Membranes and metabolism: insights from invertebrates and lower vertebrates

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The proposed research uses animal models to establish how membrane/protein interactions are involved in the compartmentation and regulation of metabolism. An important aspect of my scientific approach is to attempt to relate several levels of organization (whole animal, tissues, cells, organelles and molecules) with the broad goal of establishing how membranes and their embedded proteins are designed to connect these levels of organization. I have three areas of emphasis Two involve membranes and their associated proteins. For these we will focus on two membrane proteins of enormous importance to all animal cells (Na/K ATPase (NKA) and cytochrome c oxidase (CCO)). NKA is an ATP-consuming ion pump that has been estimated to account for about 25% of the energy needs (ATP) of a typical cell while CCO is part of the ATP producing electron transport chain (ETC) responsible for 85% of aerobic ATP production. These two proteins reside in very different membranes (the cholesterol-free mitochondrial membrane and the cholesterol-rich plasma membrane respectively). These two models thus capture many important elements of the links between membranes and metabolism. The third area of emphasis involves the compartmentation and kinetics of nitrogen metabolism from the whole organism to the cellular and subcellular levels. Taken together the proposed studies will provide a better understanding of the how membrane lipid/protein interactions are involved in mediating the ATP-producing and ATP-consuming processes in cells. At higher levels of organization, they will establish some of the "rules" for the design of exchange of metabolites between the blood and tissues. Our current understanding of these phenomena is rudimentary and thus these studies will be of broad applicability to all multicellular animals.