Introduction and project rationale: Endogenous circadian rhythms are key in many physiological and behavioural processes in humans and changes in rhythms or desynchronization processes (for example, in shift workers) have been linked with adverse outcomes related to health and ageing. The central circadian clock is located in the hypothalamic suprachiasmatic nuclei and synchronises the timing of peripheral clocks in liver, muscle, gut and adipose tissue. Previous research has suggested that the central and peripheral circadian clocks are highly synchronised but recent research has implicated that misalignment between the central and peripheral clocks is a driver in ageing and development of chronic non-communicable diseases including obesity and type 2 diabetes. Understanding how the central and peripheral circadian clocks regulate metabolism or how these clocks are regulated by metabolic processes is hugely important, though limited research has currently been performed.
PhD research objectives:
Primary objective: To define the feedback and feed-forward links between the circadian timing system and metabolism in humans applying metabolomics and cellular molecular biology approaches
Secondary objectives: To experimentally define (1) how the central circadian clock in young and older healthy humans regulates metabolism or is regulated by metabolism; (2) how the peripheral circadian clocks in healthy humans regulates metabolism or is regulated by metabolism; (3) how acute and chronic changes to the central circadian clock effects peripheral clocks.
Research team:The supervisory team is built with experts in the areas of metabolism, metabolomics and statistical modelling (Professor Dunn, University of Birmingham), cellular molecular biology (Dr Dalmann, University of Warwick) and chronobiology (Professor Debra Skene, University of Surrey).
1. Dunn, W.B., Broadhurst, D.I., Atherton, H.J., Goodacre, R. and Griffin, J.L., 2011. Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chemical Society Reviews, 40(1), pp.387-426.
2. Davies, S.K., Ang, J.E., Revell, V.L., Holmes, B., Mann, A., Robertson, F.P., Cui, N., Middleton, B., Ackermann, K., Kayser, M. and Thumser, A.E., 2014. Effect of sleep deprivation on the human metabolome. Proceedings of the National Academy of Sciences, p.201402663.
3. Schmitt, K., Grimm, A., Dallmann, R., Oettinghaus, B., Restelli, L.M., Witzig, M., Ishihara, N., Mihara, K., Ripperger, J.A., Albrecht, U. and Frank, S., 2018. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell metabolism, 27(3), pp.657-666.