Metabolic and behavioural phenotyping system

肥胖和代谢性疾病在英国社会的流行，以及现代生活和饮食对我们健康和福祉的明显影响，推动了人们对能量代谢和喂养行为的兴趣和研究的增加。人们也越来越认识到，营养、能量供应和新陈代谢在我们生物学的各个方面都起着至关重要的作用，包括我们如何衰老、免疫系统的功能以及对损伤和疾病的反应。尽管人们对能量代谢的关注越来越多，最近也取得了一些进展，但在了解能量代谢如何在身体的细胞和组织中受到调节，体内系统（如生物钟）如何协调代谢反应以应对禁食和进食状态之间的循环，以及大脑和身体中的调节过程如何适应环境、年龄、感染和疾病的变化等方面，仍然存在根本性的差距。我们的研究努力解决这些问题。这项工作的基础是研究和描述动物行为和生理的基本方面的能力。在这项提案中，我们要求拨款购买最先进的平台，以研究老鼠和其他小型实验动物，这在以前是不可能的。该系统允许在家庭笼环境中对许多重要参数进行高精度的完全自动化和完全同步的评估（从而大大减少了动物的压力）。从单个动物身上同时收集所有这些数据的能力将使我们能够了解不同行为、饮食控制和代谢过程之间的相互作用。该系统还提供了对光、温度和食物供应等外部条件的严格控制，这将使我们能够在一系列环境设置中进行研究（包括模仿更自然的条件）。这一系统将为范围广泛的正在进行的研究方案提供重大进展。其中包括理解1)大脑如何决定我们吃什么、什么时候吃、吃多少；Ii)生物钟是如何组织我们身体中各种各样的过程的，以及它是如何被24小时的现代社会破坏的；Iii)在我们身体细胞中运行的精细遗传过程如何驱动新陈代谢和身体组成的巨大变化，iv)代谢状态如何对我们的免疫系统在疾病或感染期间的工作状况产生如此重大的影响，以及v)我们肠道中的细菌（微生物组）如何对新陈代谢和免疫系统产生重大影响。

The prevalence of obesity and metabolic disease in UK society and the clear impact of modern life and diet on our health and wellbeing, has driven increased interest and research into energy metabolism and feeding behaviour. There is also an increasing recognition that nutrition, energy supply and metabolism play an essential role in diverse aspects of our biology, including how we age, functioning of our immune system, and response to injury and disease. Despite this increased focus and recent advances, there remain fundamental gaps in understanding about how energy metabolism is regulated across the cells and tissue of the body, how internal systems such as the body clock orchestrate metabolic responses to deal with recurrent cycling between fasted and fed states, and how regulatory processes in the brain and body adapt to changes in environment, age, infection and disease. Our research strives to address these questions.Underpinning this work is the ability to study and characterise fundamental aspects of animal behaviour and physiology. In this proposal we are requesting funds for the purchase of a state-of-the-art platform to study mice and other small laboratory animals at a level not previously possible. This system allows fully automated and perfectly synchronized assessment of numerous important parameters with high precision in a home-cage environment (thus greatly reducing stress to the animals). The ability to collect all of these measures simultaneously, from individual animals will allow us to understand the interaction of different behaviours, diet manipulations and metabolic processes. The system also provides very tight control over external conditions such as light, temperature, and food availability, which will allow us to conduct studies in a range of environmental settings (including mimicking more natural conditions).This system will provide significant advance to a wide range of ongoing research programmes. These include understanding i) how the brain dictates what, when, and how much we eat; ii) how the body clock organises hugely diverse processes across our body, and how it being undermined by our 24hr modern society; iii) how fine genetic processes operating in the cells of our body can drive huge shifts in metabolism and body composition, iv) how are metabolic state has such a major influence on how well our immune system works during disease or infection, and v) how bacteria in our gut (the microbiome) can have a major influence on both metabolism and the immune system.