A number of diseases such as Alzheimer, Prion disease, Huntington, Diabetes II
are associated with protein misfolding and fibrillization (plaque formation).
Several experimental findings suggest that these diseases share generic
features that do not depend on the details of the amino acid sequence of
proteins, and that peptide-membrane interactions play an important role in this
context: On the one hand, membranes promote peptide aggregation under certain
circumstances. On the other hand, transient oligomeric peptide aggregates
induce membrane damage. An antibody has been identified that binds to
oligomeric aggregates associated with a wide range of diseases, and which
suppresses their membrane damaging activity upon binding. This indicates that
the toxic aggregates have a similar structure and that the mechanisms of
toxicity are generic.
Our long term goal is to study generic physical mechanisms governing the
interactions of membranes and amyloid-forming peptides by computer simulations.
With our study, we hope to contribute a deeper understanding of the mechanical
and thermodynamical basis of such amyloid-related diseases.
In the present project, we plan to lay the foundations for such a study and to
establish a suitable generic coarse-grained model.
This research project is carried out in close collaboration with Dr. Stefan Auer (University of Leeds)