Ameena Khan Sullivan
ºÚÁÏÉç
My research project
Ambulatory tracking of human biological rhythms through metabolic profilingA critical challenge in circadian rhythm research is how to monitor the response of human peripheral clocks to circadian misalignment as is experienced during shift work. Using metabolic profiling (metabolomics) we have already shown that simulated shift work causes abrupt shifts in the timing of blood metabolites (1). These shifts likely reflect misalignment of the food-entrained peripheral clocks relative to the light-entrained central circadian clock located in the hypothalamus. This project is highly innovative and will validate a new way to track hormones and metabolites before and during simulated shift work. A novel ambulatory device, U-RHYTHM (2), has been developed that is capable of ambulatory, stress-free sampling of human interstitial tissue fluid every 20 minutes. This is a unique method to perform high-resolution sampling of peripheral clocks in humans. Using our established targeted LC-MS/MS metabolomics platform (3,4,5) the effect of shift work and the associated mistimed feeding and sleep on metabolite and hormone rhythms in plasma and interstitial fluid will be assessed. Validation of U-RHYTHM will open up new opportunities to study real life work practices in our 24-hour society.
References
- Skene DJ et al., Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proc Natl Acad Sci USA (2018) 115, 7825-7830.
- Davies SK, …Skene DJ Effect of sleep deprivation on the human metabolome. Proc Natl Acad Sci USA (2014) 111,10761-10766.
- Isherwood CM, Van der Veen DR, Johnston JD, Skene DJ 24-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes. FASEB J (2017) 31,5557-5567.
- Honma A, ….Skene DJ. Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females. Eur. J. Neurosci. (2020) 51,366-378.
Supervisors
A critical challenge in circadian rhythm research is how to monitor the response of human peripheral clocks to circadian misalignment as is experienced during shift work. Using metabolic profiling (metabolomics) we have already shown that simulated shift work causes abrupt shifts in the timing of blood metabolites (1). These shifts likely reflect misalignment of the food-entrained peripheral clocks relative to the light-entrained central circadian clock located in the hypothalamus. This project is highly innovative and will validate a new way to track hormones and metabolites before and during simulated shift work. A novel ambulatory device, U-RHYTHM (2), has been developed that is capable of ambulatory, stress-free sampling of human interstitial tissue fluid every 20 minutes. This is a unique method to perform high-resolution sampling of peripheral clocks in humans. Using our established targeted LC-MS/MS metabolomics platform (3,4,5) the effect of shift work and the associated mistimed feeding and sleep on metabolite and hormone rhythms in plasma and interstitial fluid will be assessed. Validation of U-RHYTHM will open up new opportunities to study real life work practices in our 24-hour society.
References
- Skene DJ et al., Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proc Natl Acad Sci USA (2018) 115, 7825-7830.
- Davies SK, …Skene DJ Effect of sleep deprivation on the human metabolome. Proc Natl Acad Sci USA (2014) 111,10761-10766.
- Isherwood CM, Van der Veen DR, Johnston JD, Skene DJ 24-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes. FASEB J (2017) 31,5557-5567.
- Honma A, ….Skene DJ. Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females. Eur. J. Neurosci. (2020) 51,366-378.