Amyloids
Proteins are the work horses of the cell and are crucial for most of the chemistry and transport ongoing in any living organism. In order to perform its duty, the protein has to be active by acquiring the native state. Most proteins attain a unique three-dimensional fold, others are natively disordered. However, sometimes proteins lose the native state and 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 40 proteins are known to be associated with amyloid disease in humans.
Virus amyloids
My interest in virus proteins and in particular virus protein amyloids was triggered by the SARS-CoV-2 pandemic. I was struck by the similarities between symptoms of severe and long Covid and those of several amyloid associated diseases.
Mammalian proteins have evolved to prevent amyloid formation to keep us healthy during our extended lifetime. Viruses on the other hand do not benefit from a proteome with low propensity to form amyloid. And indeed, may virus proteins from different virus families form amyloid.
In our group we use protein science tools as well as in vivo models to investigate how virus derived protein sequences form amyloids in vitro. We also delineate how virus amyloids effect human proteins.
Group members in virus amyloid projects:
Post-doc: Debdeep Chaterjee
Master students: Vilma Odland, Henrik Westman, Ebba Hellstrand
Polymorphism of Amyloids and Prions
My research on amyloid structure 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 between 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.
Prions
The prion work is performed in our P3** lab, situated next door to our regular lab environment.
Some amyloids have infectious properties due to self-propagation. Among the infectious amyloids, prions are the most well-known. Herein native PrP is transformed into new amyloids by interactions with infectious prions. 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.
We use recombinant human prion protein (PrP) as well as prion proteins from other mammalian species to delineate molecular mechanisms behind the misfolding of this enigmatic protein. We also use PrP as a substrate protein when investigating possible cross-seeding mechanisms that might be involved in initiating prion disease.
