Dr. Ming Tan is a physician scientist with a research interest in bacterial pathogenesis and infectious diseases. He is a faculty member in the Department of Microbiology and Molecular Genetics at the University of California, Irvine, which has a strong record of research in microbial pathogenesis and gene regulation. Dr. Tan is studying the bacterial pathogen, Chlamydia, which is the leading cause of sexually transmitted disease in the developed world and one of the main causes of preventable blindness in the developing world. In addition, Chlamydia has been associated with atherosclerotic heart disease. Dr. Tan's career goal is to maintain an independent research program that ultimately leads to new insights into chlamydial pathogenesis, and new therapeutic and preventative approaches towards chlamydial infections. ? ? Dr. Tan is investigating the intracellular survival and replication of Chlamydia, with a focus on the molecular mechanisms of chlamydial gene regulation. He is using an in vitro approach to study gene regulation, based on the transcription of cloned chlamydial promoters by purified RNA polymerase. In this proposal, several different mechanisms that regulate promoter activity will be investigated. A cis-acting DNA element has been identified in many chlamydial promoters and its presence increases promoter activity. Dr. Tan hypothesizes that a putative activator binds to this DNA element and upregulates transcription, providing a general switch for turning on chlamydial gene expression. This hypothesis will be tested by determining if the activity that is dependent on the DNA element is separable from the activity of RNA polymerase. Dr. Tan has also demonstrated that regulated chlamydial transcription can be reconstituted by adding recombinant chlamydial proteins to his in vitro assay. For example, heat shock promoters have been shown to be regulated by a transcriptional repressor. The mechanism by which increased temperature modulates the activity of this repressor, and leads to upregulation of heat shock gene expression, will be examined in this proposal. Additional forms of regulation will be studied by testing the activity of candidate transcription factors. Dr. Tan has reconstituted the activity of an alternative chlamydial RNA polymerase that transcribes specific genes by recognizing a different promoter structure. This reconstituted activity will be combined with a bioinformatics approach to identify genes that are regulated by this alternative RNA polymerase. ? ?
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