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的健康和福祉的明显影响，促使人们对能量代谢和进食行为的兴趣和研究增加。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发挥着至关重要的作用，包括我们如何衰老、免疫系统的功能以及对伤害和疾病的反应。尽管人们对此给予了更多的关注并取得了最新进展，但对于能量代谢是如何在人体细胞和组织中进行调节的，生物钟等内部系统如何协调代谢反应以处理禁食和进食状态之间的反复循环，以及大脑和身体的调节过程如何适应环境、年龄、感染和疾病的变化，仍然存在根本的差距。我们的研究致力于解决这些问题。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，我们要求提供资金，以购买一个最先进的平台，在以前不可能的水平上研究老鼠和其他小型实验室动物。该系统允许在家养环境中对许多重要参数进行高精度的全自动和完全同步的评估(从而大大减少对动物的压力)。从单个动物身上同时收集所有这些指标的能力将使我们能够了解不同行为、饮食控制和新陈代谢过程之间的相互作用。该系统还提供非常严格的外部条件控制，如光线、温度和食物供应，这将使我们能够在一系列环境设置中进行研究(包括模拟更自然的条件)。该系统将为一系列正在进行的研究计划提供重大进展。这些包括了解i)大脑如何决定我们吃什么、什么时候吃以及吃多少；ii)生物钟如何组织我们身体中极其多样化的过程，以及它如何被我们24小时的现代社会破坏；iii)我们身体细胞中的精细遗传过程如何能够驱动新陈代谢和身体成分的巨大变化；iv)新陈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(微生物群)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.