Core B: Analytics for Mucolytics Core

摘要 呼吸道衬里的粘液层是人体抵御吸入的第一道防线 病原体和空气颗粒物。适当地捕获颗粒物和清除肺部是 因此对维持肺功能至关重要。粘液溶解物质分析核心的目标是使用 生化和生物物理研究人员的实验专长，以开发生物标记物的影响 疾病和治疗干预。这些生物标志物将来自多学科的、基础的 该项目的四个项目收集的肺粘液样本的科学表征。这个 分析粘液核心的动机植根于本tPPG的目标，可以概括为 1)阐明黏液阻塞性呼吸道疾病的生物学基础；2)研究黏液阻塞性呼吸道疾病的聚合物， 这些疾病潜在病理的物理基础，以及3)测试粘液溶解和水化的效果 治疗。核心将进一步受到这样的假设的支配，即粘膜阻塞性疾病，如 囊性纤维化和哮喘导致血管内皮细胞生化成分的病理改变 呼吸道粘液，导致粘液层高度浓缩。呼吸道粘液增厚导致 改变生物物理性质，阻碍粘液纤毛清除，最终导致肺功能下降 功能。这种tPPG的治疗目标是开发临床治疗方法，使病理性粘液恢复到 使其处于适当的生化和生物物理状态，从而恢复其正常生理功能。 粘液溶解分析核心将吸收不同团队的研究人员在 马西科·隆研究所开发和实施了新颖的、最先进的实验能力 用于粘液的生化和生物物理性质的表征。核心派，穆罕默德·凯西默博士 是世界公认的粘蛋白生物化学以及如何改变粘液的生化组成的领先者 与肺功能的变化有关。Ehre博士和Livraghi-Butrico博士在 粘蛋白和粘液的生化成像技术，并将这些测量与肺 在动物模型系统和人体受试者中的作用。希尔博士和巴顿博士是生物物理学方面的专家 粘液核心分析公司将分析的广泛粘液样本类型的特征 组成这个TPPG的不同项目。希尔博士和巴顿博士是粘液生物物理学方面的领导者 属性发生生理变化。在一起，这个多元化、多学科的团队带来了一个独特、无与伦比的 核心将用来开发肺生理生物标记物的一套技能。此外，经过验证的赛道 核心研究人员与临床医生协同工作的记录将确保 核心将紧紧地专注于开发生物标记物，这些生物标记物是对生理学的最佳描述 对疾病的影响和评估治疗化合物恢复正常肺功能的疗效。

Abstract The mucus layer lining the respiratory tract acts as the body's first line of defense against inhaled pathogens and airborne particulate matter. Proper trapping of particulates and clearance from the lung is therefore critical to maintaining pulmonary function. The goal of the Analytics for Mucolytics Core is to use the biochemical and biophysical experimental expertise of its investigators to develop biomarkers of the effect of disease and therapeutic interventions. These biomarkers will be derived from a multidisciplinary, basic scientific characterization of pulmonary mucus samples collected by the four Projects of this tPPG. The motivation for the Analytics for Mucolytics Core is rooted in the goals of this tPPG and can be summarize as such: 1) elucidate the biological basis of muco-obstructive airway diseases, 2) investigate the polymeric, physical basis of the underlying pathology of these diseases, and 3) test the efficacy of mucolytic and hydration therapies. The core will be further governed by the hypothesis that muco-obstructive diseases such as cystic fibrosis and asthma cause pathological alterations to the biochemical composition of respiratory mucus, resulting in a hyper-concentrated mucus layer. The thickening of airway mucus leads to altered biophysical properties that impede mucociliary clearance and ultimately cause a decline in lung function. The therapeutic goal of this tPPG is to develop clinical treatments that restore pathological mucus to its proper biochemical and biophysical state, and thereby restore its normal physiological function. The Analytics for Mucolytics Core will draw on the talents of a diverse team of researchers within the Marsico Lung Institute who have developed and implemented novel, state-of-the-art experimental capabilities for the characterization of the biochemical and biophysical properties of mucus. Core PI, Dr. Mehmet Kesimer, is a world-recognized leader of mucin biochemistry and how changes to the biochemical composition of mucus correlate to changes in pulmonary function. Dr. Ehre and Dr. Livraghi-Butrico add a wealth of experience in biochemical imaging techniques of mucins and mucus, and relating these measurements to pulmonary function in animal model systems and human subjects. Dr. Hill and Dr. Button are experts in the biophysical characterization of the wide range of mucus sample types the Analytics for Mucolytics Core will analyze from the diverse projects that make up this tPPG. Dr. Hill and Dr. Button are leaders in relating mucus biophysical properties to physiological changes. Together, this diverse, multidisciplinary team brings a unique, unrivaled set of skills that the core will employ to develop biomarkers of pulmonary physiology. Further, the proven track record of the core investigators working in concert with clinicians will insure that the basic science approach of the core will be tightly focused on developing biomarkers that are the best descriptors of the physiological effect of disease and assess efficacy of therapeutic compounds to restore normal lung function.