Diversity Supplement: Understanding mucus composition and function in asthma

多样性补充:了解哮喘中的粘液成分和功能

基本信息

  • 批准号:
    10834550
  • 负责人:
  • 金额:
    $ 6万
  • 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:
    2022-07-01 至 2027-04-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY As asthma worsens, occlusion of airways with mucus significantly contributes to airflow obstruction. Recent evidence has suggested mucus obtained from individuals with severe asthma possesses altered mucin composition. However, how these changes alter the functional properties of the mucus gel is not yet fully understood. The overall objectives in this application are to (i) establish new models where mucus composition can be precisely controlled for mechanistic assessment of its function and (ii) understand the role of mucus composition in viral infection-induced exacerbation of disease. The central hypothesis is airway mucus with an imbalanced concentration of the 2 primary gel-forming airway mucins, MUC5B and MUC5AC, possesses significantly altered biophysical properties that leads to impaired function in asthma. The central hypothesis will be tested through development of two new model systems: a bioengineered hydrogel that mimics native mucus and a genetically engineered human lung tissue culture model capable of producing mucus with a composition representative of healthy and asthmatic airways. In comparison to the standard models used, the primary advantage of our model systems is the capability to systematically vary the composition of mucus to capture how these changes might impact its physiological function. Our approach will enable for a mechanistic understanding of conditions under which the mucus gel becomes immobile, thus reduces its ability to be effectively cleared and increases the likelihood for mucus plug formation in the lungs of individuals with asthma. In addition, the impact of composition on the barrier function of mucus towards influenza virus will be examined using these state-of-the art model systems and a transgenic mouse model of severe asthma. The research proposed in this application is innovative as it employs tools from molecular biology, biophysics, and engineering to develop a novel means to control and assess mucus composition by closely mimicking its properties in healthy and asthmatic airways. If successful, the results of this work will be significant as our approach may provide new insights into the biological function of mucus in asthma, also with relevance to other related muco-obstructive lung diseases.
项目摘要 当哮喘发作时,气道被粘液阻塞显著地导致气流阻塞。最近 有证据表明,从严重哮喘患者身上获得的粘液具有改变的粘蛋白 混合物.然而,这些变化如何改变粘液凝胶的功能特性, 明白本申请的总体目标是(i)建立新的模型,其中粘液成分 可以精确地控制其功能的机械评估和(ii)了解粘液的作用 本发明的组合物在病毒感染诱导的疾病恶化中的用途。中心假设是气道粘液, 2种主要的形成凝胶的气道粘蛋白MUC5B和MUC5AC的浓度不平衡, 显著改变的生物物理特性,导致哮喘功能受损。核心假设 将通过开发两种新的模型系统进行测试:一种生物工程水凝胶, 粘液和能够产生粘液的基因工程人肺组织培养模型, 代表健康和哮喘气道的组合物。与使用的标准模型相比, 我们的模型系统的主要优点是能够系统地改变粘液的组成, 捕捉这些变化如何影响其生理功能。我们的方法将使一个机械的 了解粘液凝胶变得不动的条件,从而降低了其被 有效清除,并增加了肺粘液栓形成的可能性, 哮喘此外,组合物对粘液对流感病毒的屏障功能的影响将被进一步研究。 使用这些现有技术的模型系统和严重哮喘的转基因小鼠模型进行检查。的 在这项申请中提出的研究是创新的,因为它采用了分子生物学,生物物理学和 工程开发一种新的手段来控制和评估粘液组成,通过密切模仿其 健康和哮喘气道的特性。如果成功,这项工作的成果将是重要的,因为我们的 这种方法可能为哮喘中粘液的生物学功能提供新的见解,也与其他相关性。 相关的粘膜阻塞性肺病。

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 }}

Gregg Duncan其他文献

Gregg Duncan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('Gregg Duncan', 18)}}的其他基金

Understanding alterations to mucus composition and function in asthma
了解哮喘中粘液成分和功能的改变
  • 批准号:
    10641012
  • 财政年份:
    2022
  • 资助金额:
    $ 6万
  • 项目类别:

相似海外基金

Defining new asthma phenotypes using high-dimensional data
使用高维数据定义新的哮喘表型
  • 批准号:
    2901112
  • 财政年份:
    2024
  • 资助金额:
    $ 6万
  • 项目类别:
    Studentship
Air pollution and Asthma in Canada: Projections of burden and the value of climate adaptation strategies
加拿大的空气污染和哮喘:负担预测和气候适应战略的价值
  • 批准号:
    485322
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
    Operating Grants
Data-driven model links BMIz to gene expression in pediatric asthma
数据驱动模型将 BMIz 与小儿哮喘基因表达联系起来
  • 批准号:
    493135
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
BIOlogic drug safety and effectiveness interNational pharmacoepidemiologIC study in pregnant women with autoimmune disorders and asthma and their children (BIONIC)
患有自身免疫性疾病和哮喘的孕妇及其子女的生物药物安全性和有效性国际药物流行病学研究(BIONIC)
  • 批准号:
    493526
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
    Operating Grants
Engaging Patient and Caregivers in Using Patient-reported Outcomes Measures in Pediatric Clinical Care for Asthma
让患者和护理人员参与儿科哮喘儿科临床护理中患者报告的结果测量
  • 批准号:
    495593
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
Basophilic oncostatin M fuels nociceptor neuron-induced asthma
嗜碱性制瘤素 M 促进伤害感受器神经元诱发哮喘
  • 批准号:
    485504
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
    Salary Programs
Mechanistic Study of Inspiratory Training in Childhood Asthma
儿童哮喘吸气训练机制研究
  • 批准号:
    10637048
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
Early life exposure to metal mixtures: impacts on asthma and lungdevelopment
生命早期接触金属混合物:对哮喘和肺部发育的影响
  • 批准号:
    10678307
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
Lung resident Treg suppression of Th2 resident memory T cells in allergic asthma
过敏性哮喘中肺常驻 Treg 对 Th2 常驻记忆 T 细胞的抑制
  • 批准号:
    10664599
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
  • 批准号:
    10813753
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了