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Prof. Dr. Michael Boshart

Head of Protozoan Genetics

Affiliation

LMU, Division of Genetics

Contact

Ludwig-Maximilians-University Munich
Biozentrum Martinsried
Großhaderner Straße 2
D-82152 Martinsried

Phone: +49 (89) 2180 - 74600
Fax: +49 (89) 2180 - 74629

Website: http://www.genetik.biologie.uni-muenchen.de/people/team_boshart/boshart/index.html

Research Focus

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 sigaling by cAMP and the signaling cascade that transmits the temperature, and aim at identification of  the primary thermosensor. We also investigate wether this thermosensing mechanism is conserved in related organisms like leishmania, another important pathogen. Insights into exotic signaling systems and their evolution is also expected to reveal potential drug target candidates for therapy of neglected tropical diseases.

References:

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)