Determination and analysis of systems properties of the milk-synthesizing metabolic network in bovine mammary glands

奶牛生产的牛奶含有对人类消费者具有营养和功能意义的蛋白质、脂肪和碳水化合物。这些成分在牛奶中的百分比含量和产量，以及牛奶的经济价值，可以根据奶牛的营养而变化很大。加拿大的乳制品行业花费了相当大的努力，通过营养和饲养奶牛来管理牛奶的成分，其中大约有100万头。饲料费用总计200万美元/天。该提案的目的是利用新的基因组技术来提高对如何确定牛奶的营养和非营养品质的理解，以便可以准确预测管理干预的结果。对决定奶牛总产奶量的因素的研究将涉及表征酶己糖激酶如何在乳腺上皮细胞内移动以适应产奶的需要，我们以前已经确定该酶对乳糖合成很重要。其次，我们将对乳腺中将血液氨基酸转化为乳蛋白的多个生化步骤进行全面的测量和分析，以确定生物控制在该途径中的位置。如果不知道控制点在哪里，就无法改变牛奶蛋白产量。第三，我们将对泌乳奶牛的乳腺组织进行活检，以分析表达的基因以及存在的蛋白质和化学代谢物。这些信息将用于在计算机中重建牛奶合成网络，以分析牛奶生产的潜在效率，牛奶成分的操作策略，并测试我们对牛奶是如何合成的理解。

The milk produced by cows contains proteins, fats and carbohydrates of nutritional and functional significance for human consumers. The percentage content and yield of these components in milk, and consequently the economic value of milk, can vary widely according to the nutrition of the cow. The dairy industry in Canada expends considerable effort to manage the composition of milk through nutrition and breeding of dairy cows, of which there are approximately 1 million. Feed costs total $2 million/day. The purpose of this proposal is to harness new genomic technologies to improve understanding of how the nutritive and non-nutritive qualities of cows' milk are determined so that the outcome of management interventions can be predicted with accuracy. Research into factors that determine total milk yield of a cow will involve characterizing how the enzyme hexokinase, which we have previously identified as being important for lactose synthesis, is moved around inside the mammary epithelial cell to accommodate needs for milk production. Secondly, we will conduct comprehensive measurement and analysis of the multiple biochemical steps that convert blood amino acids into milk proteins in the mammary glands in an attempt to pinpoint where the biological control lies in the pathway. Changes in milk protein yields cannot be engineered without knowing where the control points are. Thirdly, we will biopsy mammary tissue of lactating cows to profile the genes that are expressed and the proteins and chemical metabolites that are present. This information will be used to reconstruct in a computer the milk-synthesizing network for analysis of potential efficiencies of milk production, strategies for manipulation of milk composition, and to test our understanding of how milk is synthesized.