Presentation

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.

Plaque


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.

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2019

2018

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My prion research is based on biophysical studies of recombinant human prion protein (HuPrP) as well as prion proteins from other species.

The prion work is performed in our P3** lab, situated next door to our regular lab environment.

In our strive to understand formation of plaques and aggregates in a number of different protein misfolding disease, such as Alzheimer´s disease and AA amyloidosis we use fluorescence microscopy with both conventional probes and novel probes developed in the lab of Peter Nilsson. This in combination with exploration of proteins from recombinant sources gives insight in propagation of different amyloid species in the affected tissue.

Publications
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2019

2018

2017

Jay Rasmussen, Jasmin Mahler, Natalie Beschorner, Stephan A. Kaeser, Lisa M. Haesler, Frank Baumann, Sofie Nyström, Erik Portelius, Kaj Blennow, Tammaryn Lashley, Nick C. Fox, Diego Sepulveda-Falla, Markus Glatzel, Adrian L. Oblak, Bernardino Ghetti, Peter Nilsson, Per Hammarström, Matthias Staufenbiel, Lary C. Walker, Mathias Jucker (2017) Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimers disease Proceedings of the National Academy of Sciences of the United States of America , Vol. 114 , s. 13018-13023 Continue to DOI

2016

Rodrigo Gallardo, Meine Ramakers, Frederik De Smet, Filip Claes, Ladan Khodaparast, Laleh Khodaparast, Jose R. Couceiro, Tobias Langenberg, Maxime Siemons, Sofie Nyström, Laurence J. Young, Romain F. Laine, Lydia Young, Enrico Radaelli, Iryna Benilova, Manoj Kumar, An Staes, Matyas Desager, Manu Beerens, Petra Vandervoort, Aernout Luttun, Kris Gevaert, Guy Bormans, Mieke Dewerchin, Johan Van Eldere, Peter Carmeliet, Greetje Vande Velde, Catherine Verfaillie, Clemens F. Kaminski, Bart De Strooper, Per Hammarström, Peter Nilsson, Louise Serpell, Joost Schymkowitz, Frederic Rousseau (2016) De novo design of a biologically active amyloid Science , Vol. 354 , s. 720-+ Continue to DOI

2015