Molecular mechanisms of gene regulation in Chlamydia

简介（由申请人提供）：谭明博士是一名内科科学家，主要研究方向是细菌发病机制和传染病。他是加州大学欧文分校微生物学和分子遗传学系的一名教员，在微生物发病机制和基因调控方面有很强的研究记录。谭博士正在研究衣原体这种细菌病原体，它是发达国家性传播疾病的主要原因，也是发展中国家可预防性失明的主要原因之一。此外，衣原体与动脉粥样硬化性心脏病有关。Tan博士的职业目标是保持一个独立的研究项目，最终导致对衣原体发病机制的新见解，以及对衣原体感染的新治疗和预防方法。

DESCRIPTION (provided by applicant): 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.