"Quantitative Studies of Binding and Trafficking of Endogenous and Genetically-Altered Epidermal Growth Factor Receptors in Cultured Fibroblasts."

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Significant progress has been made during the past decade on identifying the molecular components of the regulation of mammalian cell proliferation by peptide growth factors and their cell surface receptors. Since this regulation underlies many current problems in the reliable and reproducible design of cell culture-based technologies, a translation of this progress into useful quantitative engineering terms is crucial. Preliminary studies are proposed to test the hypothesis that the mitogenic responsiveness of fibroblast cell lines to epidermal growth factor (EGF) is related to the trafficking properties of the EGF receptor. A variety of kinetic EGF binding and dissociation studies will be performed in order to estimate values for various trafficking constants in a mathematical model. These studies intend to determine whether any changes in trafficking parameters are correlated to proliferation responses. If this is so, a substantial research program along these lines will be motivated.