Engineering Growth Factor/Receptor Processes

该项目将联合收割机的方法， 细胞生物学和分子生物学， 增加对如何结合和 生长因子/受体相互作用的运输方面 影响哺乳动物细胞增殖， 这增加了对建议设计原则的理解 用于旁分泌和自分泌细胞培养系统。 表皮生长因子（EGF）及其受体（EGFR） 成纤维细胞系将作为焦点系统。 描述EGF/EGFR运输的数学模型 及其对外源性EGF对细胞生长的调节作用 在机械配体/受体参数方面， 是最近开发的，并经过实验验证。 这些模型现在将用于研究策略 对于细胞培养系统的扰动， 延伸到旁分泌和自分泌EGF来源。 的 扩展模型将通过构建 利用细胞的人工旁分泌和自分泌系统 用编码EGF和/或EGFR的基因转染。 通过定点突变对这些基因进行修饰 将允许系统的关键速率参数 直接变化。 这些研究将确定参数 可以有效地控制细胞生长 用于生物技术目的。

This project will combine approaches of biochemical engineering, cell biology, and molecular biology to increase quantitative understanding of how binding and trafficking aspects of growth factor/receptor interactions influence mammalian cell proliferation, and to exploit this increased understanding to suggest design principles for paracrine and autocrine cell culture systems. Epidermal Growth Factor (EGF) and its receptor (EGFR) on fibroblastic cell lines will serve as the system of focus. Mathematical models which describe EGF/EGFR trafficking and its effect on cell growth regulation by exogenous EGF in terms of mechanistic ligand/receptor parameters have been recently developed and experimentally validated. These models will now be used to investigate strategies for perturbation of cell culture systems, and will be extended to paracrine and autocrine EGF sources. The extended models will be critically tested by constructing artificial paracrine and autocrine systems using cells transfected with genes encoding EGF and/or EGFR. Modification of these genes by site-directed mutagenesis will allow key rate parameters of the system to be directly varied. These studies will identify parameters that can be usefully manipulated to regulate cell growth for biotechnological purposes.