The work outlined in this study attempts to add clarification to the information processing and regulatory principles of biological organisms. The chemotactic response of bacteria is chosen as a model system for sensory transduction. The biochemical events involved in transmitting the signal processing it, and determining output response, will be studied at the molecular level. The procedures involve recombinant DNA methods and purification of the relevant proteins. One intensive study is devoted to the structure and function of the receptor since it is used as a model for transmembrane signaling and the understanding of conformational changes in proteins. Localized mutagenesis and physical studies including X-ray crystallography will be applied to the receptor to reveal the mechanism by which information is transmitted from the outside to the inside of the cell through a relatively small transmembrane region. To understand regulatory principles more extensively, the Krebs cycle and glyoxylate bypass will be studied intensively, particularly the role of phosphorylation at the crucial branchpoint. Studies in mutation to key enzymes, pseudorevertant selection, and overproduction and underproduction of enzymes in key pathways by recombinant DNA methods will be used to clarify the system. In particular, the energy cost of covalent modification and how the """"""""price'' affects the design will be investigated. The second phosphorylation system which will be under intensive investigation will be the protein kinase-C system of the neuroblastoma cell, which will be studied to clarify not only the principles of a second messenger system but also to understand specifically how it operates in the neurons of the brain. Although the above are parts of distinct systems and can be studied individually, a pattern of similar covalent modification, conformational changes and feedback properties should help in allowing each system to provide insight into the other. It is hoped that general principles of regulation and of information processing will be clarified.
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