Physical Chemical Basis of Control of Gene Expression

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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.