Amyloid and Prion Polymorphism
(Abstract from my docent lecture held 14 June 2018)
Proteins are the work horses of the cell and are crucial to most of the chemistry and transport ongoing in any living organism. In order to perform its duty, the protein has to be active. To meet this requirement proteins acquire their native state. Most proteins adapt a unique three dimensional fold, others are natively disordered. However, sometimes proteins leave the native state form a misfolded state. This can be detrimental to the host cell, the host organ and ultimately the host organism.
A subclass of misfolded states are known as amyloids. Amyloids are large depositions of well-structured bundles of misfolded proteins. They can be found in any organ of the body and over 30 proteins are known to be associated with amyloid disease in humans. Some of these amyloids have infectious properties due to self-propagation. Among the infectious amyloids, prions are the most well-known. Prions became infamous during the mad cow disease (BSE) epidemic in the 1980ies and the cases of human Creutzfeldt-Jakob disease that followed in its trail.
My research focuses on delineating differences in amyloid structure - amyloid polymorphism - using a combination of recombinant expressed proteins, animal models of disease, biophysical techniques and novel fluorescent probes. It is of utter importance to understand the differences of these structures. Prion strains and their characteristics are good examples of the impact of structural polymorphism on disease progression. A molecular understanding of the amyloid structures, what dictates their formation and rearrangement and what amyloid species are most malignant for the host will facilitate design of new diagnostic tools and more adequate and precise treatment regimens.
