Biological mechanisms of control of milk synthesis in mammary glands

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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. Costs of feed total $2 million/day. The purpose of this proposal is to harness the techniques of computer modelling, cell culture and parenteral nutrient infusion 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. A computer model of the delivery of nutrients to the mammary glands and their subsequent conversion into milk components will be updated and tested for its ability to predict responses of cows to infusion of glucose and a vasodilator into the mammary arterial supply. In mammary epithelial cells in culture, we will characterize how the enzyme hexokinase, which we have previously identified as being important for lactose synthesis, is moved around to accommodate needs for milk production. Then we will conduct comprehensive measurement and analysis of the multiple biochemical steps that convert extracellular glucose into lactose in an attempt to pinpoint where the biological control lies in the pathway. Lactose synthesis is the major determinant of daily milk volume. Finally, the mechanism by which the concentration of milk precursors outside the milk secretory cell is communicated to the protein-synthesizing machinery inside will be studied. We will observe the timecourse of events in the signalling pathway and then build a computer model to simulate those observations. The computer models we build can be used to analyze potential efficiencies of milk production, strategies for manipulation of milk composition, and test our understanding of how milk is synthesized.