Mapping Protein Interaction Networks Essential for Gonococcal Pathogenesis
绘制淋球菌发病机制所必需的蛋白质相互作用网络
基本信息
- 批准号:10814526
- 负责人:
- 金额:$ 59.46万
- 依托单位:
- 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:2021-05-06 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAnimal ModelAntibiotic ResistanceAntibioticsArchitectureAutomobile DrivingAwarenessBacteriaBiologicalBiological AssayBiologyBiomedical ResearchCell AdhesionCellsClinicalCommunicable DiseasesCommunitiesComparative Genomic AnalysisComputer ModelsDependenceDevelopmentDiseaseDrug resistanceEnvironmentEscherichia coliEtiologyFemale genitaliaFoundationsFutureGene Expression ProfilingGenerationsGenetic ScreeningGenitalGenitaliaGenomeGenomic approachGenomicsGoalsGonorrheaGrantGrowthHealthHost resistanceHumanImmune EvasionIn VitroIncidenceInfectionInterdisciplinary StudyInterventionInvadedInvestigationKnowledgeKnowledge acquisitionLabelLifeMale Genital OrgansMapsMass Spectrum AnalysisMediatingMetabolicMetabolismMethodsMicrobeModelingMolecularMorbidity - disease rateMucous MembraneMutagenesisNeisseria gonorrhoeaeNutrientOutcomePathogenesisPathologicPathway AnalysisPhenotypePhysiologicalPhysiologyPopulationProcessProteinsProteomeProteomicsRecording of previous eventsResistanceResistance to infectionResourcesRoleSexually Transmitted AgentsSexually Transmitted DiseasesStressSuperbugSystemSystems BiologyTechnologyTherapeuticTherapeutic InterventionTransgenic MiceValidationVariantWorkchronic infectionclinically relevantcombatcommensal bacteriacomparativecomparative genomicsdrug developmentdrug discoveryexperimental studyfitnessfollow-upfrailtygene complementationhuman pathogenhumanized mouseimprovedin vivoinnovationinsightmacromoleculemicrobiomemouse modelpathogenpharmacologicprotein complexprotein protein interactionreproductive tractresearch studyresistant straintrendvalidation studies
项目摘要
Neisseria gonorrhoeae (Ngo) is the etiological agent of the sexually transmitted infection (STI) gonorrhea, a high
morbidity disease with ~100 million cases worldwide each year. Alarmingly, therapeutic and pharmacologic
approaches to treat gonorrhea are under threat by the global emergence of `superbug' strains resistant to all
clinically useful antibiotics. Gonococci are exquisitely adapted to life in humans, to the extent that they have shed
much of the metabolic capacity typical of other bacteria and depend upon unique strategies that allow for
replication and immune evasion while colonizing human mucosal tissues. Reflecting this specialization, Ngo
genomes encode less than half the number of proteins observed in more prototypical bacteria such as E. coli. A
biological enigma then is how the neisserial genome has evolved to exploit a variety of mucosal niches and how
strain variation contributes to pathogenesis. Our hypothesis is that this depends on specialized protein-protein
interaction networks, and that acquiring this knowledge will have major clinical value because it would reveal
protein complexes and processes uniquely required by gonococci but not commensal species, either because
they have distinct functional capabilities or because the smaller neisserial genome lacks functional redundancy
that allow other bacteria to overcome environmental or other stresses. The core goal of our multidisciplinary
research strategy is the generation of global protein interaction networks of gonococci that offer a detailed
systems-based understanding of the specialized cellular apparatus used by Ngo during infection. While
population genomic, transcriptional profiling and genetic screens have provided valuable insights into Ngo
biology, these studies would gain significant benefit through their integration with comprehensive roadmaps
detailing the organization of protein complexes that support growth and infection phenotypes. Key to the clinical
relevance of this project is a focus on the impact of strain variation through investigations of infectious clinical
isolates of Ngo, supported by complementary investigations of the population genomics of Ngo. We will combine
quantitative mass spectrometry, network analysis, comparative genomics and targeted mutagenesis with in vitro
and in vivo phenotype analysis to illuminate macromolecular protein assemblies that are critical to infection and
clinical persistence within the genital mucosa. By the end of this grant, we will have identified key conserved
components of the physical circuitry driving gonococcal growth, infection and adaptation to human mucosal
tissues, providing mechanistic insights into its unique pathobiology, and laying the foundation for future clinical
intervention strategies to combat infectious disease.
淋病奈瑟菌(Neisseria gonorrhoeae, Ngo)是性传播感染(STI)淋病的病原,发病率高
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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Andrew EMILI其他文献
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{{ truncateString('Andrew EMILI', 18)}}的其他基金
Identification and characterization of the CD31-ApoE-mCRP pathway for Alzheimer's disease in humans.
人类阿尔茨海默病 CD31-ApoE-mCRP 通路的鉴定和表征。
- 批准号:
10591027 - 财政年份:2022
- 资助金额:
$ 59.46万 - 项目类别:
Mapping Protein Interaction Networks Essential for Gonococcal Pathogenesis
绘制淋球菌发病机制所必需的蛋白质相互作用网络
- 批准号:
10401945 - 财政年份:2021
- 资助金额:
$ 59.46万 - 项目类别:
Genetic Modifiers of Protein Interaction Networks in Tauopathy
Tau 病中蛋白质相互作用网络的遗传修饰
- 批准号:
10386807 - 财政年份:2019
- 资助金额:
$ 59.46万 - 项目类别:
Genetic Modifiers of Protein Interaction Networks in Tauopathy
Tau 病中蛋白质相互作用网络的遗传修饰
- 批准号:
10654526 - 财政年份:2019
- 资助金额:
$ 59.46万 - 项目类别:
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