Inflammasome Biology

A number of cytosolic receptors of the Nod-like receptor (NLR) and PYHIN protein families can assemble large cytoplasmic multi-protein complexes together with the protein apoptosis related speck like protein (ASC). These signaling platforms, termed 'inflammasomes', activate the inflammatory caspase-1 which cleaves and activates members of the pro-inflammatory interleukin-1b cytokines. Activated caspase-1 can further initiate cell death and the release of a multitude of intracellular molecules. 

We are particularly interested in the NLRP3 and AIM2 inflammasomes. AIM2 inflammasomes form in response to cytosolic double stranded DNA and the NLRP3 inflammasome is activated by a broad number of stimuli, including bacterial toxins, crystals and endogenous danger signals. The activation mechanisms leading to NLRP3 inflammasome formation are not understood in detail.

We aim to identify:

  • the mechanisms by which the NLRP3 inflammasome is triggered
  • the difference in NLRP3 inflammasome activation in response to different stimuli
  • which factors regulate the NLRP3 inflammasome activation
  • the compounds that interfere with inflammasome activation