Response to Immune Associated Stress
对免疫相关应激的反应
基本信息
- 批准号:10348727
- 负责人:
- 金额:$ 47.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-13 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:ATP phosphohydrolaseAddressAffectAnimalsAnti-Inflammatory AgentsAutoimmune DiseasesBacterial InfectionsCaenorhabditis elegansCenters for Disease Control and Prevention (U.S.)ChemicalsCommunicable DiseasesComplexDataEndoplasmic Reticulum Degradation PathwayEnsureExposure toFamilyGenesGenetic TranscriptionGoalsHumanImmuneImmune responseInfectionIntestinesInvestigationKnowledgeLaboratoriesLobular NeoplasiaMammalsMembraneModelingNADPH OxidaseOrthologous GeneOxidative StressPathogenicityPathologyPathway interactionsPatientsPharmacologyProcessProductionProtein FamilyPublic HealthPublishingRNA InterferenceReactive Oxygen SpeciesRegulationResearchResistanceRoleSideStressTherapeuticbasebiological adaptation to stressinnovationinsightinterestmembernovelnuclear factor-erythroid 2pathogenpathogen exposurepreventprogramsprotective effectresponsetraffickingtranscription factor
项目摘要
PROJECT SUMMARY/ABSTRACT
Nrf1/2 (human) and SKN-1 (Caenorhabditis elegans ortholog) are key infection-related transcription factors
whose regulation is incompletely understood, representing a critical gap in knowledge. The long-term goal of this
research is to understand how the host alleviates stress during exposure to pathogens. The objective of this
application is to elucidate new mechanisms of SKN-1 regulation that contribute to its protective effects. The
central hypothesis is that NIPI-3 and CDC-48.1/2 are amongst previously unknown factors that positively regulate
SKN-1 to protect against immune associated stress. The rationale for this investigation is that the identification
of new regulators which control a conserved stress response under pathogenic conditions may allow for their
therapeutic modulation to alleviate infection induced pathology. The central hypothesis will be addressed by the
following aims. Specific Aim #1 will identify how NIPI-3 regulates SKN-1 activity. The working hypothesis,
based on preliminary and published data, is that NIPI-3 regulates SKN-1 activity in the intestine via CEBP-1.
Specifically, NIPI-3 is proposed to negatively regulate CEBP-1, to directly influence the amount and/or activity of
SKN-1 available to carry out its protective transcriptional response. Specific Aim #2 will elucidate the role of
CDC-48.1/2 in influencing SKN-1 activity. CDC-48.1/2 is hypothesized to elicit its effects on SKN-1 by its role
in the ER-associated degradation (ERAD) pathway. Specifically, it is proposed that CDC-48.1/2 shuttles SKN-
1A, the ER-tethered form of SKN-1, to the cytosolic side of the ER membrane, a process necessary for its
activation. However, CDC-48.1/2 is additionally predicted to ensure the proper trafficking of BLI-3, a NADPH
oxidase necessary for activating cytoplasmic SKN-1. Specific Aim #3 will identify additional factors that
regulate SKN-1 activity and pathogen resistance. In addition to CDC-48.1/2 and NIPI-3, other factors of in-
terest were found, including two that only affect SKN-1 activity on pathogen. In this aim, the screen will be com-
pleted and additional factors will be characterized. The approach is postulated to reveal further insights into the
mechanisms of SKN-1 regulation. Because SKN-1 and human Nrf orthologs protect against infection-related
stress, the research will have a significant impact on the understanding of the cytoprotective responses that
occur during the immune response. Knowledge of the targets and mechanisms that drive anti-inflammatory re-
sponses may allow for their eventual pharmacological targeting for the benefit of those suffering from damaging
immune responses. The proposed research is innovative because it identifies SKN-1 regulators under infectious
conditions, representing a substantive departure from previous studies.
项目总结/文摘
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)
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Danielle A Garsin其他文献
Vertebrate and invertebrate animal infection models of emCandida auris/em pathogenicity
Candida auris(耳念珠菌)致病性的脊椎动物和无脊椎动物感染模型
- DOI:
10.1016/j.mib.2024.102506 - 发表时间:
2024-08-01 - 期刊:
- 影响因子:7.500
- 作者:
Melissa Martinez;Danielle A Garsin;Michael C Lorenz - 通讯作者:
Michael C Lorenz
Danielle A Garsin的其他文献
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{{ truncateString('Danielle A Garsin', 18)}}的其他基金
Inhibition of Candida Virulence and Biofilm Formation by a Bacterial Peptide
细菌肽抑制念珠菌毒力和生物膜形成
- 批准号:
10302700 - 财政年份:2021
- 资助金额:
$ 47.89万 - 项目类别:
Ethanolamine utilizing bacterial microcompartments in host cells
乙醇胺利用宿主细胞中的细菌微区室
- 批准号:
10495242 - 财政年份:2021
- 资助金额:
$ 47.89万 - 项目类别:
Ethanolamine utilizing bacterial microcompartments in host cells
乙醇胺利用宿主细胞中的细菌微区室
- 批准号:
10385013 - 财政年份:2021
- 资助金额:
$ 47.89万 - 项目类别:
Inhibition of Candida virulence and biofilm formation by a bacterial peptide
细菌肽抑制念珠菌毒力和生物膜形成
- 批准号:
10407531 - 财政年份:2018
- 资助金额:
$ 47.89万 - 项目类别:
Inhibition of Candida virulence and biofilm formation by a bacterial peptide
细菌肽抑制念珠菌毒力和生物膜形成
- 批准号:
10621569 - 财政年份:2018
- 资助金额:
$ 47.89万 - 项目类别:
Post-initiation regulatory mechanisms controlling ethanolamine utilization
控制乙醇胺利用的引发后调节机制
- 批准号:
9193056 - 财政年份:2015
- 资助金额:
$ 47.89万 - 项目类别:
Mechanism of Gene Regulation by RNA-Binding ANTAR Proteins
RNA结合ANTAR蛋白的基因调控机制
- 批准号:
8325259 - 财政年份:2011
- 资助金额:
$ 47.89万 - 项目类别:
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