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Référence
IGBMC/POST-DOC R. RICCI
Type de contrat
POST-DOC
Date de publication
20/07/2023
The inflammasome is an intracellular multiprotein complex that senses sterile tissue damage
and infectious agents to initiate innate immune responses. Distinct inflammasomes
containing specific sensing molecules exist. The NLRP3 inflammasome is unique as it detects a broad range of cellular stress signals but a primary and converging sensing mechanism initiating inflammasome assembly remains ill-defined. We found that NLRP3 binds altered endomembranes because of disruption of inter-organelle contact sites in response to danger signals. However, little is known about this fundamentally new mechanism of pattern recognition linking organelle spatial organization and innate immunity. The organellegenerated signals sensed by NLRP3 and the mechanisms underlying membrane recruitment and activation of the inflammasome remain largely unexplored and thus will be subject of this proposal. The major limit hampering their identification is the difficulty to disentangle the complex cell response to the variety of stimuli leading to NLRP3 activation. We aim to push this limit through an unprecedented combination of approaches ranging from in vitro reconstitution studies with isolated organelles and artificial liposomes and proteo-lipidomics, to cryo-FIB and cryo-ET imaging, molecular modelling, and in vivo testing of the physiological relevance of in vitro findings. This project will lay the foundation for how altered
endomembranes serve as danger-associated molecular patterns to trigger innate immune
responses.
Modalités de candidature
Applications including cover letter, detailed CV, copies of certificates, and contact information
of two referees, should be sent latest 30th of September 2023 as a single pdf file (no more
than 10 MB) via email to: ricci@igbmc.fr.
Associé à :
- Équipe(s) : La signalisation cellulaire de stress dans le métabolisme et l'inflammation
