Structure-function relationships of ligand recognition and signal transduction in TLRs and other pattern recognition receptors (Area A)

One aim of the lab is to characterize PRR signaling on the molecular and cellular level. To this end we are combining molecular, cell biological and biochemical experiments with in silico methods. Of special interest is how signaling complexes are formed and regulated by post-translational modification. This approach was recently applied to the TLR adaptor molecule MyD88 in which oncogenic mutations contribute to the formation of lymphoma (see also below). Our research showed that mutated MyD88 spontaneously forms signaling complexes, leading to constitutive NF-kB signaling (Avbelj Blood 2014). Similar studies are currently being conducted for the NLRP3 inflammasome and non-conventional members of the NLR family.

After identifying the pharmacologically tractable Bruton’s Tyrosine Kinase (BTK) as a novel regulator of the human NLRP3 inflammasome in myeloid cells (Liu J Allergy Clin Immunol 2017) and platelets (Murthy BBRC 2016), study of the role of BTK in NLRP3 dependent signaling and disease settings will be one of additional main objective in this work are