Core B: Analytics for Mucolytics Core

核心 B：粘液溶解核心分析

• 批准号: 10001595
• 负责人: Mehmet Kesimer
• 金额: $ 32.19万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-07 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001595
• 关键词: Airborne Particulate Matter; Animal Model; Asthma; Basic Science; Biochemical; Biochemistry; Biological; Biological Assay; Biological Markers; Biological Models; Biophysics; Clinical; Clinical Treatment; Communities; Cone; Coughing; Cystic Fibrosis; Descriptor; Development; Diffusion; Disease; Doctor of Philosophy; Epithelial; Epithelium; Functional disorder; Gel; Goals; Hydration status; Imaging Techniques; Impairment; Individual; Inhalation; Institutes; Intervention; Laboratories; Lasers; Lung; Lung diseases; MUC5AC gene; MUC5B gene; Mass Spectrum Analysis; Measurement; Measures; Medicine; Microscopic; Microspheres; Molecular; Molecular Structure; Molecular Weight; Motivation; Mucin-2 Staining Method; Mucins; Mucociliary Clearance; Mucolytics; Mucous body substance; North Carolina; Obstructive Lung Diseases; Osmotic Pressure; Particulate; Pathologic; Pathology; Pediatrics; Physics; Physiological; Physiology; Plant Roots; Polymers; Principal Investigator; Property; Radial; Reducing Agents; Refractometry; Research; Research Personnel; Respiratory System; Respiratory physiology; Rheology; Sampling; Solid; Structure; Sulfhydryl Compounds; Talents; Techniques; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Treatment Efficacy; Universities; Viscosity; Water; Weight; Western Blotting; biophysical properties; clinical efficacy; cohesion; disulfide bond; disulfide bond reduction; efficacy testing; experience; human subject; light scattering; mid-career faculty; monomer; multidisciplinary; novel; pathogen; professor; pulmonary function; respiratory; skills; stable isotope; viscoelasticity

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.

摘要 呼吸道内的粘液层是人体抵御吸入的第一道防线 病原体和空气中的颗粒物。适当捕获微粒并从肺部清除， 因此对维持肺功能至关重要。粘液溶解核心分析的目标是使用 研究人员的生物化学和生物物理实验专业知识，以开发生物标志物的影响， 疾病和治疗干预。这些生物标志物将来自多学科的，基本的 本tPPG的四个项目采集的肺粘液样本的科学表征。的 粘液溶解分析核心的动机植根于本tPPG的目标，可总结为 例如：1）阐明粘膜阻塞性气道疾病的生物学基础，2）研究聚合物， 这些疾病的潜在病理学的物理基础，以及3）测试粘液溶解和水化的功效 治疗核心将进一步受到以下假设的支配：粘液阻塞性疾病，例如 囊性纤维化和哮喘引起的病理改变的生化组成， 呼吸道粘液，导致高度浓缩的粘液层。气道粘液增厚导致 改变的生物物理特性，阻碍粘膜纤毛清除，并最终导致肺功能下降， 功能该tPPG的治疗目标是开发临床治疗， 恢复其正常的生物化学和生物物理状态，从而恢复其正常的生理功能。 Mucolytics核心分析将利用该领域内多元化研究团队的人才， Marsico Lung研究所开发并实施了新颖的，最先进的实验能力 用于表征粘液的生物化学和生物物理性质。核心PI，Mehmet Kesimer博士， 是世界公认的粘蛋白生物化学的领导者， 与肺功能的变化有关。Ehre博士和Livraghi-Butrico博士在以下方面积累了丰富的经验： 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类受试者中发挥作用。希尔博士和巴顿博士是生物物理学方面的专家 粘液溶解分析核心将分析的各种粘液样本类型的表征 组成这个tPPG的各种项目。希尔博士和巴顿博士是将粘液生物物理学 属性到生理变化。这支多元化、多学科的团队共同带来了一个独特的、无与伦比的 核心将采用一套技能来开发肺生理学的生物标志物。此外，经过验证的轨道 核心研究人员与临床医生合作的记录将确保基础科学方法， 核心将紧紧集中在开发生物标志物上，这些生物标志物是生理学的最佳描述符， 并评估治疗性化合物恢复正常肺功能功效。