Amyloid fibrils

Amyloid fibrils – towards inhibition, design optimization and early-stage detection

Our aim is to explore in detail the formation and disintegration of fibrils on all levels from monomers and small oligomers in solution, through their interactions with membranes, proteases, metals, and small molecules to the formation of macroscopic amyloid fibrils with different conformation and heterogeneity. These steps will be followed systematically by combining biophysical methods with NMR and MD when sufficient structural information is available to explore natural and synthetic variants of A!, glucagon, "-synuclein, and calcitonin but may also involve more exotic systems such as "1PI in relation to lung diseases, fibrils involved in malaria, immunoglobulin light-chain amyloids, amyloids identified through -omics (transcriptomics, proteomics, metabonomics) protocols in vivo and bacterial fibrils from biofilm colonies. The latter is a shining example of functional amyloid and we will combine structural and functional analysis to elucidate principles for more robust self-assemblies with potential nanotechnological applications. We will explore interactions between fibrils and small polyaromatic organic compounds, as well as the role of enzymes such as transglutaminase on fibril formation, both classes of which may be used to stabilize and accumulate distinct populations of prefibrillar aggregates for detailed structural and functional characterization. A major goal is the systematic development of fibril inhibiting/decomposing compounds as well as compounds for improved early-stage detection and localization by MRI and PET.