Treponema - Host Cell and Tissue Interactions
密螺旋体 - 宿主细胞和组织的相互作用
基本信息
- 批准号:10366859
- 负责人:
- 金额:$ 61.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-01 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAlveolar Bone LossAnimal ModelBehaviorBindingBiochemicalBiological AssayBiologyCalciumCell modelCellsChronicComplexComplex AnalysisCytopathologyCytoskeletonDataDiseaseDisease ProgressionEnvironmentEventExtracellular MatrixFibronectinsGelatinase AGenerationsGeneticGoalsHealth TransitionHomeostasisHumanImmune responseIndividualInflammatoryIntegration Host FactorsIntegrinsIntercellular JunctionsKnowledgeLesionLipoproteinsMaintenanceMatrix MetalloproteinasesMediatingMediator of activation proteinMembraneMembrane ProteinsMetabolicMolecular AnalysisMolecular BiologyMouth DiseasesMutationNisinOralOrder SpirochaetalesPTK2 geneParentsPathway interactionsPenetrationPeptide HydrolasesPeriodontal DiseasesPeriodontal LigamentPeriodontitisPhosphorylcholinePositioning AttributeProteinsRecombinant ProteinsResearchRoleSignal TransductionSurfaceTLR2 geneTestingTissuesTooth SocketTooth structureTreponemaTreponema denticolaVDAC1 genealveolar boneantimicrobial peptidebacteriocinchronic infectioncytotoxicdentilisindysbiosisexperiencegenetic analysisgenetic manipulationhost-microbe interactionsimmunoregulationin vivoinsightinterestintermolecular interactionlipooligosaccharidemouse modelmutantoral spirochetesosteoblast differentiationpathobiontprotein complexprotein protein interactionresponsesystemic inflammatory responsetherapeutic target
项目摘要
ABSTRACT
The goal of this research is to characterize the role of Treponema denticola surface proteins in interaction of
this human oral spirochete with host tissue, thereby gaining insight into mechanisms by which T. denticola
contributes to initiation and progression of periodontal disease. We focus on analysis of T. denticola protein
complexes that directly affect cells isolated from tissue comprising the periodontal ligament (PDL) that
comprises the junction between the tooth and the alveolar bone of the tooth socket: specifically the PrtP
lipoprotein protease complex (dentilisin) and the oligomeric Msp protein. Our overall hypothesis is that
dentilisin and Msp are major contributors to T. denticola cytopathic behavior in periodontal disease, In this
context we will examine specific domains of dentilisin and Msp, as well as the T. denticola lipooligosaccharide
component of the outer membrane. To characterize their specific roles in microbe-host interactions, our
approach is to utilize purified native and recombinant proteins as well as isogenic T. denticola strains carrying
defined mutations in individual components of these outer membrane complexes. We will first extend our
ongoing studies characterizing dentilisin and Msp assembly in the Td outer membrane. Then, to further studies
of host responses to challenge by Td and its specific components, we will then characterize in a cell model T.
denticola-induced dysregulation of TLR/MyD88 and Integrin/FAK signaling mechanisms and consequences for
the cytoskeleton as well as expression and activity of matrix metalloproteinases. We will determine the extent
to and the mechanisms by which specific T. denticola components contribute to tissue destruction in a mouse
model of periodontal disease. Finally, we will test the ability of the the antimicrobial peptide nisin to modulate T.
denticola-induced dysbiotic signaling in both the cell and animal models. Our research team is uniquely
positioned to conduct these studies, with combined expertise in spirochete molecular biology, extracellular
matrix biology and cytopathology of inflammatory diseases. Completion of this project will contribute to both
basic knowledge of spirochete molecular biology and to understanding of microbe-host interactions in chronic
infections such as periodontal diseases.
