Research Project
6701892
DESCRIPTION (provided by applicant): Extracellular communication among bacteria involves a rich diversity of signaling molecules, signal reception and transduction systems. The exchange of diffusible signaling molecules between prokaryotes is important in a variety of physiological processes including development, pathogenicity, biofilm formation and competence. The proposed research program is designed to explore the structure and function of extracellular signaling molecules involved in the morphological differentiation of the filamentous microbe Streptomyces coelicolor. S. coelicolor is a model streptomycete; this genus is responsible for the production of approximately 70% of the antibiotics currently prescribed, as well antihelminthic and immunosuppressive agents and drugs with antineoplastic activity. The exchange of signaling molecules among S. coelicolor cells is evidenced by the complete rescue of development when two S. coelicolor bald (bld) mutants blocked in morphogenesis are plated near one another. Based on the pattern of complementation when bld mutants are plated in pair wise combination, it is hypothesized that a hierarchical signaling cascade occurs such that each bld gene is involved directly or indirectly in the synthesis, perception of, or response to one of six different extracellular signaling molecules. Each signal then induces the production of the next, ultimately leading to synthesis of the structural morphogen, SapB. The specific aims of the proposed research are to purify and resolve the structure of three of these bld-derived signaling molecules. Purified signals will then be used to probe the role of these molecules in initiating morphological differentiation. Antibodies will be prepared too so that the spatial, temporal and genetic regulation of signal production can be evaluated and microarray analysis will be performed to identify genes whose expression responds to the presence of the extracellular signals. Finally, as an Academic Research Enhancement Award (AREA) proposal, the program of proposed research will serve to train undergraduate and Master's level students in the design and execution of experiments in the life sciences.
