Project Title:

Identification of genetic modifiers of mammalian prion disease modelled in Drosophila

Prjoect Summary:

Prion diseases are fatal and transmissible neurodegenerative diseases of humans and other animals. They are caused by the protein PrPSc, which is a misfolded form of the normal cellular prion protein, PrPC. These diseases are studied experimentally using animal models, and PrP transgenic Drosophila have been developed relatively recently as a rapid and tractable model of prion diseases. My project will use transgenic Drosophila infected with mammalian prions to help the identify gene expression changes that occur in cells during prion disease. These Drosophila will be transgenic for both PrP and a molecularly-tagged ribosomal subunit, allowing actively-translated mRNA to be isolated from specific cell types. Gene expression changes caused by prion infection will be determined by RNAseq, then candidate genes will be assessed for their ability to modify disease using RNAi and transgene overexpression in prion infected PrP transgenic Drosophila. This will help to advance the understanding of the molecular processes involved in prion-induced toxicity.