LMU, Division of Genetics
Großhaderner Straße 2
+49 (89) 2180 - 74600
Fax: +49 (89) 2180 - 74629
We are interested in signaling mechanisms involved in parasitic life cycle development and in the host-parasite interaction of global pathogens. Trypanosomes and Leishmania cause severe tropical diseases including sleeping sickness, Chagas disease or Kala-Azar in man and are transmitted by blood-feeding insects. Host body temperature change is a key signal that induces differentiation of trypanosomes when they adapt to the environment of the insect vector. We identified a protein kinase related to cAMP-dependent protein kinases that is however regulated by temperature and nucleosides but not by cAMP. The structural investigation of this unconventional kinase gives us insights into an exotic signaling protein and its evolution and has revealed a potential drug target candidate that is currently followed up in a translational drug development project. Another project studies the adenylate cyclase surface receptor family that is involved in subversion of the mammalian host´s innate immunity and in swarming motility and development in the insect vector. A third project connects the signaling systems with the highly flexible metabolic regulation and adaptation that is essential for the infection process.
Bachmaier, S., Volpato Santos, Y., Kramer, S., Githure, G.B., Klockner, T., Pepperl, J., Baums, C., Schenk, R., Schwede, F., Genieser, H.G., et al. (2019). Nucleoside analogue activators of cyclic AMP-independent protein kinase A of Trypanosoma. Nat Commun 10, 1421.
Dejung, M., Subota, I., Bucerius, F., Dindar, G., Freiwald, A., Engstler, M., Boshart, M., Butter, F., and Janzen, C.J. (2016). Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei. PLoS Pathog 12, e1005439.
Bachmaier, S., Witztum, R., Tsigankov, P., Koren, R., Boshart, M., and Zilberstein, D. (2015). Protein kinase A signaling during bidirectional axenic differentiation in Leishmania. Int J Parasitol 46, 75-82.
Gould, M.K., Bachmaier, S., Ali, J.A.M., Alsford, S., Tagoe, D.N.A., Munday, J.C., Schnaufer, A.C., Horn, D., Boshart, M., and de Koning, H.P. (2013). Cyclic AMP Effectors in African Trypanosomes Revealed by Genome-Scale RNA Interference Library Screening for Resistance to the Phosphodiesterase Inhibitor CpdA. Antimicrob Agents Chemother 57, 4882-4893.
Salmon, D., Vanwalleghem, G., Morias, Y., Denoeud, J., Krumbholz, C., Lhomme, F., Bachmaier, S., Kador, M., Gossmann, J., Dias, F.B.S., et al. (2012). Adenylate Cyclases of Trypanosoma brucei Inhibit the Innate Immune Response of the Host. Science 337, 463-466.
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. Mol Microbiol 84, 225-242.
Primary Technique(s): reverse genetics (gene knock-out/knock-in, RNAi, inducible gene expression, etc.) in parasites, biochemistry and structural biology of protein kinases, phospho-proteomics, cell biology, and fluorescence imaging, in vitro culture models of parasite differentiation.
Model Organisms: Trypanosoma and Leishmania (protozoans)