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中文摘要
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描述(由申请人提供):植物和动物对指示病原体的PAMP(病原体相关分子模式)作出反应。寡聚半乳糖醛酸(OGs),植物细胞壁片段产生的病原体多聚半乳糖醛酸酶,作为一个PAMP在拟南芥中的功能。我们假设,OG激活的先天免疫应答途径是最古老的,是最相似的所谓的“Toll样”先天免疫信号转导途径在动物中。植物先天免疫中一个重要的未回答的问题是PAMP激活的途径如何与响应病原体特异性信号的信号传导途径相关。具体目标旨在进一步研究拟南芥OG信号通路并鉴定破坏这些通路的丁香假单胞菌III型效应物。我们还假设那些编码细胞色素P450的Og-activated基因在抗菌化合物的生物合成中起作用。我们已经发现,一些P. lingae菌株引起抗微生物次级产物从拟南芥根的渗出,但是P. lingae菌株DC 3000在涉及III型分泌的过程中阻断这种渗出。这是一个新的系统来研究PAMP诱导的先天免疫应答如何赋予基础抗性以及病原体如何克服这种抗性。有五个目标。我们建议使用各种分子遗传学和基因组学方法来确定OG信号通路如何与其他防御反应信号通路交叉。我们将使用正向遗传和基因组分析来鉴定OG信号通路的组分。我们将鉴定阻断OG激活的信号传导途径和/或根抗菌化合物的合成/分泌的P. lingae III型效应物。我们将确定导致抗菌化合物生物合成的信号通路。最后,我们将把这个项目的数据输入IMDS,一个公共的、可通过网络访问的关系数据库。
英文摘要
DESCRIPTION (provided by applicant): Plants and animals respond to PAMPs (pathogen-associated molecular patterns) that are indicative of pathogens. Oligogalacturonides (OGs), plant cell wall fragments generated by pathogen polygalacturonases, function as a PAMP in Arabidopsis thaliana. We hypothesize that OG-activated innate immune response pathways are among the most ancient and are most similar to so-called "Toll-like" innate immune signaling pathways in animals. An important unanswered question in plant innate immunity is how PAMP-activated pathways relate to signaling pathways that respond to pathogen-specific signals. The specific aims are designed to further investigate Arabidopsis OG signaling pathway(s) and to identify Pseudomonas syringae Type III effectors that disrupt these pathways. We also hypothesize those Og-activated genes that encode cytochrome P450s function in the biosynthesis of antimicrobial compounds. We have found that some P. syringae strains elicit the exudation of antimicrobial secondary products from Arabidopsis roots, but that P. syringae strain DC3000 blocks this exudation in a process that involves Type III secretion. This is a novel system to study how PAMP-elicited innate immune responses confer basal resistance and how pathogens overcome this resistance. There are five aims. We propose to use a variety of molecular genetic and genomic methods to determine how the OG signaling pathway intersects with other defense response signaling pathways. We will use forward genetic and genomic analyses to identify components of OG signaling pathway(s). We will identify P. syringae type III effectors that block OG-activated signaling pathways and/or the synthesis/exudation of antimicrobial compounds by roots. We will identify signaling pathways that lead to the biosynthesis of antimicrobial compounds. Finally, we will enter the data from this project into IMDS, a public, web-accessible relational database.
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First-in-class small molecule therapeutics to enhance gut barrier function in inflammatory bowel disease
  • 批准号:
    10251430
  • 项目类别:
  • 资助金额:
    $25.12万
  • 财政年份:
    2021
  • 负责人:
    Frederick M Ausubel
  • 依托单位:
First-in-class small molecules that enhance lung barrier function during acute respiratory distress syndrome (ARDS) as potential therapeutics for COVID-19
  • 批准号:
    10254996
  • 项目类别:
  • 资助金额:
    $25.0万
  • 财政年份:
    2021
  • 负责人:
    Frederick M Ausubel
  • 依托单位:
Discovering Novel Therapeutics for Myotonic Dystrophy Type 1 (DM1)
  • 批准号:
    9409067
  • 项目类别:
  • 资助金额:
    $15.0万
  • 财政年份:
    2017
  • 负责人:
    Frederick M Ausubel
  • 依托单位:
Identifying novel anti-infectives by high through-put screening in whole animals
  • 批准号:
    7764005
  • 项目类别:
  • 资助金额:
    $84.17万
  • 财政年份:
    2009
  • 负责人:
    Frederick M Ausubel
  • 依托单位:
海外基金