Strain Tropism and Host Response
Transmission of prions from various mammals to laboratory mice has led to the identification of different prion strains that infect different areas of the brain and cause different pathologies. This phenomenon is referred to as “strain tropism” The mechanism by which prion strains target specific brain areas and cause different diseases is unknown. A possible explanation for this tropism is that strains spread through anatomical connections through the central nervous system and thus only access certain brain areas in which they propagate. Alternatively, prion strains have access to many different brain areas but specifically target certain regions or cells.
The aim of this research is to better understand how prion strains choose their target cells and how the cell responds to the invasion and propagation of specific prion particles. We make use of both in vivo and in vitro systems that allow us to characterize in more detail the type of cells and the types of brain areas that can be infected by a specific prion strain. Specifically, the neuropathological changes produced by different strains in mice are compared with the changes observed in infected brain cell cultures to test to what extent infection of specific cells is influenced by access of prions to specific areas of the brain.
Using standard operating procedures implemented by both partners we study changes of gene expression in mice and in different cell types to identify differences and commonalities in cellular responses to prion infection. Finally, we explore if infected cells and tissues secrete molecules that can be used as potential biomarkers for disease progression.