Understanding the molecular mechanisms of protein folding, misfolding and aggregation is the major objective of this project. We develop time-resolved infrared-spectroscopic techniques to study structure formation on different time scales. Formation of sheets are analysed on the level of individual amino acids using model peptides and site-specific probes. We design peptide templates with polyglutamine (polyQ) sequences to mimic monomeric structural motifs of a fibril. Backbone ordering and side chain packing will be studied separately in order to shed light onto fibril formation in polyQ diseases. Furthermore, we will extend our IR studies on the intrinsically disordered Parkinson disease protein -synuclein and explore the potential regulatory role of other naturally occurring synuclein variants within the aggregation process. Interaction of aggregates with membranes and membrane damage will be characterized in molecular details.
DFG Programme
Collaborative Research Centres
