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dc.contributor.authorCardova, Alzbeta
dc.date.accessioned2019-03-11T10:27:49Z
dc.date.available2019-03-11T10:27:49Z
dc.date.issued2019-07-20
dc.date.submitted2018-09-10
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/290412
dc.description.abstractThe aim of my thesis was to develop and characterise PrP transgenic Drosophila melanogaster of various genotypes to study the process of prion-induced neurodegeneration in this model. Prion diseases are caused by the occurrence of an abnormally-folded form of PrP (PrPSc) protein that arises either from the environment as an acquired disease, from mutation in the PrP-coding gene as a genetic disease or sporadically from causes unknown. The PrPSc then recruits PrPC, the normal form of PrP, that is ubiquitously present in the mammalian CNS and triggers neurotoxicity and neurodegeneration that is transmissible between individuals of the same or even different species. All prion diseases are currently incurable, fatal and the mechanism of prion-induced neurodegeneration remains to be discovered. In this thesis, Drosophila transgenic for ovine (chromosome 3 and dual PrP transgenic flies), hamster, humanised murine, human and cervid PrP were characterised for expression and biochemical properties. The ultimate goal of my thesis was investigation of cell-to-cell spread of misfolded PrP in Drosophila CNS. To achieve this, a mutant form of PrP that is thought to misfold was co-expressed with the normal form PrPC that served as a substrate in the same dual PrP-transgenic fly. The process was modelled using hamster, humanised murine or ovine PrP transgenes that carry human mutations associated with the spontaneous onset of transmissible neurodegeneration in the natural host. Various approaches towards independent spatial expression of PrP in Drosophila were exploited here in both single and dual PrP expressing flies. Moreover, the ability to initiate misfolding and the impact of this on the fly phenotype was investigated. Both apparent misfolding and phenotypic changes were seen in different fly models suggesting the models were successful. To this extent, PrP transgenic Drosophila were developed to allow for relatively rapid modelling of mammalian prion disease in this invertebrate organism.
dc.description.sponsorshipBBSRC DTP
dc.language.isoen
dc.rightsAll rights reserved
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectprion
dc.subjectDrosophila
dc.subjectprotein
dc.subjectmisfolding
dc.subjectneurodegeneration
dc.subjectPrP
dc.subjectaging
dc.subjectprion disease
dc.titleModelling prion-induced neurodegeneration in PrP transgenic Drosophila
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentVeterinary Medicine
dc.date.updated2019-03-11T10:12:29Z
dc.identifier.doi10.17863/CAM.37641
dc.publisher.collegeWolfson College
dc.type.qualificationtitlePhD in Bioscience
cam.supervisorBujdoso, Raymond
cam.thesis.fundingtrue


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