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Research Synopsis
Cell lines are an invaluable tool for studying complex processes and diseases. Cell culture systems to study prion biology are limited to a few cell lines susceptible to either mouse-adapted or sheep prion strains, with none yet described able to stably propagate human prions.
We aim to develop cells that can propagate human variant and sporadic Creutzfeldt-Jakob disease prions by using a “silencing-reconstitution strategy” that recapitulates the approach used to make mouse models of human prion disease. This will enable us to develop a robust highly sensitive, automated cell culture assay for human prion infectivity.
Recent work has suggested prions themselves are not directly toxic but lead to the production of a toxic species. To identify the toxic species, we have developed a multi-parametric high content imaging assay of neurotoxic phenotypes. We will use this assay to examine toxicity through the course of a prion infection, isolate the toxic species and investigate the mechanism of action.
Cell lines are an invaluable tool for studying complex processes and diseases. Cell culture systems to study prion biology are limited to a few cell lines susceptible to either mouse-adapted or sheep prion strains, with none yet described able to stably propagate human prions.
We aim to develop cells that can propagate human variant and sporadic Creutzfeldt-Jakob disease prions by using a “silencing-reconstitution strategy” that recapitulates the approach used to make mouse models of human prion disease. This will enable us to develop a robust highly sensitive, automated cell culture assay for human prion infectivity.
Recent work has suggested prions themselves are not directly toxic but lead to the production of a toxic species. To identify the toxic species, we have developed a multi-parametric high content imaging assay of neurotoxic phenotypes. We will use this assay to examine toxicity through the course of a prion infection, isolate the toxic species and investigate the mechanism of action.
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