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Sie sind hier: Startseite Funded Projects Monica Hagedorn (2014-2017)

Monica Hagedorn (2014-2017)

Investigation of Francisella virulence and host cell defense mechanisms in Dictyostelium

The genus Francisella comprises intracellular pathogens that can cause potentially fatal infections in humans (tularaemia caused by F. tularensis) and major economic losses, e.g. F. noatunensis in aquaculture. Because of the high virulence of F. tularensis and the lack of suitable model organisms, their infection of phagocytic immune cells is not well understood.

In the proposed project we want to establish the amoeba Dictyostelium as a host system to study Francisella virulence and cellular host defense mechanisms. Our preliminary experiments indicate that Dictyostelium is efficiently infected by F. noatunensis, a natural fish pathogen and genetically close to F. tularensis. The use of molecular, cell biological and microscopical approaches will allow us to dissect the pathway which leads to establishment and maintenance of infection. Furthermore, with the help of Francisella knock-out mutants we will be able to investigate the role of conserved virulence loci in infection (e.g. iglC).

The new model system will allow the dissection of interactions between the phagocytic host cell and pathogenic Francisella in a genetically tractable system. It is a long-term goal to use this system for screening approaches that allow either the identification of host pathways, Francisella virulence factors or chemical compounds affecting Francisella growth in phagocytes.

 

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