Physical Chemical Basis of Control of Gene Expression

这个项目在化学特别项目办公室的生命过程化学倡议中。这项研究的目的是了解在生命系统中控制基因表达的物理化学基础。调控蛋白质和核酸稳定性和特异性的一般热力学原理，以及涉及这些大分子物种结合和解离的重要步骤，现在在实验室条件下的稀溶液中得到了合理的理解。这个项目将把这种水平的化学理解扩展到细胞质拥挤的环境中。这项基础性研究将具有生物医学和生物技术意义。实验将量化a)大肠杆菌细胞质的化学环境及其变异性，b)该环境中DNA的性质和结构，c)细胞质环境对蛋白质和核酸非共价相互作用的影响。特别是，该项目将解决体内-体外悖论的起源，在这种悖论中，蛋白质-DNA相互作用在体外高度依赖盐，在体内不依赖盐。这个项目是对基金会以前支持的项目的更新。

This project is in the Chemistry of Life Processes Initiative in the Office of Special Projects in Chemistry. The objectives of this research are to understand the physical chemical foundations of control of gene expression in living systems. The general thermodynamic principles governing stability and specificity of regulatory proteins and nucleic acids, and the important steps involved in the association and dissociation of these macromolecular species, are now reasonably understood in dilute solution under laboratory conditions. This project will extend the this level of chemical understanding to the crowded environment of the cell cytoplasm. This fundamental research will have biomedical and biotechnological significance. Experiments will quantify a) the chemical environment of the cytoplasm of E. coli and the variability of this environment, b) the properties of and structures of DNA in this environment, and c) the effects of the cytoplasmic environment on noncovalent interactions of proteins and nucleic acids. In particular the project wil address the origins of the in vivo-in vitro paradox in which protein-DNA interactions are highly salt dependent in vitro and salt independent in vivo. This project is a renewal of one previously supported by the Foundation.