Direkt zum Inhalt | Direkt zur Navigation

Benutzerspezifische Werkzeuge

Sektionen
Project 1
Sie sind hier: Startseite / Individual Projects / Project 1

Project 1

Ludwig Eichinger, Angelika Anna Noegel

The professional phagocyte Dictyostelium as a host model for pathogens

Institute for Biochemistry, University of Cologne

Publications

Brief description in German:
Organismen verfügen über viele Mechanismen, um Pathogene abzuwehren und zu bekämpfen, dazu gehört die Aufnahme in Fresszellen durch Phagozytose und der folgende Erregerabbau. Wir untersuchen Phagozytose und Infektion in Dictyostelium discoideum, einem professionellen Phagozyten, der sich in den letzten Jahren auch als geeigneter Wirt für eine Reihe klinisch relevanter pathogener Mikroorganismen erwiesen hat. Wir werden in diesem Projekt sowohl die Rolle des Aktinzytoskeletts in der Phagozytose von Partikeln als auch von Makroautophagie in der Etablierung und Eliminierung von Pathogenen untersuchen.

Summary
The defense against pathogens is of central importance for the survival of organisms. It relies on the ability of cells to recognize and respond appropriately to the invader. In mammals, a first line of defense is phagocytosis and subsequent degradation of invaders by cells of the innate immune system.

The professional phagocyte Dictyostelium discoideum can be infected with clinically relevant bacterial pathogens and has contributed as a model organism to the elucidation of important pathogen/host cell interactions. On the host side, remodeling of the actin cytoskeleton and macroautophagy (hereafter autophagy) are focus of our work aiming at unraveling the functions of and the connection(s) between these two fundamental cellular systems in the cell-autonomous defense against bacterial infection.

In recent years autophagy was identified as an important cellular defense mechanism against pathogens. It also turned out that a number of pathogens are able to subvert this cellular defense. However, the molecular details of the complex interplay between host and pathogen in these processes are far from being understood.

We will characterize in part A of the project the role of autophagy, namely of the core autophagy proteins ATG8 (LC3), ATG9 and ATG16, in phagocytosis and infection. In particular, we will focus on the dynamics of these proteins during uptake and elimination of bacteria, on the nature of the molecular link(s) between phagocytosis and autophagy and on the search for ATG16 interaction partners.

These studies will lead to the identification of new proteins that are involved in bacterial uptake and link autophagy and phagocytosis. In the future these proteins could constitute promising new targets in the fight against bacterial infections.

In part B of the project, we will analyse the function and regulation of D. discoideum and mammalian coronin 7 in phagocytosis and infection. In particular we will study the impact of coronin 7 on the actin cytoskeleton and its role in phagocytosis and the possible link between coronin 7 and autophagy. The actin cytoskeleton is important for phagosome formation, vesicle generation, transport and fusion. Crucial for its involvement is the property to assemble and disassemble rapidly.

Based on our results with the single small coronin in D. discoideum, we will investigate the possible regulation of coronin 7 in D. discoideum and mammals by Rho GTPases and downstream signalling proteins in the innate immune response. The mammalian coronin 7 is highly expressed in macrophages.

Furthermore, a coronin 7 knock-out mouse model has been established for in vivo experiments. These studies will reveal whether this protein has a similar role in mammals and Dictyostelium.

List of publications resulting from the project
Peer-reviewed publications:

Deckstein, J., J. van Appeldorn, M. Tsangarides, K. Yiannakou, R. Müller, M. Stumpf, S.K. Sukumaran, L. Eichinger, A.A. Noegel, and T.Y. Riyahi. 2015. The Dictyostelium discoideum GPHR Ortholog Is an Endoplasmic Reticulum and Golgi Protein with Roles during Development. Euk Cell 14:41-54.

Xiong, Q., C. Ünal, J. Matthias, M. Steinert, and L. Eichinger. 2015. The phenotypes of ATG9, ATG16 and ATG9/16 knock-out mutants imply autophagy-dependent and -independent functions. Open Biol. 5(4), 150008.

Swaminathan, K., M. Stumpf, R. Müller, A-C. Horn, J. Schmidbauer, L. Eichinger, A. Müller-Taubenberger, J. Faix, and A.A. Noegel. 2015. Coronin7 regulates WASP and SCAR through CRIB mediated interaction with Rac proteins. Sci. Rep. 5, 14437.

 

Omosigho N.N., K. Swaminathan, M. Plomann, A. Müller-Taubenberger, A.A. Noegel, and T.Y. Riyahi. 2014. The Dictyostelium discoideum RACK1 orthologue has roles in growth and development. Cell Commun Signal. 12, 37. doi/10.1186/1478-811X-12-37.

Swaminathan K, A. Müller-Taubenberger, J. Faix, F. Rivero, and A.A. Noegel. 2014. A CRIB domain mediates functions of coronin. Proc. Natl. Acad. Sci. USA 111, E25-33. doi/10.1073/pnas.1315368111.

Glöckner, G., N. Hülsmann, M. Schleicher, A.A. Noegel, L. Eichinger, C. Gallinger, J. Pawlowski, R. Sierra, U. Euteneuer, L. Pillet, A. Moustafa, M. Platzer, M. Groth, K. Szafranski, and M. Schliwa. 2014. The Genome of the Foraminiferan Reticulomyxa filosa. Curr. Biol., 24, 11–18. doi/10.1016/j.cub.2013.11.027.

Riyahi T.Y., F. Frese, M. Steinert, N.N. Omosigho, G. Glöckner, L. Eichinger, B. Orabi, R.S.B. Williams, and A.A. Noegel. 2011. RpkA, a highly conserved GPCR with a lipid kinase domain, has a role in phagocytosis and anti-bacterial defense. PLoS ONE, 11, e27311.

Sillo A., J. Matthias, R. Konertz, S. Bozzaro, and L. Eichinger. 2011. Salmonella thyphimurium is pathogenic for Dictyostelium cells and subverts the starvation response. Cell. Microbiol., 13, 1793–1811.

Heidel, A.J., H.M. Lawal, M. Felder, C. Schilde, N.R. Helps, B. Tunggal, F. Rivero, U. John, M. Schleicher, L. Eichinger, M. Platzer, A.A. Noegel, P. Schaap, and G. Glöckner. 2011. Phylogeny-wide analysis of social amoeba genomes highlights ancient origins for complex intercellular communication. Genome Res. 21, 1882-1891.

Shina, M.C., A. Müller-Taubenberger, C. Ünal, M. Schleicher, M. Steinert, L. Eichinger, R Müller, G. Glöckner, and A.A. Noegel. 2011. Redundant and unique roles of coronin proteins in Dictyostelium. Cell. Mol. Life Sci., 68, 303–313.

Reviews

Müller-Taubenberger, A., A. Kortholt, and L. Eichinger. 2013. Simple System - Substantial Share: The use of Dictyostelium in cell biology and molecular medicine. Eur. J. Cell Biol., 92, 45-53. doi/10.1016/j.ejcb.2012.10.003.

Bozzaro, S. and L. Eichinger. 2011. The professional phagocyte Dictyostelium discoideum as a model host for bacterial pathogens. Curr. Drug Targets, 12, 942-954.

Eichinger, L. 2011. Model organisms to study host - pathogen interaction: prerequisites for the identification of novel drug targets. Curr. Drug Targets, 12, 934-935.

Non peer-reviewed publications:

Bozzaro, S., B. Peracino, and L. Eichinger. 2013. Dictyostelium host response to Legionella infection: strategies and assays. Methods Mol. Biol., 954, 417-438. doi: 10.1007/978-1-62703-161-5_26.

back to top