In vivo and in silico study of altered airway smooth muscle and extracellular matrix structure and function in the remodelled asthmatic airway

重塑哮喘气道中气道平滑肌和细胞外基质结构和功能改变的体内和计算机研究

• 批准号: 1884572
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1884572
• 关键词: vivo; silico; study; altered; airway

Asthma is a lung disease characterised by inflammation, airway hyper-responsiveness (increased propensity to constrict when stimulated) and airway remodelling (structural changes within the airway wall). In asthma, recurrent inflammation and bronchoconstriction lead to increases in airway smooth muscle mass, altered extra-cellular matrix structure and worsening symptoms. Although remodelling is associated with poor outcomes and asthma deaths it is unclear how the processes relate to whole airway structure and function. This project aims to uncover key mechanisms underlying remodelling and hyper-responsiveness in asthma and thereby identify potential new therapeutic targets. This will be achieved by developing multiscale mathematical models of airway function and remodelling. Models will be based upon detailed anatomical and functional data, including changes in airway microstructure (assessed using novel imaging technologies at the Harwell Research Complex) and consequent function of the airway constituents using state-of-the-art mechanical measurements of the intact airway. This studentship will provide an excellent opportunity to work in an established group at the interface of mathematics, biology and medicine supported by a current MRC-funded project. Training in mathematical/computational modelling, advanced in-vivo skills and imaging will be provided.

哮喘是一种肺部疾病，其特征是炎症、气道高反应性（受到刺激时收缩倾向增加）和气道重塑（气道壁内结构改变）。在哮喘中，反复发作的炎症和支气管收缩导致气道平滑肌质量增加，细胞外基质结构改变和症状恶化。尽管重塑与不良预后和哮喘死亡相关，但尚不清楚该过程与整个气道结构和功能的关系。该项目旨在揭示哮喘重塑和高反应性的关键机制，从而确定潜在的新治疗靶点。这将通过发展气道功能和重塑的多尺度数学模型来实现。模型将基于详细的解剖和功能数据，包括气道微观结构的变化（使用Harwell研究中心的新型成像技术进行评估）以及使用最先进的完整气道机械测量的气道成分的后续功能。该奖学金将提供一个极好的机会，在现有mrc资助的项目支持下，在数学，生物学和医学的界面上建立一个小组。将提供数学/计算建模、高级体内技能和成像方面的培训。