Response to Immune Associated Stress

对免疫相关应激的反应

基本信息

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)
专利数量(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:
Response To Immune Associated Stress
对免疫相关应激的反应
  • 批准号:
    10709154
  • 财政年份:
    2020
  • 资助金额:
    $ 47.89万
  • 项目类别:
Response to Immune Associated Stress
对免疫相关应激的反应
  • 批准号:
    10574586
  • 财政年份:
    2020
  • 资助金额:
    $ 47.89万
  • 项目类别:
Response to Immune Associated Stress
对免疫相关应激的反应
  • 批准号:
    9911856
  • 财政年份:
    2020
  • 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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