B07 Reif: Structural analysis of inhibitor-amyloid co-aggregates
The aim of the project is to obtain an understanding of the atomic mechanisms and interactions which determine whether an amyloidogenic peptide forms a fibril or aggregates into an amorphous or oligomeric structure. In particular, we will study the conformation of Aβ aggregates in presence of αB-crystallin, and characterise the conformational changes in comparison to Aβ fibril structure. In addition, we investigate cross-amyloid interaction surface mimic (ISM) inhibitors that efficiently prevent fibril formation and rescue cells from the cytotoxicity induced by Aβ. Furthermore, we will study the influence of other cellular components on the structure and the dynamics of the aggregates, which are commonly found co‑aggregated in vivo, such as glycosaminoglycans (GAGs) and serum amyloid P (SAP). The final goal is to understand how structural changes correlate with cellular toxicity.