10.1093/nar/gks801


Epigenetic regulation in African trypanosomes: a new kid on the block.

Figueiredo LM, Cross GA, Janzen CJ.

Nat Rev Microbiol. 2009 Jul;7(7):504-13. doi: 10.1038/nrmicro2149.

RESEARCH TOPICS

Telomere structure & function

Telomeres are probably one of the most investigated chromatin structures in eukaryotes. We are interested how telomere-binding complexes influence antigenic variation, chromosome integrity and recombination events

Chromatin structure

We want to learn why changes in chromatin structure and nuclear architecture is important for developmental differentiation in trypanosomes.

Replication regulation

322Histone modifications regulate replication initiation in trypanosomes. We try to unravel the exact molecular machinery behind this mechanism

Kontakt

Lehrstuhl für Zoologie I - Zell- und Entwicklungsbiologie
Am Hubland
97074 Würzburg

Tel.: +49 931 31-84250
Fax: +49 931 31-84252
E-Mail

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Hubland Süd, Geb. B1 Hubland Nord, Geb. 32 Julius-von-Sachs-Platz 2 Fabrikschleichach Hubland Süd, Geb. B2 Campus Medizin