The role of evolutionary conserved microRNAs in feeding and nutrition

食欲和能量代谢的协调调节是终身健康的基础。这定义了关键的能量依赖有机体参数，如生长速度、大小、繁殖潜力、行为和宿主防御能力。控制不当会导致一系列饮食和代谢紊乱。我们最近进行了一项基因筛选，以确定果蝇这种简单生物的摄食和生长的新分子调节因子，并发现一系列被称为microRNAs的非编码rna在决定摄食方面起着重要作用。重要的是，从昆虫到哺乳动物，这些microrna中的一些及其靶基因在进化上是保守的，其中一些代表了参与激素控制能量代谢的潜在新调节器。该合作项目旨在研究新的进化保守的microrna在果蝇和哺乳动物的喂养和营养中的作用。具体来说，我们将：1。利用果蝇现有的先进遗传工具，定义在microrna缺乏的背景下受影响的系统、器官和细胞成分，然后应用一系列分子生物学和生理学方法来测试microrna在受影响细胞和器官的生理学中的作用。2. 我们将分析新的保守microrna在代谢相关的哺乳动物组织（饮食诱导和遗传性肥胖小鼠模型）以及瘦和肥胖受试者的人体组织中的表达。这将通过使用独特的基因改变体外模型来分析新型microrna靶向的信号机制来补充。3. 采用发现方法筛选可能阐明果蝇和哺乳动物对能量密集食物偏好的进化保守机制的microrna。该项目将阐明新的分子调控和机制，可能支持进化保守的遗传基础的营养和代谢。

Fundamental to life-long health is the coordinated regulation of appetite and energy metabolism. This defines key energy-dependent organismal parameters such as growth rates, size, reproductive potential, behaviour and host defence capabilities. Inappropriate control can result in a range of eating and metabolic disorders. We have recently performed a genetic screen to identify novel molecular regulators of feeding and growth in a simple organism, the fruit fly and found that a range of non-coding RNAs termed microRNAs plays important roles in defining feeding. Importantly, several of these microRNAs and their target genes are evolutionarily conserved from insects to mammals and some of these represent potentially novel regulators involved in hormonal control of energy metabolism. This collaborative project aims to investigate the roles of novel evolutionarily conserved microRNAs in feeding and nutrition in flies and mammals. Specifically, we will: 1. Exploit advanced genetic tools available in Drosophila, to define the systems, organs and cellular components affected in microRNA-deficient backgrounds and then apply a range of molecular biology and physiological approaches to test the roles of microRNAs within the physiology of affected cells and organs. 2. We will profile the expression of novel conserved-microRNAs in metabolically relevant mammalian tissues mouse models of diet-induced and genetic obesity and in human tissues from lean an obese subjects. This will be complemented by use of unique genetically altered in vitro models to dissect the signalling mechanisms targeted by novel microRNAs. 3. Take a discovery approach to screen for microRNAs that may elucidate evolutionarily conserved mechanisms that underpin food preferences for energy dense food in drosophila and mammals. The project will elucidate new molecular regulators and mechanisms that may underpin evolutionarily conserved genetic basis of nutrition and metabolism.