Sensing and Analyzing Stress During Protein Expression

描述(申请人提供)：细胞和生物体通过 高度复杂的基因、蛋白质和代谢物网络，在 演唱会。了解这些系统的功能和调节是一个主要的 后基因组时代生物医学和生物工程研究的目标。这些 多变量系统是高度动态的，其响应是非线性的。 因此，分离研究一种蛋白质或途径的传统方法 经常失败。需要一种新的范式来理解 调节细胞生化活动的相互关联的途径和网络 功能和控制细胞反应。途径分析的方法和 重建工作已经根深蒂固。现在需要的是联合起来 生物/生物技术和系统工程方法，创造研究 将这些方法结合起来并从中获取价值的手段。我们提出了一个 建模和实验的协同组合以开发和测试 用于表征和控制酵母反应的定量工具 对细胞施加压力。 本项目建议书描述了数学的发展和应用 用于模拟生物过程的细胞内现象的工具，以及 用于数据实时采集的分子水平传感器的研制 细胞生长和蛋白质表达。这些研究工具的效用 将对酵母中未折叠蛋白的反应进行评估 在表达单链抗体的过程中。

DESCRIPTION (provided by applicant): Cells and organisms function through highly complex networks of genes, proteins, and metabolites, working in concert. Understanding the function and regulation of these systems is a major goal of biomedical and bioengineering research in the post-genomic era. These multivariable systems are highly dynamic, and their responses are nonlinear. Therefore, traditional methods of studying one protein or pathway in isolation often fail. A new paradigm is required to understand the mechanisms by which interrelated pathways and networks of biochemical activities regulate cell functions and control cellular responses. Methods for pathway analysis and reconstruction are well established. What is needed now is to combine biological/biotechnology and systems engineering approaches, creating research instruments to integrate these methods and take value from them. We propose a synergistic combination of modeling and experimentation to develop and test quantitative tools for characterizing and controlling the response of yeast cells to stress. This project proposal describes the development and application of mathematical tools for modeling the intracellular phenomena of biological processes, and the development of molecular-level sensors for real-time acquisition of data during cell growth and protein expression. The utility of these research instruments will be evaluated on the unfolded protein response in the yeast Saccharomyces cerevisiae, during expression of a single-chain antibody.