Basement membrane repair dynamics in the Drosophila midgut

果蝇中肠的基底膜修复动力学

基本信息

  • 批准号:
    10689058
  • 负责人:
  • 金额:
    $ 3.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Basement membranes are the oldest, most conserved forms of extracellular matrix and serve to separate tissue layers, direct signals to neighboring cells, insulate tissues from signals, and provide mechanical support. Further, basement membranes are subject to mechanical damage and require repair. Faulty basement membrane repair can aid in the progression of diseases such as asthma and diabetes, and diseases of the basement membrane itself, including Alport syndrome and Goodpasture syndrome. Therefore, understanding how basement membranes repair will be vital to treating these conditions. My work utilizes the Drosophila midgut basement membrane to probe repair dynamics. In Drosophila, all major basement membrane components have been conserved but with less redundancy than mammals. Our lab has developed an assay to reproducibly damage the basement membrane and study the repair process. Following damage, the basement membrane becomes less stiff and less dense, indicated by a mechanical stress/strain assay and electron microscopy, respectively. Previously it was reported that processes required for basement membrane repair are also required to maintain basement membranes that have not been damaged; these processes include continuous matrix synthesis and regulation of enzymes (matrix metalloproteinases and peroxidasin). Thus, it is unclear whether basement membrane damage is actively detected, or instead, passively repaired by homeostatic mechanisms. My preliminary data suggest basement membrane damage is actively detected. Following damage, the synthesis of matrix components is upregulated in a specific subset of gut epithelial cells we call matrix-makers, and these may be the same cells that express a mechanosensory stretch-activated ion channel, Piezo. This raises the possibility that a change in stiffness of damaged basement membranes signals the initiation of repair. Piezo knockout flies are able to assemble and maintain basement membranes in the adult fly, but, excitingly, Piezo knockouts cannot repair basement membranes after damage. This is evidence of a unique mechanism that detects basement membrane damage and initiates repair. I hypothesize that a loss in matrix stiffness triggers basement membrane repair mechanisms. In Aim 1, I propose to characterize a transient cell population responsible for synthesizing new matrix components following basement membrane damage. In Aim 2, I propose to identify the role of Piezo and its response following basement membrane damage. I expect to identify the first mechanism for detecting and repairing basement membranes. Understanding this mechanism will provide fundamental insights into epithelial biology and will be critical to treating and understanding diseases of the basement membrane.
基底膜是最古老、最保守的细胞外基质形式,用于分离组织

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 }}

AUBRIE STRICKER其他文献

AUBRIE STRICKER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('AUBRIE STRICKER', 18)}}的其他基金

Basement membrane repair dynamics in the Drosophila midgut
果蝇中肠的基底膜修复动力学
  • 批准号:
    10537188
  • 财政年份:
    2022
  • 资助金额:
    $ 3.29万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 3.29万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了