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Title: The Characterization of the Pin1 Homolog, Dodo, in Drosophila Melanogaster
Authors: Przygonska, Paulina
Advisors: Notterman, Daniel
Department: Molecular Biology
Certificate Program: Global Health and Health Policy Program
Class Year: 2022
Abstract: Although traumatic brain injury (TBI) is associated with neurodegenerative disorders, the mechanisms underlying the association remain unclear. To study potential mediators in these mechanisms, Drosophila melanogaster has been increasingly used. Tau, a protein that mediates axonal transport and microtubule stabilization within the brain, becomes hyperphosphorylated, mislocalized, and forms aggregations in neurodegenerative disease. However, tau and its mediators have not been studied in the context of TBI-induced neurodegeneration in Drosophila. Though, Pin1, a prolyl isomerase, has been shown to isomerize tau and prevent tau-induced cellular toxicity in both traumatic brain injury and neurodegeneration, it remains unknown whether Dodo, the Drosophila homolog of Pin1, is also able to isomerize tau. Increasing evidence suggests that Pin-1 may induce apoptosis in neurodegenerative disease and that mitochondrial fission may mediate this Pin1-induced apoptosis. Thus, the presence study attempts to characterize the function of Dodo in Drosophila and its downstream effects on mitochondrial dynamics. Our work demonstrates that Dodo mutant flies exhibit significant decreases in median lifespan, trending decreases in mitochondrial DNA copy number and alterations in mitochondrial fission and fusion gene expression. Our work also shows vacuolization is present in the Drosophila Dodo mutant flies as soon as 9 days after eclosion. Our work suggests that Dodo plays a role in mediating mitochondrial dynamics, and its disruption may promote neurodegeneration. Therefore, the Dodo protein may be a suitable target for further investigation within the pathways underlying neurodegenerative disorders.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Molecular Biology, 1954-2022
Global Health and Health Policy Program, 2017-2022

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