Mutations of a Drosophila NPC1 gene confer sterol and ecdysone metabolic defects.

The molecular mechanisms by which dietary cholesterol is trafficked within cells are poorly understood. Previous work indicates that the NPC1 family of proteins plays an important role in this process, although the precise functions performed by this protein family remain elusive. We have taken a genetic approach to further explore the NPC1 family in the fruit fly Drosophila melanogaster.

Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis.

Loss-of-function mutations of the parkin gene, which encodes a ubiquitin-protein ligase, are a common cause of autosomal recessive juvenile parkinsonism (ARJP). Previous work has led to the identification of a number of Parkin substrates that implicate specific pathways in ARJP pathogenesis, including endoplasmic reticulum (ER) stress and cell cycle activation. To test the involvement of previously implicated pathways, as well as to identify novel pathways in ARJP pathogenesis, we are using genetic and genomic approaches to study Parkin function in the fruit fly Drosophila melanogaster.