Interrogating NLRP3 inflammasome activation mechanisms

Inflammasomes are intracellular sensors of pathogens and danger signals. The NLRP3 inflammasome is involved in host defence against cancer and infection, but is also a major instigator of pathological inflammation in several diseases. Understanding its elusive mechanism of activation is one of the biggest open questions in the field of immunology and is a crucial step towards its therapeutic targeting of NLRP3. Using different approaches, both groups involved in this project have individually made substantial contributions towards this goal and each received prestigious ERC funding related to inflammasome research (StG and PoC grants to Groß and CoG funding to Ricci). Here, we propose to take first steps towards joining forces between our groups in Freiburg and Strasbourg and combine our complementary expertise and unique methods to specifically tackle the problem of NLPR3 activation mechanism. Novel pharmacologic NLRP3 activators developed in Freiburg will be jointly investigated in Strasbourg to elucidate their mode of action including their impact on intracellular NLRP3 trafficking. We anticipate that the Seed Money project will deliver key new insight into the activation of NLRP3, will establish a sustainable collaboration between our groups that could lead to new joint projects and funding applications, and will increase the international visibility of the European Campus partners in the inflammasome field.