The Regulation of gene expression in Chlamydia

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DESCRIPTION (provided by applicant): Chlamydia is the leading cause of sexually transmitted disease in the developed world, and preventable blindness in the developing world. Our long-term goal is to define the molecular mechanisms that regulate chlamydial gene expression so that we may intervene during the organism's intracellular developmental cycle. Our central hypothesis is that chlamydial gene expression is coordinately regulated at the transcriptional level by master regulatory molecules, such as activators and repressors, and by alternative forms of RNA polymerase. We propose three aims: 1) Investigate the function of a cis-acting DNA element that is important for Chlamydia-specific promoter activity. We will use biochemical and physical approaches to determine if a novel DNA element called the Spacer A/T region exerts its positive effect on transcription by binding an activator. 2) Define the role of HrcA, a transcription factor that regulates the expression of heat shock genes. We will determine how heat shock gene expression is regulated by the physical state of the HrcA repressor, higher temperature, DNA topology, and by the heat shock protein, GroEL. 3) Define the role of sigma28 RNA polymerase, an alternative RNA polymerase. We will use functional, bioinformatics and DNA microarray approaches to identify sigma28 promoters and sigma28-regulated genes.