Charakterisierung von Signaltransduktionsnetzwerken in der Membran von Latex-bead- und Mykobakterien-haltigen Phagosomen

• Applicant: Privatdozent Dr. Mark Kühnel
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2002 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5364265

Mycobacteria are important intracellular pathogens, these bacteria are able to survive in the phagosomes or macrophages. The processes that allow these bacteria to persist and survive inside the macrophage are identified, but poorly understood. This proposal deals with the in vitro analysis of pathogenic M. avium- (and M. tuberculosis-) and the non-pathogenic M. smegmatis-containing phagosomes, and, as a reference, the latex bead phagosomes (LBP) from mouse macrophages in order to understand more about the signalling networks in the membrane, of this organelle, and find new therapeutical treatments against these organisms. There are five different experimental goals. These include analysis of: 1) The components involved in the nucleation of actin on mycobacteria-containing phagosomes in vitro and identification of effector molecules that regulate actin nicleation. 2) The lipid composition of the phagosomal membrane of mycobacteria-containing phagosomes by TLC, HPLC, and mass-spectrometry. 3) The signalling networks of mycobacteria containing phagosomes by bioinformatical methods. 4) The effects of substances found to activate actin nucleation on live M. avium phagosomes in vitro for their effects on infected cells. This provides a system for predicting effectors that increase the phagosomal killing process. 5) A second phagosomal process, acidification, will be studied in the third year.

• DFG Programme: Research Grants