Universiteit Leiden

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Research project

Inflammafish: Cross-talk between inflammation and autophagy in tuberculosis

Effective host defence against tuberculosis bacteria depends on a properly balanced level of inflammation. The Inflammafish project uses zebrafish larvae to study how autophagy controls this inflammation and vice versa.

Duration
2016  -   2018
Contact
Annemarie Meijer
Funding
European Horizon-2020 Marie Curie Individual Fellowship - (H2020-MSCA-IF-2014 – GA 655424 - Inflammafish) European Horizon-2020 Marie Curie Individual Fellowship - (H2020-MSCA-IF-2014 – GA 655424 - Inflammafish)
Partners

Prof. Maria Leptin, EMBL Heidelberg

The increasing occurrence of multidrug-resistant Mycobacterium tuberculosis strains makes tuberculosis (TB) a key priority for infectious disease research. Inflammation and autophagy are two fundamental processes critical to TB pathogenesis. Accumulating evidence shows that TB disease is worsened by deregulation of the inflammatory response. On the other hand, autophagy has recently emerged as a crucial host defence mechanism. Autophagy counteracts the ability of mycobacteria to survive inside host cells and targets them for degradation. Autophagy is also thought to control the inflammatory response. However, the interaction between inflammation and autophagy in host defence against TB remains unclear.

Using a well-established zebrafish model of TB, we recently discovered that the DNA damage regulated autophagy modulator (DRAM1) protects against mycobacterial infection. This important autophagy regulator is also implicated in inflammation, as it strongly affects expression of the major pro-inflammatory cytokine, interleukin-1beta (IL1B).  In the Inflammafish project, Marie Curie fellow Dr. Monica Varela will use the zebrafish TB model to investigate how IL1B signalling and DRAM1 or other autophagy mediators reciprocally influence each other’s activities. The central hypothesis is that a proper balance between these activities is decisive for effective host defence against TB. The project may provide new insights into regulatory pathways that could potentially be intervened in treatment of TB or other inflammatory diseases with common characteristics.

Connection with other research

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