Role of the endosomal pathway in regulating sleep and circadian rhythms

Ageing and many neurodegenerative disorders are characterized by a progressive loss of neurons in particular brain regions leading to behavioural changes including cognitive decline, sleep disruption and circadian dysregulation. The endosomal pathway is a key regulator of protein degradation and recycling. Dysfunctional endosomes and dysregulation of proteins involved in trafficking and sorting cargo along the endocytic pathway are a hallmark of many neurological conditions including Alzheimer’s and Parkinson’s disease. Circadian rhythms are driven by cellular transcription-translation feedback loops. This project will investigate how endosomal dysfunction affects the molecular mechanisms underlying circadian clocks. It will use molecular, genetic and behavioural approaches in Drosophila to investigate the role of particular endosomal proteins, initially CHMP2B, and associated ESCRT complex machinery in regulating sleep and circadian rhythms.

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