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Elucidating the Sensing Abilities of Virulence Regulatory Systems

阐明毒力调节系统的感知能力

基本信息

批准号：
10452800
负责人：
Eduardo Groisman
金额：
$ 53.99万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-05 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10452800
关键词：
Algorithms Anti-Bacterial Agents Antibiotics Antimicrobial Resistance Bacteria Bacterial Drug Resistance Bacterial Physiology Binding Binding Proteins Binding Sites Biochemical Biological Cell physiology Cells ChIP-seq Code DNA DNA Sequence Disease Ensure Enzymes Equilibrium Evaluation Fluorescence Gastroenteritis Gene Activation Genes Genetic Genetic Transcription Genome Grant Histones Human Infection Life Style Measures Mediating Messenger RNA Methodology Methods Molecular Molecular Chaperones Mus Open Reading Frames Pathogenesis Physiological Post-Transcriptional Regulation Process Promoter Regions Property Proteins Proteome RNA RNA Binding RNA-Binding Proteins Research Role Salmonella Salmonella typhimurium Signal Transduction Site Stress Structural Protein Superhelical DNA System Tissues Transcription Coactivator Transcription Initiation Typhoid Fever Virulence Virulence Factors antimicrobial drug cell envelope experience genome-wide in vivo macrophage microorganism novel pathogen pathogenic bacteria programs response sensor success transcription factor transmission process

项目摘要

PROJECT SUMMARY Bacterial pathogens exert tight control over their proteomes. This proposal examines how Salmonella enterica serovar Typhimurium exerts this control. It makes direct use of novel methods and conceptual breakthroughs developed during the last grant period. First, we will identify genes that govern global DNA supercoiling using Fluorescence Evaluation of DNA Supercoiling, a novel high throughput method that examines DNA supercoiling in living cells. We will then investigate how the identified genes control this essential process. Second, we will explore the mechanism by which the master virulence regulator PhoP promotes transcription of an open reading frame when binding to that very same open reading frame. These unusually located PhoP binding sites were uncovered with Identification of Transcription Factor Sites, a novel algorithm that captures transcription factor binding sites genome wide and overcomes the limitations of SELEX and ChIP-seq. And third, we will determine the post- transcriptional mechanisms by which the RNA chaperone CspC and the novel small protein UgtS control the abundance and activity of the virulence protein UgtL. The proposed research will provide a molecular understanding of cellular physiology and likely be broadly applicable because all bacteria supercoil their DNA, activate gene transcription, and exert post-transcriptional control of their genes.

项目摘要细菌病原体对其蛋白质组施加严格控制。该提案审查了鼠伤寒沙门氏菌如何发挥这种控制作用。它直接利用了在上一个赠款期间开发的新方法和概念突破。首先，我们将使用荧光技术鉴定控制全局DNA超螺旋的基因。 DNA超螺旋的评价，一种新的高通量检测DNA的方法活细胞中的超螺旋。然后，我们将研究所确定的基因如何控制这个重要的过程。第二，我们将探讨机制，毒力调节因子PhoP促进开放阅读框的转录，绑定到同一个开放的阅读框架。这些异常定位的PhoP绑定用一种新的算法--转录因子位点识别法发现了一些位点它能在全基因组范围内捕获转录因子结合位点， SELEX和ChIP-seq的局限性。第三，我们将确定后- RNA伴侣CspC和新的小分子的转录机制，蛋白UgtS控制毒力蛋白UgtL的丰度和活性。的拟议的研究将提供细胞生理学的分子理解，因为所有细菌都会超螺旋它们的DNA，激活基因转录，并发挥其基因的转录后控制。