slovenia 72
Kemijski Institut – KI , Slovenia
Address Hajdrihova 19 Ljubljana 1000 SI.

PI: Prof. Roman Jerala

Project Title: Endogenous Designed nanostructured vaccines based on polypeptides and TLR4 agonists.

Objectives: Training in bionanotechnology, conjugation chemistry, cellular and molecular biology, training in industry. Most effective vaccines are characterized by the simultaneous activation of innate immune response. Designed TLR4 agonist formulations will be based on the nanostructures composed of self-assembling polypeptide polyhedra and lattices (based on Gradišar et al., NatChemBIol 2013) conjugated with TLR4 agonists and antigenic polypeptides. Selected moieties responsible for the activation of immune response will be incorporated into the vertices of polypeptide nanostructures, to combine triggers that activate adaptive (i.e. B-cell or T-cell) and innate immune response (e.g. agonists of TLRs and NLRs) that act in a coordinated manner to promote maturation of the effective immune response. Functional moieties will be incorporated using both genetic coding of fusion polypeptides or by chemical conjugation.

Project Title: Endogenous TLR4 agonists

Objectives: Training in biochemistry, structural biology and pharmacology, training in industry. KI group recently discovered that oxidative stress triggers activation of TLR4 via formation of partially oxidized phospholipids that are able to activate TLR4 through binding to MD-2 similarly to LPS. This explains the pervasive role of TLR4 in so many different processes and the efficiency of TLR4 agonists for the therapy. This project will investigate the role of oxidized phospholipids and their synthetic analogues, in inflammation, characterize the molecular determinants of endogenous TLR4 agonists produced by oxidative stress and investigate the therapeutic efficiency of synthetic antagonists in preventing activation of TLR4 in sterile inflammation.