The impact of circadian desynchrony on cardiovascular function.

我们星球上的生物体使用内部生物钟预测环境中反复出现的波动。昼夜节律失调对人类的健康和福祉有着深远的影响。例如，长期轮班工作与肥胖、心血管疾病、糖尿病和癌症的发病率增加有关。我们最近发现，体内生物钟和外部光暗环境之间的去同步对小鼠的心脏功能有明显的影响。这个博士研究了为什么心血管系统特别容易受到昼夜节律紊乱的影响，并定义了相关的潜在机制。研究将集中在整个动物生理学上，并结合新的遗传和药理学技术来操纵时钟功能。这个项目将促进我们对心血管生理学的理解，并对与昼夜节律紊乱和早晨心脏猝死易感性相关的人类病理学提供重要的新见解。该项目通过我们对哺乳动物生理学的综合方法(从基因到整个动物生理学)、工具开发(通过用于体内基因表达分析的新成像技术)和使用计算方法来分析电生理数据，反映了BBSRC的新工作方式的倡议。具体地说，学生将在以下方面获得广泛的经验：i)研究整个动物生理学(生理监测、心电记录和行为评估；Ii)体外技术，包括心脏电生理学、收缩和起搏、体外细胞/组织培养和分子技术。iii)电生理数据的计算分析和基本编程。因此，该项目是一个极好的培训机会，采用了最新的技术，并为英国的研究基础设施贡献了重要的体内培训(目前不足)技能。

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.