The impact of circadian desynchrony on cardiovascular function.

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Organisms on our planet use internal biological clocks anticipate recurring fluctuations in the environment. Dysfunction of the circadian system has a profound impact on human health and wellbeing. For example, chronic shift work is associated with increased incidence of obesity, cardiovascular disease, diabetes, and cancer. We recently revealed that desynchrony between the internal circadian clock and the external light-dark environment has a pronounced effect on cardiac function in mice. This PhD examines why the cardiovascular system is particularly vulnerable to circadian dysfunction, and defines underlying mechanisms involved. Studies will focus on whole animal physiology and incorporate novel genetic and pharmacological techniques to manipulate clock function. This project will advance our understanding of cardiovascular physiology, and provide important new insight into human pathologies associated with circadian disruption and morning susceptibility to sudden cardiac death.The project reflects the BBSRC 'new ways of working' initiative through our integrative approach to mammalian physiology (from gene to whole animal physiology), tool development (through novel imaging techniques for in vivo analysis of gene expression) and the use of computational approaches to electrophysiological data analyses.Specifically, the student will gain extensive experience in:i) The study of whole animal physiology (physiological monitoring, ECG recording, and behavioural assessment; surgical procedures, in vivo models of clock dysfunction, genetic targeting and environmental manipulation).ii) Ex vivo techniques including the study of cardiac electrophysiology, contractility and pacing, in vitro cell/tissue culture, and molecular techniques.iii) Computational analyses of electrophysiological data and basic programming.Therefore, this project represents an excellent training opportunity, employing the latest technologies and contributing vital in vivo training (currently underrepresented) skills to the UK research infrastructure.