Innate immune signaling and stress response
Innate immune signaling and stress response
批准号:
9901240
负责人:
Thirumala-Devi Kanneganti
金额:
$53.85万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-03-15 至 2026-02-28
关键词:
AffectAffinity ChromatographyAntiviral AgentsApoptosisAreaBiological ProcessCASP1 geneCell DeathCell SurvivalCellsCellular StressCellular Stress ResponseCommunicable DiseasesCuesCytosolDataGrantHealthHomeostasisHumanImmuneImmune responseImmune signalingImmunityImmunologyInfectionInflammasomeInflammationInflammatoryInflammatory ResponseInfluenza A virusInnate Immune ResponseInterleukin-1 betaInterleukin-18LinkMalignant NeoplasmsMass Spectrum AnalysisMediatingMolecularMusMutationMyeloid CellsNatural ImmunityNatureNeurodegenerative DisordersPathogenicityPathway interactionsPatternPhysiologicalPlayPositioning AttributeProductionProgress ReportsPublicationsPublishingRNARegulationRoleScienceSignal PathwaySignal TransductionStressStructureSyndromeTestingViralVirusVirus DiseasesZ-DNA Binding Proteinbiological adaptation to stresscytokineexperimental studyhelicasehuman diseasein vivoinfluenza infectioninfluenzavirusinnate immune pathwaysinterestmicrobialnew therapeutic targetpathogenpathogenic microbeprotein complexreceptorresponsesensorstress granuletargeted treatment
中文摘要
摘要:
--
无膜隔室在维持人体细胞功能和机体内环境平衡方面发挥着至关重要的作用。
调节细胞存活,调节细胞死亡。应激颗粒、细菌和炎症体诱导的细胞斑点。
无膜隔膜提供了一种截然不同的细胞和命运选择,以确保细胞的生存能力或下垂。
(程序化的细胞死亡)在生理性死亡或病毒诱导的细胞死亡期间发生。
病原体相关基因模式(PAMPs)和危险相关基因模式(DAMPS),
感觉细胞内的扰动发生在胞浆中,从而触发了一个很大的半胱氨酸天冬氨酸酶-1激活的蛋白质的组装过程。
该复合体被称为NLRP3的炎症体。由于NLRP3的存在,Caspase-1的自身蛋白分解和成熟过程。
炎症体激活可导致下垂、促炎性细胞因子和白介素2的成熟障碍--
1β和IL-18.尽管NLRP3没有能力对细胞因子或病毒诱导的应激反应的不同信号做出反应。
控制炎症小体之间的相互作用和压力颗粒之间的相互作用的机制仍然难以捉摸。
Quest希望对这一串音进行研究,我们已经确定DDX3X是一种主要的应激颗粒成分,也是一种上游成分。
监管机构表示,NLRP3的炎症体可能会引发规范的病毒感染,并引发病毒感染。在这次R01的更新中,我们可能会提出进一步识别的建议。
DDX3X介导的NLPR3激活炎症小体的分子调控和细胞调控机制及其机制。
在炎症反应和病毒感染过程中,应激信号的调制。我们理解了人与人之间的相互作用。
细胞免疫应激、分子反应和先天免疫信号传导机制将引领人们寻找新的治疗药物靶点。
炎症性疾病和传染性疾病。
英文摘要
ABSTRACT
Membraneless compartments play a vital role in maintaining cellular and organismal homeostasis by
modulating cell survival and cell death. Stress granules, and inflammasome-induced specks are
membraneless compartments that provide contrasting cell fate choices to the cells – survival or pyroptosis
(programmed cell death) during physiological or virus induced cellular stress. NLRP3, a global sensor of
pathogen–associated molecular patterns (PAMPs) and danger–associated molecular patterns (DAMPs),
senses cellular perturbations in the cytosol to trigger the assembly of a large caspase-1-activating protein
complex termed the NLRP3 inflammasome. Autoproteolytic maturation of caspase-1 due to NLRP3
inflammasome activation leads to pyroptosis, and maturation of pro-inflammatory cytokines interleukin (IL)-
1β and IL-18. Despite the ability of NLRP3 to respond to diverse cues of cellular or virus induced stress,
mechanisms controlling the cross-talk between inflammasomes and stress granules remain elusive. In our
quest to study this cross-talk, we have identified DDX3X, a stress granule component, as an upstream
regulator of NLRP3 inflammasome to canonical and viral triggers. In this R01 renewal, we propose to identify
the molecular and cellular mechanisms of DDX3X-mediated NLPR3 inflammasome activation and its
modulation by stress signals during inflammation and viral infections. Understanding the cross-talk between
cellular stress response molecules and innate immune signaling will lead to novel therapeutic targets for
inflammatory and infectious diseases.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:10631757
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财政年份:2021
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依托单位:
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批准号:10428652
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资助金额:$76.38万
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批准号:10311802
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资助金额:$76.38万
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依托单位:
Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer
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批准号:10633206
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资助金额:$105.55万
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财政年份:2020
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Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer
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批准号:10220912
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资助金额:$107.7万
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财政年份:2020
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate immune sensors, inflammasomes, and inflammasome-mediated processes in cancer
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批准号:10442693
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资助金额:$100.88万
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财政年份:2020
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负责人:Thirumala-Devi Kanneganti
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依托单位:
The Non-Inflammasome NLRs in Immunity and Host defense
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批准号:9243972
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项目类别:
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资助金额:$44.88万
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财政年份:2016
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate immune signaling and stress response
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批准号:10327667
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项目类别:
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资助金额:$53.85万
-
财政年份:2016
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate immune signaling and stress response
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批准号:10574531
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项目类别:
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资助金额:$53.85万
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财政年份:2016
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:9127673
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项目类别:
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资助金额:$44.88万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
NLR signaling in colitis and colorectal tumorigenesis
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批准号:8831610
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项目类别:
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资助金额:$36.31万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:8827667
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项目类别:
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资助金额:$43.75万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:9912091
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项目类别:
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资助金额:$44.88万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:10295212
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项目类别:
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资助金额:$45.5万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate signaling pathways in colitis and colorectal tumorigenesis
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批准号:9120535
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项目类别:
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资助金额:$42.63万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Inflammatory Caspases in Innate Immunity and Inflammation
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批准号:8365332
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项目类别:
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资助金额:$43.75万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
NLR signaling in colitis and colorectal tumorigenesis
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批准号:8373063
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项目类别:
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资助金额:$36.31万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
Innate signaling pathways in colitis and colorectal tumorigenesis
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批准号:9892953
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项目类别:
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资助金额:$42.63万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
NLR signaling in colitis and colorectal tumorigenesis
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批准号:8507633
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项目类别:
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资助金额:$34.13万
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财政年份:2012
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负责人:Thirumala-Devi Kanneganti
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依托单位:
海外基金