This project investigates the biological mechanisms underpinning resilience to sleep loss, with a particular focus on sex differences and the role of oxidative stress. Sleep disruption is a major public health concern, associated with impaired cognition, immune dysfunction, and increased metabolic and inflammatory risk. A growing body of evidence indicates that sleep loss leads to the accumulation of reactive oxygen species (ROS), and that this oxidative burden is a causal driver of adverse health outcomes rather than a passive by-product. Using Drosophila melanogaster as a genetically tractable model organism, this research tests the central hypothesis that females exhibit greater resilience to infection induced sleep loss due to tighter regulation of ROS, and that this resilience can be mimicked or enhanced through targeted nutritional antioxidant interventions.
The project combines behavioural, genetic, transcriptomic, and nutritional approaches across three integrated aims. First, ROS dynamics and sleep behaviour will be characterised in male and female flies during bacterial infection and mechanically induced sleep deprivation. Fluorescence based ROS detection methods will be paired with high throughput behavioural monitoring using ethoscope tracking to directly link oxidative load with changes in sleep and activity.
Second, the molecular mechanisms underlying female resilience will be identified by comparing male and female transcriptional responses to infection. Candidate antioxidant and redox regulating pathways will be functionally tested using the GAL4UAS system to genetically overexpress or knock down key enzymes such as superoxide dismutase, catalase, and glutathione transferases. This will establish causal links between specific molecular pathways, ROS regulation, and susceptibility or resilience to sleep disruption.
Third, the project evaluates the efficacy of oral nutritional antioxidants, in mitigating infection induced sleep loss. Supplement ingredients will be tested for their ability to restore sleep in susceptible males and to modulate ROS associated pathways. Translation beyond the fly model is embedded through an industrial placement at Unilever R&D Port Sunlight, where candidate ingredients will be assessed in preclinical human intestinal models, including Caco2 systems and/or organon chip platforms, to measure ROS responses in a human relevant context.
Broader and future implications: This research will deliver mechanistic insight into how oxidative stress links sleep disruption, immunity, and sex specific health outcomes. By providing proof of concept that nutritional antioxidants can reinforce resilience to sleep loss, it establishes a strong translational foundation for the development of sex informed, ingestible wellbeing interventions. In the longer term, the findings could inform personalised nutrition strategies, support innovation beyond traditional sleep aids, and contribute to improved approaches for managing the health consequences of chronic sleep insufficiency, particularly in women’s health and wellbeing.
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