Novel targets for increased muscle growth or feed efficiency

据预测，从现在到2050年，全球粮食需求将会增加。如果粮食生产没有重大进展，粮食短缺将在全球范围内变得更加频繁，包括世界发达地区。因此，我们必须确保有足够的粮食来建立“全球粮食安全”。世界人口目前为70亿，但预计到2050年将增加到90亿。这是对粮食安全的重大威胁，但也存在其他加剧压力。有必要减少温室气体排放，以减缓全球变暖和气候变化，而土地和作物正越来越多地用于生产化石燃料（煤、天然气和石油）的替代能源。这导致了对土地、水、能源和食物来源本身的竞争。要生产更多的粮食，要么需要更多的土地（这是不可用的），要么需要提高生产效率。预计发展中国家个人财富的增加将增加对肉类和动物产品的需求，消费者将肉类和动物产品与更高质量的饮食和社会地位联系在一起。然而，生产肉类比生产其他食物需要更多的资源。肉类生产动物，如猪和家禽，通常需要谷物饲料，由于来自人类饮食和生物燃料行业的竞争，谷物饲料将成为越来越有限的资源。这些压力使得减少每单位肉类（或其他产品）所需的饲料量变得非常重要，从而提高“饲料效率”。要做到这一点，就需要使用技术，包括那些目前被认为不被消费者接受的技术（至少在欧盟），尽管对食品安全的威胁可能会改变消费者的价值观和道德立场。为了有效地生产肉类，目标是最大限度地将营养物质（特别是蛋白质）沉积到骨骼肌中，并将营养物质（特别是能量）从脂肪中重新分配出去。动物生长促进剂在一些国家（澳大利亚、巴西和美国）是合法使用的，但在欧盟却不是，它们具有增加瘦组织质量、减少体脂的效果。我们的目标是识别新的基因，更具体地针对合成代谢和/或能量节约机制，比目前可用的化合物更有效，更环保/更安全。诺丁汉大学最近的工作将动物研究与肌肉、肝脏、脂肪组织和血液代谢物基因的系统生物学分析结合起来，发现了一些新的基因，这些基因的表达与肌肉生长的增加有关。重要的是，这项工作正在进行中，因此将继续识别潜在的靶基因，直到2015年。因此，本项目的目的是验证这些新的靶基因是否真的能提高肌肉生长和/或饲料效率。这将首先在肌肉细胞培养研究中进行，从而增加或减少单个目标基因，并确定对肌肉细胞生长的影响。这项工作将首先使用小鼠C2C12肌肉细胞系，然后是猪原代卫星细胞。然后将在小鼠中研究从肌肉细胞培养工作中选择的靶标，通过在肌肉中再次增加或减少靶基因的表达，或注射靶蛋白或相关药物，并通过重复CT扫描和使用代谢笼测量饲料效率来非侵入性地监测肌肉生长。我们期望能够鉴定出提高肌肉生长效率的特定基因，从而成为未来开发药物的靶标，从而增加肌肉生长并提高饲料效率。

An increase in the global demand for food is predicted between now and 2050. Without major advances in food production, food shortages will become more frequent across the globe, including developed parts of the world. It is therefore essential that we ensure sufficient food is available to establish "global food security". The world population currently stands at 7 billion but is predicted to increase to 9 billion by 2050. This is a major threat to food security, but there are also other exacerbating pressures. There is a need to reduce greenhouse gas emissions to reduce global warming and climate change, while land and crops are being increasingly used to produce alternative energy sources to fossil fuels (coal, gas and oil). This leads to competition for land, water, energy and the sources of food themselves. To produce more food requires either more land (which isn't available) or an improvement in the efficiency of production. Increases in personal wealth in developing countries is predicted to increase the demand for meat and animal products, which consumers associate with a higher quality diet and social status. However, meat requires significantly more resource to produce than other foods. Meat producing animals, such as pigs and poultry, commonly require grain-based feeds which will become an increasingly limited resource, due to competition from human diets and the biofuels industry. These pressures make it important to reduce the quantity of feed required per unit meat (or other product) produced, thereby improving "feed efficiency". To do this, use of technologies will be required including those not currently deemed acceptable to the consumer (in the EU at least), although threats to food security may change consumers values and ethical stances. For efficient production of meat, the goal is to maximize the deposition of nutrients (particularly protein) into skeletal muscle and repartition nutrients (particularly those for energy) away from fat. Animal growth promoters are used legally in some countries (Australia, Brazil and USA), but not the EU, and have the effect of increasing lean tissue mass while decreasing body fat. Our aim is to identify novel genes that more specifically target an anabolic and/or energy-sparing mechanism and are more efficacious and greener/safer than the currently available classes of compounds. Recent work at Nottingham combining animal studies with systems biology analyses of genes in muscle, liver and adipose tissue and blood metabolites has identified a number of novel genes whose expression is associated with increased muscle growth. Importantly, this work is ongoing and therefore will continue to identify potential target genes to 2015. The objective of this project is therefore to verify whether these novel target genes really can improve muscle growth and/or feed efficiency. This will be done initially in muscle cell culture studies, whereby the individual target genes will be increased or decreased and the effect on muscle cell growth determined. This work will be done initially using the mouse C2C12 muscle cell line, then primary pig satellite cells. A selection of targets from this muscle cell culture work will then be studied in mice, whereby expression of the target gene will again be increased or decreased in muscle or the target protein or a related drug will be injected and muscle growth monitored non-invasively over time by repeated CT scanning and feed efficiency measured using metabolic cages. The expectation is that specific genes will be identified which enhance the efficiency of muscle growth and which could therefore be targets for drugs to be developed in the future that will increase muscle growth and improve feed efficiency.