The overall objective is to apply physical-chemical rationale and techniques to the study of physiological and pathological processes involving lipids and specific proteins. Certain biological fluids (plasma, lymph, bile) contain lipids solubilized or suspended in aqueous systems frequently in association with specific proteins (e.g., lipoproteins). Disorders affecting lipid transport lead to the lipoproteinemias and often to a pathological distribution of lipids in tissues, cells, and fluids. Such disorders as atherosclerosis or gallstones may results. The plasma membranes of cells and/or intracellular organelles contain complex polar lipids which are not soluble but are structured in such a way as to combine fluidity with stability. Membrane composition varies from organelle to organelle and further, membranes are asymmetric with respect to both lipid and protein distribution. Membrane composition and symmetry can be altered by changes in the external environment or by internal metabolic perturbations and such changes may lead to defective function. Inherited deficiencies of enzymes involved in the catabolism of complex phospho- and sphingo-membranes, and lysosomes. These accumulations affect cell and organ function and give rise to the various familial lipidoses. Finally, certain less polar lipids (occurring for instance in adipose tissue, adrenal glands, gonads, liver and in the lesions of atherosclerosis) are organized in phases separated from the aqueous system. These phases may be liquid or more structure liquid crystalline or crystalline phases. The long term goals are to study the physical state and molecular interactions of lipids and proteins in living systems, to compare them to model systems, to learn how the physical state affects metabolism and vice versa, to understand the molecular basis and genetic control of lipoprotein secretion, interconversion, cell surface interaction and molecular exchange processes that occur in normal lipid transport, to understand the molecular basis of certain specific membrane functions and ultimately to understand the molecular basis of conditions in which lipids accumulate, such as atherosclerosis, the lipoproteinemias, and the lipidoses.
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