Characterization of Enhancer Binding Proteins in Pseudomonas aeruginosa
铜绿假单胞菌增强子结合蛋白的表征
基本信息
- 批准号:9271431
- 负责人:
- 金额:$ 6.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-01 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:ADP Ribose TransferasesADP ribosylationAddressBacteriaBacterial ModelBehaviorBindingBinding ProteinsBioinformaticsBiologicalCell Adhesion MoleculesChronicDataDevelopmentEMSAElectrophoretic Mobility Shift AssayEnvironmentEnzymesExcisionGalactosidaseGene ExpressionGenesGeneticGenetic TranscriptionGoalsGrowthHandHealthHomologous GeneInfectionKnowledgeLaboratoriesLifeLungMeasuresMetabolicMetabolismMicrobial BiofilmsMissionModelingMulti-Drug ResistanceNatureNucleic Acid Regulatory SequencesNutritionalOperonOrganismOutcomePhenotypePhysiologicalPhysiologyProcessProcessed GenesProductionProgress ReportsProtein FamilyProteinsPseudomonas aeruginosaPublic HealthRNARegulationRegulonReporterResearchRoleSamplingSigma FactorSignal TransductionStagingStatistical Data InterpretationStressTechniquesTestingTranscriptional ActivationVirulenceVirulence FactorsVirulentWorkbaseburden of illnesscombatcystic fibrosis patientsdimethylargininaseenhancer binding proteininnovationinsightmembermutantnew therapeutic targetnovelnovel therapeutic interventionpathogenpathogenic bacteriapreventprotein functionquorum sensingresearch studytherapeutic developmenttranscription factortranscriptometranscriptome sequencingtranscriptomics
项目摘要
DESCRIPTION (provided by applicant)
There is a fundamental gap in understanding the role of transcription factors called enhancer binding proteins (EBPs) relate to virulence in the pathogenic bacterium, Pseudomonas aeruginosa. Continued existence of this gap represents an important problem because, until it is filled, understanding how and why EBPs regulate gene expression in P. aeruginosa will be largely incomprehensible. To address this, our long-term goal is to define the function(s) of several newly identified EBPs in the global physiology of P. aeruginosa. Specifically, it is imperative to know what genes and operons are regulated by these EBPs, and what signals the EBPs respond to in order to activate transcription. The overall objective of this application will e to define the regulons of EBPs in the medically relevant bacterial strain, P. aeruginosa, and determine their roles in metabolism and virulence factor production. The central hypothesis is that EBP transcription factors will be responsible for regulating a diverse set of metabolisms and virulence factor production in P. aeruginosa. The hypothesis is based on our own preliminary findings, which were generated by examining physiological and transcriptomic data for wild type P. aeruginosa PAO1 and a P. aeruginosa EBP deletion strains generated in our laboratory. The rationale for the proposed research is that knowledge of the genetic networks regulated by EBPs will generate new strategies to prevent the expression of virulence factors or to inhibit the general metabolism of P. aeruginosa and thereby restrict its ability to cause infection. Guided by strong preliminary data, the hypothesis will be tested by pursuing two specific aims: 1) Characterization of PA1196, a protein proposed to regulate expression of PA1195 which encodes a dimethylarginine dimethylaminohydrolase that can degrade toxic methylarginines in P. aeruginosa and 2) Identifying the functions of uncharacterized EBPs. Under the first aim, techniques, which have been established as feasible in the applicant's hands, will be used A) to measure expression levels of the PA1195 gene which is downstream of the putative regulator, PA1196; B) evaluate the binding of the PA1196 protein to 5' regulatory regions of PA1196 by EMSA; and C). Biochemically characterize the PA1197 protein. Under the second aim we will use transcriptomics and deletion strategies to identify the functions of the five remaining uncharacterized EBPs of P. aeruginosa. The approach is innovative because it identifies and characterizes all of the EBPs of P. aeruginosa, a model bacterial pathogen. The proposed research is significant, because it is expected to vertically advance and expand understanding of EBPs regulate metabolism and virulence factor production in P. aeruginosa. Ultimately, such knowledge has the potential to identify new therapeutic targets to interfere with virulence factor production in P. aeruginosa.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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CHRISTOPHER T NOMURA其他文献
CHRISTOPHER T NOMURA的其他文献
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{{ truncateString('CHRISTOPHER T NOMURA', 18)}}的其他基金
Characterization of a New Key Regulator for Phenazine Production in Pseudomonads
假单胞菌吩嗪生产的新型关键调节剂的表征
- 批准号:
8573775 - 财政年份:2013
- 资助金额:
$ 6.77万 - 项目类别:
Characterization of a New Key Regulator for Phenazine Production in Pseudomonads
假单胞菌吩嗪生产的新型关键调节剂的表征
- 批准号:
8903309 - 财政年份:2013
- 资助金额:
$ 6.77万 - 项目类别:
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