- Universität Zürich > Medizinische Fakultät > Neuropathologie, Institut für > Prof. Dr. Adriano Aguzzi
- Nilsson
Completed Research Project
- Title / Titel
- Prion conformation probed by Conjugated Polyelectrolytes
- Summary / Zusammenfassung
- Prion diseases are believed to be associated with the conformational conversion of the normal cellular prion protein, (PrPC), to an infectious beta-sheet rich insoluble isoform denoted PrPSc [1-6]. According to the “protein-only” hypothesis [1, 7], the transmission of prion diseases does not require nucleic acids, and the infectivity of the misfolded prion protein is believed to be encoded entirely within the misfolded conformation. Nevertheless, the “protein only” hypothesis does not explain the prion strain phenomenon where prion proteins having the same primary sequence can give rise to different strains, associated with diverse disease profiles. It has been suggested that the prion strain phenomenon might be encoded in the conformation of the misfolded protein and that the conformation is the critical mediator of prion susceptibility [8-15]. However, simple, sensitive and versatile tools that can be used to distinguish between different prion strains are not available.
In this regard, we wish to develop assays using conformationally sensitive fluorescent conjugated polyelectrolyte (CP) probes that provide a direct link between spectral signal and protein conformation [16-21]. In addition, CPs have been used for extremely sensitive biosensor applications where detection down to the zeptomole (10-21) level or approximately 100 molecules, of certain molecules in a complex sample has been achieved [22]. Now we wish to explore the use of these molecules for prion detection, as these probes present a novel opportunity to explore conformation phenotypes within different prion strains. Furthermore, assays for gaining more information regarding the mechanism of PrP aggregate generation is needed, as the underlying etiology of plaque formation in prion diseases and the knowledge regarding the strain phenomenon is poorly understood. This project, development of CP probes assays for prion detection, might lead to experimental tools that can be used to gain basic insights into prion plaque formation, TSE conversion, species barriers, the highly efficient mechanism for prion transmission and diagnostic test for prion diseases. Two specific aims of the project are outlined below.
- Keywords / Suchbegriffe
- prion protein, detection, conjugated polyelectrolytes
- Project Leadership and Contacts /
Projektleitung und Kontakte Peter Nilsson, PhD (Project Leader) peter.nilsson@usz.ch
- Funding Source(s) /
Unterstützt durch - Forschungskredit der Universität Zürich
- In Collaboration with /
In Zusammenarbeit mit Profs. Peter Konradsson and Olle Inganäs, IFM, Linköping University Sweden
- Duration of Project / Projektdauer
- Nov 2006 to Oct 2007