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
基本信息
- 批准号:9274236
- 负责人:
- 金额:$ 67.34万
- 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 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAlveolar Bone LossAnimal ModelApoptosisAutomobile DrivingBehaviorBindingBinding ProteinsBiochemicalBiological AssayBiologyCalciumCell CommunicationCell Culture TechniquesCell Differentiation processCell physiologyCell surfaceCellsChronicCleaved cellComplexCytopathologyDiseaseEnvironmentExtracellular MatrixFibronectinsGelatinase AGenerationsGeneticGingivaGingival Crevicular FluidGoalsHomeostasisHumanImmune responseIndividualInfectionInflammationInflammatoryKnowledgeLeadLesionLipoproteinsMediatingMediator of activation proteinMembraneMembrane ProteinsMolecular AnalysisMolecular BiologyMonitorMutationNatural ImmunityNutrientOralOrder SpirochaetalesOrganismParentsPathway interactionsPatternPenetrationPeptide HydrolasesPeriodontal DiseasesPeriodontal LigamentPeriodontitisPorphyromonas gingivalisPositioning AttributeProcessProteinsRecombinant ProteinsResearchRoleSignal TransductionSurfaceTestingTissuesTooth SocketTooth structureTreponemaTreponema denticolaacquired immunityalveolar bonecytotoxicdentilisinexperiencegenetic analysisgenetic manipulationhost-microbe interactionsimmunoregulationin vivoinhibitor/antagonistinsightinterestmembermicrobiomemigrationmutantoral pathogenoral spirochetesosteoblast differentiationproMMP-2protein complexprotein expressionprotein protein interactionpublic health relevanceresponsetherapeutic target
项目摘要
DESCRIPTION (provided by applicant): The goal of this research is to characterize the role of Treponema denticola (Td) surface proteins in interaction of this human oral spirochete with host tissue, thereby gaining insight into mechanisms by which these organisms contribute to initiation and progression of periodontal disease. We focus on analysis of Td 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 Td cytopathic behavior in periodontal disease. To characterize their specific roles in microbe-host interactions, our approach is to utilize purified native and recombinant proteins as well as isogenic Td strains carrying defined mutations in individual components of these outer membrane complexes. We will first extend our ongoing studies characterizing dentilisin assembly in the Td outer membrane. Then, to further studies of host cell responses to Td challenge, we will (A) determine the mechanism of dentilisin-induced activation of pro-MMP-2 and (B) characterize MMP-2-dependent fibronectin fragmentation resulting from Td challenge of PDL cells. This project will test the hypothesis that dentilisin is an effector protein whose activity results in magnified "downstream" signaling effects that are likely to be significant in vivo. 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.
描述(由申请人提供):本研究的目的是表征齿垢密螺旋体(Td)表面蛋白在该人类口腔螺旋体与宿主组织相互作用中的作用,从而深入了解这些生物体导致牙周病发生和进展的机制。我们专注于分析Td蛋白复合物,直接影响细胞分离的组织,包括牙周膜(PDL),包括牙齿和牙槽骨之间的连接的牙槽窝:特别是PrtP脂蛋白蛋白酶复合物(牙本质)和寡聚Msp蛋白。我们的总体假设是牙本质素和Msp是牙周病中Td细胞病变行为的主要贡献者。为了表征它们在微生物-宿主相互作用中的特定作用,我们的方法是利用纯化的天然和重组蛋白以及在这些外膜复合物的各个组分中携带定义突变的等基因Td菌株。我们将首先扩展我们正在进行的研究表征牙本质素组装在Td外膜。然后,为了进一步研究宿主细胞对Td攻击的反应,我们将(A)确定牙本质素诱导的pro-MMP-2活化的机制和(B)表征PDL细胞的Td攻击导致的MMP-2依赖性纤连蛋白片段化。这个项目将测试的假设,牙本质是一种效应蛋白,其活动的结果放大的“下游”信号的影响,可能是显着的体内。我们的研究团队在螺旋体分子生物学、细胞外基质生物学和炎症性疾病的细胞病理学方面拥有独特的专业知识,能够进行这些研究。本计画的完成将有助于螺旋体分子生物学的基础知识,以及了解慢性感染如牙周疾病中微生物与宿主的相互作用。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
J CHRISTOPHER FENNO其他文献
J CHRISTOPHER FENNO的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
$ 67.34万 - 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:
$ 67.34万 - 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:
10366859 - 财政年份:2015
- 资助金额:
$ 67.34万 - 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:
$ 67.34万 - 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:
$ 67.34万 - 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:
$ 67.34万 - 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:
$ 67.34万 - 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:
$ 67.34万 - 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:
$ 67.34万 - 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:
$ 67.34万 - 项目类别:
相似海外基金
G13 signaling attenuates periodontal inflammation and alveolar bone loss in the mouse model of age-associated periodontitis
G13 信号传导可减轻年龄相关性牙周炎小鼠模型中的牙周炎症和牙槽骨丢失
- 批准号:
10404267 - 财政年份:2021
- 资助金额:
$ 67.34万 - 项目类别:
G13 signaling attenuates periodontal inflammation and alveolar bone loss in the mouse model of age-associated periodontitis
G13 信号传导可减轻年龄相关性牙周炎小鼠模型中的牙周炎症和牙槽骨丢失
- 批准号:
10444932 - 财政年份:2021
- 资助金额:
$ 67.34万 - 项目类别:
Identification of the causative gene of pathological alveolar bone loss and its gene polymorphism
病理性牙槽骨丢失致病基因的鉴定及其基因多态性
- 批准号:
17H06884 - 财政年份:2017
- 资助金额:
$ 67.34万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Oral immune activation and alveolar bone loss in HIV-infected postmenopausal women
感染艾滋病毒的绝经后妇女的口腔免疫激活和牙槽骨丢失
- 批准号:
9320344 - 财政年份:2017
- 资助金额:
$ 67.34万 - 项目类别:
Do Exosomes play a role in Alveolar Bone Loss in Periodontal Disease?
外泌体在牙周病牙槽骨丢失中发挥作用吗?
- 批准号:
17K11682 - 财政年份:2017
- 资助金额:
$ 67.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Oral commensal flora accelerates age-related alveolar bone loss in mice
口腔共生菌群加速小鼠年龄相关的牙槽骨流失
- 批准号:
26893304 - 财政年份:2014
- 资助金额:
$ 67.34万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Are microRNAs in Exosomes Involved in Alveolar Bone Loss in Periodontal Disease?
外泌体中的 microRNA 是否与牙周病中的牙槽骨丢失有关?
- 批准号:
26462853 - 财政年份:2014
- 资助金额:
$ 67.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A basic research aimed to develop nevel preventive and therapeutic measures for alveolar bone loss in periodontitis
牙周炎牙槽骨丢失新防治措施的基础研究
- 批准号:
25893241 - 财政年份:2013
- 资助金额:
$ 67.34万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
A control of tooth movement by sympathetic nervous system and development of anti-drug for alveolar bone loss
交感神经系统对牙齿移动的控制及抗牙槽骨丢失药物的开发
- 批准号:
25870861 - 财政年份:2013
- 资助金额:
$ 67.34万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Identifying Novel Markers of Alveolar Bone loss: Developing New Diagnostic Approaches for the Most Prevalent Forms of Bone Loss
识别牙槽骨丢失的新标志物:为最常见的骨丢失形式开发新的诊断方法
- 批准号:
252974 - 财政年份:2012
- 资助金额:
$ 67.34万 - 项目类别:
Operating Grants