Intracellular Compartments as Places of Pathogen - Host Interaction
The problem and the question
Normally, bacteria cannot enter cells of our body let alone multiply within them. Intracellular’ pathogenic microorganisms (bacteria, protozoa, fungi) are an exception. These microorganisms can enter cells of ‘host’ organisms and multiply within them. Prominent pathogens of this group are Mycobacterium tuberculosis (causing tuberculosis), Salmonella enterica (severe food poisoning) or Plasmodium falciparum (malaria). The infected host cells are often part of the host defence system whose duty would be to eliminate the microbial intruder. Yet, these host cells are re-programmed by the pathogens, turning them into hospitable homes and allowing pathogens to exist and multiply in defined membrane-surrounded locations, the subcellular compartments. Research into these compartments as locations of the decision between multiplication and elimination of a microbial pathogen is the core of this Programme. Particularly relevant questions are:
• Which are the constituents of pathogen-containing compartments?
• Which (patho-) physiological conditions are found in these compartments?
• Which pathogen- and host-derived compounds contribute to the establishment and the maintenance and disruption of these compartments?
• Which interactions and vesicular trafficking events occur between the pathogen-containing compartment and other compartments of the infected cell and how are these interactions regulated?
These and and other questions are addressed in this Programme using a large variety of pathogens, model particles and host cells. Pathogens include the yeast Candida glabrata (systemic infections of humans), the protists Leishmania (human cutaneous leishmaniosis) and Plasmodium falciparum (malaria), and the bacteria Legionella pneumophila (legionnaires‘ disease), Salmonella enterica (salmonellosis, food poisoning) and several others. Host cells investigated include human neutrophils, mouse macrophages, the amoeba Dictyostelium and others. A central electron microscopy platform supplies the know-how and equipment for sophisticated ultrastructural analysis, high-end mass spectrometry is used in other projects
This Programme was installed by the Senate of the Deutsche Forschungsgemeinschaft (Bonn, www.dfg.de). Following announcement of the Programme and the invitation to apply for grants within SPP1580, the positively evaluated 24 projects started in 2011. The second round of calls and evaluations took place in 2013/14 and since July 2014, the Programme is in its second funding period. This Programme gives laboratories from all over Germany (and one Norwegian group) the opportunity to cooperate on the above questions. Laboratories with a more cell biological experience cooperate with those being more microbiological, lipid biophysicists with electron microscopists and labs with different models cooperate to test findings from one experimental system in the other.
Several meetings of SPP members only and with scientists from beyond the Programme take place in each funding period. Additionally, this Programme allows young scientists funded by the Programme to visit training courses especially set up for them, such as workshops on related topics and meeting opportunities are given. Also, gender equality measures specifically support female scientists, e.g., with special seminars and networking activities.
From 2014-2017, this Programme is in its second (and automatically last) funding period. It is therefore not possible to become a new member.
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Photo above: Scanning electron micrograph of a murine J774E macrophage colonising a glass splinter and, at the same time, reaching out for bacteria (green) in an attempt to phagocytose them. Photo from U. Strübing and C. Schüller from the lab of Prof. Haas. Cover page from the journal Traffic, Wiley Press, April 2007