Project No.2260

Primary Supervisor

Dr Jenny Tullet – University of Kent

Co-Supervisor(s)

Dr Tim Fenton – University of Southampton

Summary

Obesity and age are major risk factors for a range of serious health issues.

Understanding how genetics, the nervous system, and the environment interact across life stages can help improve health and treat diseases. Many obesity-linked genes influence neuronal pathways that regulate eating behaviours. Appetite drives food intake, while satiety signals fullness, preventing overeating. Sensory and internal cues integrate to maintain homeostasis and prevent disease.

Our lab identified a genetic component in C. elegans, SKN-1/Nrf, which operates in a neuronal-physiological-behavioural axis to influence eating and metabolism. SKN-1/Nrf integrates environmental signals and modulates hormonal and neuromodulator pathways, altering behaviour and mitochondrial physiology (Tataridas-Pallas et al., 2021 PLoS Genetics).

Eating habits, metabolism, and body composition change with age. SKN-1/Nrf is a known longevity gene (Tullet et al., 2008 Cell; Tullet et al., 2017 Aging Cell), and food intake impacts age-related diseases like diabetes, cancer, and cardiovascular disease. Investigating SKN-1’s neurological role can link eating behaviors, longevity, and health, offering strategies to enhance population fitness.

The mammalian equivalent, Nrf, is expressed in the brain (hypothalamus) and regulates eating behaviour, suggesting a novel role in humans. This interdisciplinary project will explore SKN-1/Nrf function using C. elegans (Tullet lab) and mammalian cell culture (Fenton lab). Employing genetics, molecular and cellular biology, and physiological assays, we will map neurotransmitter circuits, uncover SKN-1/Nrf’s transcriptional role, and examine how disrupted eating behaviours affect mitochondria and whole-body physiology.