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GrgA:a Multifunctional Transcription Factor that Control Chlamydial Gene Expression

GrgA：控制衣原体基因表达的多功能转录因子

基本信息

批准号：
9884720
负责人：
HUIZHOU FAN
金额：
$ 23.73万
依托单位：
RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-04 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9884720
关键词：
Affinity Anti-Bacterial Agents Antibiotic Therapy Antibiotics Bacteria Bacterial RNA Binding Biology Catalytic Domain Cells ChIP-seq Chlamydia Chlamydia Infections Chlamydia genome Chlamydia trachomatis DNA DNA-Directed RNA Polymerase Defect Development Ectopic Pregnancy Environment Enzymes Escherichia coli Gene Expression Genes Genetic Transcription Genomics Goals Grant Growth Growth and Development function Heat-Shock Response High-Throughput DNA Sequencing Holoenzymes In Vitro Individual Infection Infertility Knock-out Length Medical Microbiology Pathogenicity Pelvic Inflammatory Disease Physiological Physiology Play Preventive Promoter Regions Proteins Publishing RNA Binding RNA chemical synthesis Reproductive system Research Role Scientist Sexual Transmission Sigma Factor Specificity Structure Testing Therapeutic Transcriptional Regulation Treatment Efficacy Woman Work abortion antimicrobial base biological adaptation to stress chromatin immunoprecipitation enzyme activity extracellular insight knockout gene medical attention mutant novel novel therapeutics overexpression pathogenic bacteria prevent promoter prophylactic response structural biology therapeutic target transcription factor transcriptome transcriptomics tubal infertility

项目摘要

PROJECT SUMMARY/ABSTRACT The goals of this R21 grant is to test the hypothesis that a novel Chlamydia-specific transcription factor termed GrgA controls chlamydial growth and/or development by functioning as a multifunctional protein in transcription. Chlamydia is an obligate intracellular bacterium with a unique developmental cycle. It is the number one sexually transmitted bacterial pathogen. Although mostly asymptomatic, chlamydial infection often leads to serious and long-lasting complications including (but not limited to) infertility, and pelvic inflammatory syndrome. Transcription controls chlamydial growth and pathogenicity, and is an effective therapeutic target for chlamydiae. However, current antichlamydials including transcription inhibition-based antichlamydials are not ideal therapeuticals because of their broad antibacterial spectrum. The novel transcription factor GrgA is found only in chlamydiae, and therefore represents a potentially novel and highly selective antichlamydial target. Our published work and unpublished preliminary studies suggest that GrgA plays multiple roles in transcription regulation. We propose two Specific Aims to test this hypothesis. In Aim 1, we will investigate the likelihood that GrgA facilitates assembly of chlamydial RNA polymerase. In Aim 2, we will exam the effects of GrgA gene knockout as well as GrgA overexpression on chlamydial growth, development and transcriptome expression. This research will yield insights into mechanisms that control transcription regulation in chlamydia, and may provide further rationale for targeting GrgA for therapeutic and prophylactic purposes.

项目总结/摘要这项R21基金的目的是检验一种新的衣原体特异性转录一种称为GrgA的因子通过作为一种多功能调节因子来控制衣原体的生长和/或发育，蛋白质转录。衣原体是一种专性细胞内细菌，具有独特的发育周期。它是头号性传播细菌病原体。虽然大多数无症状，衣原体感染通常导致严重和持久的并发症，包括（但不限于）不孕症，和盆腔炎综合征转录控制衣原体的生长和致病性，并且是一个重要的基因。衣原体感染有效治疗靶点。然而，目前的反衣原体包括转录基于抑制的抗衣原体药物由于其广谱抗菌性而不是理想的治疗剂。新的转录因子GrgA仅在衣原体中发现，因此代表了一种潜在的新的和高选择性的抗衣原体靶标。我们已发表的工作和未发表的初步研究表明， GrgA在转录调控中起着多种作用。我们提出两个具体目标来检验这一点假说.在目标1中，我们将研究GrgA促进衣原体RNA组装的可能性聚合酶。在目标2中，我们将检查GrgA基因敲除以及GrgA过表达对人乳腺癌细胞的影响。衣原体生长、发育和转录组表达。这项研究将有助于了解控制衣原体转录调节的机制，并可能为衣原体的基因表达提供进一步的理论基础。靶向GrgA用于治疗和预防目的。