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Congratulations to Alzbeta Cardova on her publication in Biochemical Journal

last modified Nov 22, 2017 11:05 AM

Congratulations to Alzbeta Cardova, 2014 cohort PhD student in the BBSRC DTP Programme, for publishing the paper Genetic human prion disease modelled in PrP transgenic Drosophila in Biochemical Journal.

 

Abstract

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt–Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrPSc, an abnormal isomer of the normal host protein PrPC, in the brain of affected individuals. PrPSc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila. We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophilatransgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila. Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host.

Read the full paper.

 

Alzbeta is researching the identification of genetic modifiers of prion replication and neurotoxicity in the lab of Dr Raymond Bujdoso in the Department of Veterinary Medicine at the University of Cambridge. As part of the BBSRC DTP Programme she completed rotation projects in Veterinary Medicine and at the Institute of Metabolic Science with Dr Giles Yeo. Alzbeta is currently undertaking an internship at Acidophil.