Inflammasome is intracellular multiprotein complex composed of NLR receptor, adaptor ASC and a caspase-1. NLRP3 or cryopyrin is the most investigated receptor from the NLR family. Currently, we are researching the mechanism of NLRP3 inflammasome assembly. In order to define the roles of selected domains of NLRP3 in NLRP3 inflammasome assembly, 21 truncated NLRP3 mutants were expressed in NLRP3-deficient macrophages. We showed that mutants lacking LRR domain are fully responsive to various soluble and particulate instigators. We were able to define the minimal fully responsive NLRP3 variant, which is similar in length to some alternative splice variants. For shorter variants, which do not support activation, we were nevertheless able to show that they still respond to triggers, but fail in further steps of inflammasome assembly. We challenged several possible models of NLRP3 activation, including self-propagation model as proposed for homologous protein NLRC4, which seems not to be the case for NLRP3. These results were published in Hafner-Bratkovič* et al., Nature Communications, 2018. Our results were presented in forms of posters, selected talks and lectures on international conferences and meetings. This study was also selected for presentation at the Day of Slovenian Research Agency in 2019.
B.03 Paper at an international scientific conference
COBISS.SI-ID: 6730778We are also exploring the ways to inhibit NLRP3 inflammasome activation. Based on available structures of the proteins that comprise the inflammasome and on the NLRP3 regions, carrying pathological mutations, we designed two groups of putative inhibitory peptides, which are most likely to disrupt the formation of the inflammasome. Furthermore, we found that one peptide specifically inhibited the NLRP3 inflammasome and not other inflammasomes, and inhibited inflammasome activation in a mouse model of silica-induced peritonitis. Second revised version of manuscript Sušjan and coworkers & Hafner-Bratkovič* is to be submitted to FASEB J. PhD student (P.S.) was awarded L’Oreal for women in science PhD award.
B.03 Paper at an international scientific conference
COBISS.SI-ID: 6669594