SPP 1580:  Intracellular Compartments as Places of Pathogen-Host Interaction

• Subject Area: Medicine ; Biology
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 173096411

More than 100 years have passed since microorganisms were identified as causes of infectious diseases. Yet, we are still far from being able to prevent all infections diseases such as malaria or tuberculosis or to even treat all of them efficiently. Many infectious microorganisms share the property that they have to enter a host cell to multiply. Often even phagocytic cells of the immune system are infected, which normally serve the defence against microbial invaders. The pathogens reprogramme them for their own benefit. The microorganism then exists in membrane-enclosed spaces within the host cell, so-called cell compartments. Research into these compartments as places of decision between microbial multiplication and elimination is at the heart of this Priority Programme. Central questions to be addressed are: How are the pathogen-containing compartments composed and which physiological conditions are present within them? Which pathogen-produced and which host-produced substances are responsible for the establishment and maintenance of these compartments? Which substances of the pathogen or the host are transported in which way out of the compartment or into it? Which interactions exist between the pathogen compartment and other compartments of the infected cell? How is it determined, which host cell vesicles interact with which pathogen-containing compartment and which do not? How do pathogens eliminate intra-compartmental defence mechanisms of the host? Germany has an excellent and traditionally biochemically oriented microbiology. Over the years, a strong cell biology was established at its side, which combined molecular biology with the latest imaging techniques in order to understand cellular processes. This Priority Programme will doubtlessly have a lasting impact on research in this field and it will allow to be internationally competitive.

• DFG Programme: Priority Programmes
• International Connection: Norway, Switzerland, United Kingdom

Projects

• Analysis of the function and regulation of Rab20 during mycobacterial phagosome maturation (Applicant Gutierrez, Maximiliano )
• Biogenesis of novel membrane compartments in Salmonella enterica-infected host cells (Applicant Hensel, Michael )
• Characterisation of the vacuolar compartment of malaria parasites within human red blood cells (Applicant Spielmann, Tobias )
• Characterizing Plasmodium proteins at the host-pathogen vacuolar interface during parasite development in the liver (Applicant Ingmundson, Alyssa )
• Chlamydia interacts with the Golgi apparatus - understanding the underlying molecular mechanisms (Applicant Heuer, Dagmar )
• Clade specific virulence patterns of M. tuberculosis complex strains in human macrophages: Molecular mechanisms underlying phagosomal escape and induction of cell death. (Applicants Reiling, Norbert ;  Schütze, Stefan )
• Establishment and maintenance of the chlamydial inclusion: requirement for septins and the inhibition of host cell translation (Applicant Häcker, Georg )
• Exported chaperones/co-chaperones of P. falciparum: Interaction with host proteins, and relevance for intra-erythrocytic survival of the parasite (Applicant Przyborski, Jude Marek )
• Functional analysis of molecular components of the habitat of Leishmania spp. - the protozoan parasites causing human leishmaniases (Applicant Aebischer, Anton )
• Functional characterization of cell-specific differences of L. major-containing phagolysosomes in macrophages and dendritic cells (Applicants von Stebut-Borschitz, Ruth Esther ;  Tenzer, Stefan )
• Functional phosphoinositide lipidomics of Legionella-containing vacuoles (Applicant Hilbi, Hubert )
• IFN-dependent macrophage-intrinsic innate resistance to Legionella pneumophila (Applicant Opitz, Bastian )
• Impact of the cytoprotective chaperone HSP25/27 on the structural integrity and autophagic degradation of chlamydial compartments (Applicant Knittler, Michael R. )
• In vivo Formation and Maintenance of Salmonella-Containing Vacuoles (SCVs) in Enterocytes using a Novel Neonatal Mouse Model (Applicant Hornef, Mathias Walter )
• Investigation of Francisella virulence and host cell defense mechanisms in Dictyostelium (Applicant Hagedorn, Monica )
• Leishmania major promastigote entry of the of the autophagic compartment and amastigote escape from the parasitophorous vacuole (Applicants Walther, Paul ;  van Zandbergen, Ger )
• Lysosomal Membrane Proteins and their Roles in Phagosome Maturation (Applicants Haas, Albert ;  Saftig, Paul )
• Malaria intrahepatic interactions and trafficking: Deciphering the molecular machinery driving vesicular trafficking and membrane fusion between the hepatic host environment and malarial parasite for parasitophorous vacular membrane dynamics (Applicant Müller, Ann-Kristin )
• Mechanisms underlying parasite induced permeability changes of the human erythrocyte membrane - how much is host, how much is parasite? (Applicant Przyborski, Jude Marek )
• Priority Programme 1580: Administration, Workshops, Exchange Programme and Conferences (Applicant Haas, Albert )
• Protein networks involved in biogenesis of the Salmonella proliferative niche (Applicant Dikic, Ivan )
• Significance of Legionella pneumophila phospholipases for modification of lipids within the phagosomal membrane (Applicant Flieger, Antje )
• Simkania negevensis containing vacuoles: Formation, trafficking and subversion of host signaling (Applicant Rudel, Thomas )
• Solute provision to the chlamydial inclusion (Applicant Haferkamp, Ilka )
• State of the art ultrastructural analysis of pathogen-containing compartments (Applicant Griffiths, Ph.D., Gareth )
• Structural and biophysical characterization of the interaction between intracellular pathogens and phagosome membranes (Applicants Gutsmann, Thomas ;  Lindner, Buko )
• Survival and proliferation of human pathogenic Candida species within phagocytes (Applicant Hube, Bernhard )
• The egress of malaria gametocytes from the red blood cell following parasite transmission to the mosquito (Applicant Pradel, Gabriele )
• The phagosomal fate of Mycobacterium tuberculosis-infected dying/dead cells (Applicant Schaible, Ulrich E. )
• The role of the human guanylate-binding protein 1 in the formation and trafficking of phagosomes and other pathogen containing membrane compartments (Applicant Praefcke, Gerrit )
• Trafficking of the Coxiella burnetii-containing vacuole (Applicant Lührmann, Anja )

• Spokesperson: Professor Dr. Albert Haas