The role of evolutionary conserved microRNAs in feeding and nutrition

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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.