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• W3036339366 abstract "Parkinson’s disease is caused by a progressive loss of dopamine neurons inthe substantia nigra. A loss of motor control occurs in patients, with symptomsincluding bradykinesia, resting tremor and muscle rigidity. There is currently nocure for Parkinson’s disease and the commonly used treatment, L-DOPA, cancause side effects including dyskinesia. To identify potential treatments, drugscreening using a suitable animal model is required before reaching clinicaltrials. Zebrafish are a vertebrate model organism well suited for high throughputdrug screens, and genome editing can be used to create heritable mutations incausative genes to model human disease.This thesis presents five genetic models of Parkinson’s disease in the zebrafishcreated by CRISPR/Cas9 targeting (pink1, parkin, dj-1, fbxo7, and gba).Molecular analyses show a loss of dopamine neurons in the brain of the DJ-1deficient zebrafish. This thesis also presents findings from a transcriptomicanalysis of the dj-1 mutant brain revealing dysregulated genes consistent withknown parkinsonian defects.An important focus of this work is the development of a novel computationalmethod to analyse the movement phenotype of a zebrafish. The methoddeveloped uses high-speed recordings of zebrafish swimming, processed with anew fish tracking software. By measuring spatial coordinates and angles alongthe spine, swimming movement was converted into data suitable forcomputational analysis. The movement data was subjected to unbiasedanalysis employing a white-box supervised machine learning method (anEvolutionary Algorithm) which successfully discriminated the dj-1 mutant fromwild type.This thesis concludes that the DJ-1 deficient zebrafish is a representativeanimal model of Parkinson’s disease, and that machine learning can be used toclassify the model based on movement data alone. It is proposed that thetechniques developed here, have the potential for drug screens on the dj-1mutant using evolved classifiers to assess treatment effectiveness." @default.
• W3036339366 created "2020-06-25" @default.
• W3036339366 creator A5027155534 @default.
• W3036339366 date "2019-09-01" @default.
• W3036339366 modified "2023-09-27" @default.
• W3036339366 title "Machine learning discriminates parkinsonian movement disorders in zebrafish" @default.
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