Characterization of Vps13 in Drosophila melanogaster

Kasravi, Kiana (2019) Characterization of Vps13 in Drosophila melanogaster. Masters thesis, Memorial University of Newfoundland.

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Abstract

Parkinson Disease (PD), the most common movement disorder, is a neurodegenerative disease that affects about 1% of the human population over the age of 65 years, and its prevalence increases with age. PD is clinically characterized by resting tremor, rigidity and bradykinesia as a result of the loss of dopaminergic neurons in the substantia nigra pars compacta in the mid-brain. Mitochondria play a significant role in PD. The PD candidate gene VPS13C was identified in human using whole-exome sequencing (WES). The VPS13C protein is involved in intracellular trafficking, especially lipid transportation, between the endoplasmic reticulum (ER) and other organelles, such as the late endosome/lysosome, as well as in the mitophagy pathway. I have successfully characterized the homologue of the human VPS13C gene in flies, Vps13. As a result, I have successfully modelled aspects of PD in Drosophila melanogaster. I found that inhibition of Vps13 improves the longevity and locomotor ability, while overexpression of Vps13 mostly reduced both the survival and locomotor abilities of flies. Furthermore, I have demonstrated that overexpression of Vps13 significantly influences neurodevelopment when expressed in the developing Drosophila melanogaster eye. Our final set of experiments focused upon the consequences of the inhibition and overexpression of Vps13 when expressed with the co-inhibition of parkin, a well-known PD gene. These co-expressions can give valuable insights into the genetic and/or functional connections between the two genes or their protein products. These findings suggest that the inhibition of parkin may improve the effects of Vps13 overexpression.

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