Sensing and Analyzing Stress During Protein Expression

描述（由申请人提供）：细胞和生物体通过 基因、蛋白质和代谢物的高度复杂网络， 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，并且它们的响应是非线性的。 因此，传统的研究一种蛋白质或途径的方法是孤立的， 经常失败。需要一种新的范式来理解 生物化学活动的相互关联的途径和网络调节细胞 功能和控制细胞反应。途径分析方法和 重建工作已经建立。现在需要的是将联合收割机 生物/生物技术和系统工程方法，创造研究 工具，以整合这些方法，并从他们的价值。我们提出了一个 建模和实验的协同结合，以开发和测试 用于表征和控制酵母反应的定量工具 细胞压力。 本项目建议书描述了数学的发展和应用 生物过程的细胞内现象建模工具， 开发分子水平的传感器，用于实时采集数据， 细胞生长和蛋白质表达。这些研究工具的效用 将在酵母中的未折叠蛋白质反应上进行评估 在单链抗体的表达期间，在酿酒酵母中表达。

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.