Retooling innate immunity: An investigation of TLR-mediated glial priming across lifespan
重组先天免疫:跨生命周期 TLR 介导的神经胶质启动的研究
基本信息
- 批准号:10533785
- 负责人:
- 金额:$ 40.25万
- 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:2021-01-01 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAffinityApoptosisApoptoticAutomobile DrivingCellsClinicalCommunicationCompetenceConsumptionDevelopmentDiseaseDrosophila genusEarly DiagnosisEmbryoEnsureExcisionFoundationsHumanInflammationInnate Immune SystemInvestigationLigandsLinkLongevityMAP Kinase GeneMaintenanceMediatingMental disordersModelingMolecularNatural ImmunityNecrosisNervous SystemNeuritesNeurodevelopmental DisorderNeurogliaNeuronsOlfactory PathwaysPathway interactionsPatternPhagocytesPhagocytosisPhenotypePlayPopulationPresynaptic TerminalsProcessPublishingReceptor SignalingResearchRoleRuptureShapesSignal PathwaySignal TransductionSpecificitySpeedStereotypingSupport SystemSynapsesSystemTXN geneTestingToll-Like Receptor PathwayToll-like receptorsWorkaxon guidanceaxon injurybrain healthdensitydetection platformflyin vivo Modelinsightinterestneural circuitneurodevelopmentneuron lossneurotransmissionnovelpresynapticpreventreceptorspatiotemporalsuccesssynaptic functionsynaptogenesistoolvirtual
项目摘要
This proposal examines how a novel TLR glial signaling pathway drives phagocytic competence in
glia, and defines its function in pruning neuronal number and connectivity across lifespan. Glia
provide an extensive support system for healthy neurons by promoting their survival, connectivity,
and synaptic function. Remarkably, glia can rapidly switch roles to precisely eliminate dying neurons
or unwanted neurites/synapses by phagocytosis. These diametrically opposed functions necessitate
fail-safe signaling mechanisms between neurons and glia; yet hese crucial regulatory mechanisms
have remained largely obscure. Toll-like receptor (TLR) pathways were first identified for their roles in
embryonic patterning and have since been defined as a conserved centerpiece of innate immunity.
Our lab made the unexpected discovery that one of the most pronounced phenotypes associated with
loss of a Drosophila TLR, a dramatic increase in the number of apoptotic neurons during
development, is caused by selective loss of the TLR in glia. We demonstrated that release of the TLR
ligand from dying neurons activates a novel TLR pathway in glia to drive phagocytic competence.
In this proposal we build on our novel preliminary findings to establish how this pathway regulates the
speed and specificity of debris clearance, and define its roles in neuron-glia interactions in synapse,
neurite, and neuron removal across lifespan. Our unifying hypothesis is that non-canonical TLR
signaling underlies the speed and specificity of debris clearance critical for proper CNS development
and function. In the first aim, we focus on elucidating how glia are transformed into phagocytes during
development by defining how information is relayed through the TLR pathway to elucidate how glia
are primed to become phagocytic. In the second aim, we seek to extend our published work to
investigate whether TLR signaling is a widespread early detection system to alert glia to the presence
of neuronal debris. And in the third aim, we examine the function of TLR signaling in sculpting circuits
in the olfactory system based on our preliminary findings that glial TLR signaling constrains synapse
number in this well defined circuit. Here we propose to leverage the fly olfactory circuit as a model for
defining glial phagocytic function in synapse maintenance. Together, these studies will shed critical
light on the early signaling interactions between glia and their phagocytic substrates essential for
brain health across lifespan.
本研究探讨了一种新的TLR胶质信号通路如何驱动细胞吞噬能力
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 }}
Heather Broihier其他文献
Heather Broihier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('Heather Broihier', 18)}}的其他基金
Retooling innate immunity: An investigation of TLR-mediated glial priming across lifespan
重组先天免疫:跨生命周期 TLR 介导的神经胶质启动的研究
- 批准号:
10320469 - 财政年份:2021
- 资助金额:
$ 40.25万 - 项目类别:
Retooling innate immunity: An investigation of TLR-mediated glial priming across lifespan
重组先天免疫:跨生命周期 TLR 介导的神经胶质启动的研究
- 批准号:
10154172 - 财政年份:2021
- 资助金额:
$ 40.25万 - 项目类别:
Linking an activity-dependent BMP pathway to synapse structure and function
将活动依赖性 BMP 通路与突触结构和功能联系起来
- 批准号:
10606602 - 财政年份:2016
- 资助金额:
$ 40.25万 - 项目类别:
Linking an activity-dependent BMP pathway to synapse structure and function
将活动依赖性 BMP 通路与突触结构和功能联系起来
- 批准号:
9078715 - 财政年份:2016
- 资助金额:
$ 40.25万 - 项目类别:
Linking an activity-dependent BMP pathway to synapse structure and function
将活动依赖性 BMP 通路与突触结构和功能联系起来
- 批准号:
10378093 - 财政年份:2016
- 资助金额:
$ 40.25万 - 项目类别:
Establishing a transcriptional pathway for cell-fate and synaptic plasticity
建立细胞命运和突触可塑性的转录途径
- 批准号:
8815445 - 财政年份:2014
- 资助金额:
$ 40.25万 - 项目类别:
Mechanistic analysis of activity-dependent BMP/TGF-beta release at a model synaps
模型突触活性依赖性 BMP/TGF-β 释放的机制分析
- 批准号:
8569373 - 财政年份:2013
- 资助金额:
$ 40.25万 - 项目类别:
Mechanistic analysis of activity-dependent BMP/TGF-beta release at a model synaps
模型突触活性依赖性 BMP/TGF-β 释放的机制分析
- 批准号:
8657126 - 财政年份:2013
- 资助金额:
$ 40.25万 - 项目类别:
Linking motorneuron fate and connectivity in Drosophila
连接果蝇运动神经元的命运和连接
- 批准号:
7779973 - 财政年份:2006
- 资助金额:
$ 40.25万 - 项目类别:
Linking motorneuron fate and connectivity in Drosophila
连接果蝇运动神经元的命运和连接
- 批准号:
7869529 - 财政年份:2006
- 资助金额:
$ 40.25万 - 项目类别:
相似海外基金
Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
- 批准号:
23H01982 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
- 批准号:
23KJ0116 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
- 批准号:
10682794 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
- 批准号:
10598276 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233343 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233342 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
- 批准号:
479363 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
- 批准号:
10681989 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
- 批准号:
2237240 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
- 批准号:
2305592 - 财政年份:2023
- 资助金额:
$ 40.25万 - 项目类别:
Continuing Grant














{{item.name}}会员




