LMU, Division of Genetics
Großhaderner Straße 2
+49 (89) 2180 - 74600
Fax: +49 (89) 2180 - 74629
The group uses protozoan Trypanosoma as a model system to study signaling mechanisms in parasitic life cycle development and in the host-parasite interaction as well as the evolution of signaling pathways in general. Trypanosomes cause severe tropical diseases including sleeping sickness in man and are transmitted by a blood feeding insect. Our recent findings include: (1) Surface signaling proteins (adenylate cyclases) of the parasite are activated upon the attack of immune cells and the cAMP produced silences these cells. This allows the parasites to subvert the innate immunity of the host and to establish infection. (2) Host body temperature change is a key signal that induces differentiation of these parasites when they adapt to the environment of the insect vector. A protein kinase related to cAMP-dependent protein kinases that is regulated by temperature and regulates this differentiation. We investigate unconventional sigaling by cAMP in trypanosomes and the PKA-related kinases at the structural and biochemical level. Insights into exotic signaling systems and their evolution is also expected to reveal potential drug target candidates for therapy of neglected tropical diseases. (3) The metabolism of these parasites is highly flexible and metabolic adaptation is essential for the infection process. More recently we focus on the link between metabolic sensing and these adaptations.
Engstler M. and Boshart M. (2004) Cold shock and regulation of surface protein trafficking convey sensitization to inducers of stage differentiation in Trypanosoma brucei. Genes Dev 18: 2798–2811
Engstler, M., Pfohl, T., Herminghaus, S., Boshart, M., Wiegertjes, G., Heddergott, N. and Overath, P. (2007). Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell: 131, 505-515
Salmon, D., Bachmaier, S., Krumbholz, C., Kador, M., Gossmann, J.A., Uzureau, P., Pays, E. and Boshart, M. (2012). Cytokinesis of Trypanosoma brucei bloodstream forms depends on expression of adenylyl cyclases of the ESAG4 or ESAG4-like subfamily. Molecular Microbiology 84: 225-242
Salmon, D., Vanwalleghem, G., Morias, Y., Denoeud, J., Krumbholz, C., Lhomme, F., Bachmaier, S., Kador, M., Gossmann, J., Dias, F.B., et al. (2012). Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host. Science in press DOI: 10.1126/science.1222753
Primary Technique(s): reverse genetics (gene knock out/knock in, RNAi, inducible gene expression etc.), 3rd generation DNA cloning, biochemistry of protein kinases, gene expresssion analysis, fluorencence imaging, protein expression (E. coli, Baculovirus, L. taretolae), in vitro culture models of parasite differentiation. In collaboration: phosphoproteomics, metabolomics, protein crystallization, parasite passage in Tsetse flies.
Model Organisms: Trypanosoma and Leishmania (protozoans)