摘要
本研究的目的是描述齿垢密螺旋体表面蛋白在与细胞相互作用中的作用。
这种人类口腔螺旋体与宿主组织,从而获得深入了解的机制,T。齿垢密
导致牙周病的发生和发展。重点分析了T.齿垢蛋白
直接影响从包含牙周膜(PDL)的组织分离的细胞的复合物,
包括牙齿和牙槽骨之间的连接处:具体地,
脂蛋白蛋白酶复合物(牙本质素)和寡聚Msp蛋白。我们的总体假设是
牙本质素和Msp是T.牙周病的细胞病变行为,在这方面,
在上下文中,我们将检查牙本质蛋白和Msp的特定结构域,以及T.齿垢脂寡糖
外膜的组成部分。为了描述它们在微生物-宿主相互作用中的特定作用,我们
方法是利用纯化的天然和重组蛋白以及同基因T。携带
在这些外膜复合物的单个组分中定义突变。我们将首先扩展我们的
正在进行的表征Td外膜中牙本质蛋白和Msp组装的研究。然后,为了进一步研究
宿主对Td及其特定组分攻击的反应,然后我们将在细胞模型T中表征。
齿状突诱导的TLR/MyD 88和整合素/FAK信号转导机制的失调及其后果
细胞骨架以及基质金属蛋白酶的表达和活性。我们将确定
以及特异性T.齿垢成分导致小鼠组织破坏
牙周病模型。最后,我们将测试抗菌肽nisin调节T.
在细胞和动物模型中,denticola诱导的生态失调信号。我们的研究团队是独一无二的
定位进行这些研究,结合螺旋体分子生物学,细胞外
炎症性疾病的基质生物学和细胞病理学该项目的完成将有助于
螺旋体分子生物学的基本知识,以及对慢性疾病中微生物-宿主相互作用的理解
牙周病等感染。
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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J CHRISTOPHER FENNO其他文献
J CHRISTOPHER FENNO的其他文献
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{{ truncateString('J CHRISTOPHER FENNO', 18)}}的其他基金
Oral Treponema Surface Proteins: Host Cell Interactions
口服密螺旋体表面蛋白:宿主细胞相互作用
- 批准号:
9096755 - 财政年份:2015
- 资助金额:
$ 61.88万 - 项目类别:
Oral Treponema Surface Proteins: Host Cell Interactions
口服密螺旋体表面蛋白:宿主细胞相互作用
- 批准号:
8941164 - 财政年份:2015
- 资助金额:
$ 61.88万 - 项目类别:
Treponema - Host Cell and Tissue Interactions
密螺旋体 - 宿主细胞和组织的相互作用
- 批准号:
10551350 - 财政年份:2015
- 资助金额:
$ 61.88万 - 项目类别:
Oral Treponema Surface Proteins: Host Cell Interactions
口服密螺旋体表面蛋白:宿主细胞相互作用
- 批准号:
9274236 - 财政年份:2015
- 资助金额:
$ 61.88万 - 项目类别:
Treponomics: enhanced tools for genetic manipulation in spirochetes
密螺旋体组学:螺旋体基因操作的增强工具
- 批准号:
8489671 - 财政年份:2013
- 资助金额:
$ 61.88万 - 项目类别:
Treponomics: enhanced tools for genetic manipulation in spirochetes
密螺旋体组学:螺旋体基因操作的增强工具
- 批准号:
8719805 - 财政年份:2013
- 资助金额:
$ 61.88万 - 项目类别:
Surface protein complexes of oral treponemes: assembly and host cell interactions
口腔密螺旋体的表面蛋白复合物:组装和宿主细胞相互作用
- 批准号:
7826782 - 财政年份:2009
- 资助金额:
$ 61.88万 - 项目类别:
Surface protein complexes of oral treponemes: assembly and host cell interactions
口腔密螺旋体的表面蛋白复合物:组装和宿主细胞相互作用
- 批准号:
7464047 - 财政年份:2009
- 资助金额:
$ 61.88万 - 项目类别:
Choline phosphotransferase-dependent phospholipid synthesis in Treponema
密螺旋体中胆碱磷酸转移酶依赖性磷脂合成
- 批准号:
7509591 - 财政年份:2008
- 资助金额:
$ 61.88万 - 项目类别:
Choline phosphotransferase-dependent phospholipid synthesis in Treponema
密螺旋体中胆碱磷酸转移酶依赖性磷脂合成
- 批准号:
7640752 - 财政年份:2008
- 资助金额:
$ 61.88万 - 项目类别:
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