#CTGCT Science Talks are back!

This time we have a talk open to everyone by dr. Iva Hafner Bratkovič from the Department of Synthetic Biology and Immunology at the @kemijski.bsky.social.
Her talk is titled "Inflammasome-inspired cancer immunotherapy"

Join us! forms.office.com/e/KJTTsMyETk
#Webinar

Thank you!

#LocationLocationLocation! Cool study about #Inflammasome @ivahb.bsky.social @elvirab.bsky.social &co, many congrats to the team! doi.org/10.1038/s414...

NLRP3 inflammasomes can assemble on most organelles. A beautiful study by Hafner et al demonstrate the flexibility of organelles that can support inflammasome activation. Kudos to the authors on an intriguing study.
www.nature.com/articles/s41...
@ivahb.bsky.social @elvirab.bsky.social

Are there spatial restrictions in NLRP3 #inflammasome activation? I am super excited to share our new study spearheaded by amazing @elvirab.bsky.social
www.nature.com/articles/s41...

Huge thanks to our incredible team of Pyrocellfluencers
@kemijski.bsky.social and collaborators: Taja Železnik Ramuta, Sara Orehek, Mateja Erdani Kreft, Matthias Geyer, Roman Jerala and @ivahb.bsky.social. 🔥💪

Subcellular location of NLRP3 is not essential, but clustering on different scaffolds is. This explains how NLRP3 can react to so many diverse stress signals.
9/9

Surprisingly, this activation could not be blocked by MCC950, suggesting that clustering of NLRP3 induces rearrangements of inactive NLRP3 leading to active NACHT-based oligomer formation.
8/9

To test if lipid membranes are truly dispensable, we fused NLRP3 to TDP43, a protein that forms cytosolic condensates. That alone was enough to trigger inflammasome assembly without any external stimulus.
7/9

We showed that NLRP3 can be activated from different types of scaffolds not just membranes. Variants targeted to the Golgi (GOLGB1) or centrosome (PACT) triggered IL-1β release after priming alone. Both formed multiple spots in the cell, resembling activated NLRP3.
6/9

The polybasic segment in NLRP3 is highly conserved and known to mediate lipid binding. We mutated this region (4xA) to test if it is essential for activation. Interestingly, membrane-enriched variants still triggered IL-1β secretion, whereas cytosolic 4xA failed.
5/9

All designed variants formed a functional inflammasome judged by ASC speck formation and their activation was K+ efflux-dependent.
4/9

We engineered NLRP3 to localize to different organelles: ER, Golgi, plasma membrane, lysosomes, mitochondria and peroxisomes. Surprisingly, all location-restricted variants supported IL-1β release when stimulated with different activators.
3/9

It is enigmatic how NLRP3 can be triggered by many different and unrelated signals. We wanted to know whether the subcellular location of NLRP3 plays a role.
2/9

Ever wondered where NLRP3 needs to be in the cell to activate the #inflammasome? Turns out, it does not really matter. Check out our latest study in
@natcomms.nature.com: nature.com/articles/s41...
See 🧵👇
1/9

Mechanisms of NLRP3 activation and inhibition elucidated by functional analysis of disease-associated variants
www.nature.com/articles/s41...
@natimmunol.bsky.social @sethlucianmasters.bsky.social