ABSTRACT WSU / UI - Genetic regulation of developmental transitions in Chlamydia Bacteria of the genus Chlamydia include the significant human pathogens C. trachomatis, a leading cause of sexually transmitted infections, and C. pneumonia, a cause of significant respiratory disease. All chlamydiae are obligate intracellular parasites that depend on infection of a host cell to undergo a bi-phasic developmental cycle. Following host cell invasion by the infectious Elementary Body (EB), transition to the replicative but non- infectious Reticulate Body (RB) is essential for propagation. Differentiation of the RB back to the EB is essential to generate infectious progeny. The EB form has historically been regarded as metabolically inert. However, recent data suggest that EBs can respond to specific molecular signals, including glucose 6- phosphate and ATP that are predicted to be present at mucosal surfaces. The ability of EBs to respond to specific nutrients is consistent with their ability to respond actively to cues in their environment even before internalization into a host cell. Via analysis of EB pre-invasion molecular events (e.g., transcription, and maintenance of infectivity over time) and mathematical modeling, this project is aimed at determining the role of active EB metabolic responses during initial interactions with mucosal surfaces, and identification of gene regulatory events that control chlamydial morphological differentiation.