Regulation of the NLRP3 Inflammasome by a Novel Mechanism

1:00pm - 2:00pm / Monday 25th February 2019 / Venue: Lecture Theatre 1 Life Sciences Building
Type: Seminar / Category: Research / Series: GSTT Seminar Series
  • Suitable for: Staff and students with an interest in Genomes, Systems and Therapeutic Targeting
  • Admission: Free
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Speaker: Sambit Nanda (Dundee University)

Malfunctioning of inflammasomes is associated with serious human diseases. Mutations in NLRP3 and MEFV (also known as Pyrin) are linked to auto-inflammatory and fever syndromes. Aberrant activation of the NLRP3 inflammasome has also been implicated in atherosclerosis, type II diabetes, inflammatory bowel diseases, and neurodegenerative diseases. The activation of the NLRP3 inflammasome requires two signals, namely a PAMP (Pathogen-Associated Molecular Pattern) such as ligands that activate Toll-Like Receptors (TLRs) and, a second signal, which in majority of the cases is a DAMP (Damage-Associated Molecular Pattern). The two signals together trigger the formation of an inflammasome, a multi-protein complex comprising the proteins NLRP3, ASC and Caspase 1. This leads to the activation of Caspase 1, which cleaves pro-IL-1 and pro-IL-18 to their mature secreted forms.

Using proteomic, genetic and biochemical approaches, I have identified a novel mechanism that may explain how TLR signaling regulates the formation of the NLRP3 inflammasome complex and Caspase-1 activation. In the seminar, I will reveal the identity of protein(s) and present a hypothesis for their critical role in activating the NLRP3 inflammasome.