Researcher ORCID Identifier
Open Access Senior Thesis
Bachelor of Arts
© 2023 Madeleine J Callan
Parkinson’s disease is a debilitating and often deadly neurodegenerative disease affecting a growing and large population. Its etiology has long remained elusive, and because no other organisms have Parkinsonian-like diseases, it is difficult to study PD using model organisms. Neuromelanin (NM), an insoluble melanin synthesized in the dopaminergic synthesis pathway in DA neurons, has recently been implicated in PD as a major causal factor. At high levels in DA lysosomes, it functions as a proteostatic pathway inhibitor–blocking dopaminergic neurons from breaking down harmful molecules until the lysosomes eventually degenerate as well as triggering autophagy, inflammation, and total neurodegeneration. Recently, neuromelanin was first artificially expressed for the first time in a model organism by way of AAV-injection of hTyr into the rat substantia nigra pars-compacta (SNpc). We attempted to produce a PD model in Drosophila melanogaster by way of UAS expression of hTyr that is comparatively accurate, broadly useful in PD research and provides different advantages than a NM rat model. We created this first ever Drosophila-compatible pUAST-hTyr plasmid by cloning a pUAST plasmid and a hTyr mammalian plasmid. We used young and old WT Canton S flies to gauge a climbing assay and activity monitor assay for usefulness for testing WT and hTyr flies on negative geotaxis, spontaneous activity and circadian rhythm patterns. While at the completion of this project the hTyr flies are still being mated to complete the transgenic line and thus no data for those flies is available, we soon will have achieved the creation of the first-ever pUASt-hTyr flies for PD research and have provided a comprehensive and complete launching point for the next project involving the hTyr fly line.
Callan, Madeleine, "Expression of hTyr in Drosophila as a Novel Model of Parkinson’s Disease" (2023). Scripps Senior Theses. 2082.