Core B: Analytics for Mucolytics Core

核心 B：粘液溶解核心分析

基本信息

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
项目类别：
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

项目摘要

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.

抽象的呼吸道内壁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。适当捕获颗粒物并从肺部清除是因此对于维持肺功能至关重要。 Analytics for Mucolytics Core 的目标是使用其研究人员的生物化学和生物物理实验专业知识开发了影响的生物标志物疾病和治疗干预。这些生物标志物将源自多学科的基础研究该 tPPG 的四个项目收集的肺粘液样本的科学表征。这粘液溶解核心分析的动机植根于该 tPPG 的目标，可以总结为例如：1）阐明粘液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）测试粘液溶解和水合作用的功效疗法。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生化成分的病理改变呼吸道粘液，导致粘液层高度浓缩。气道粘液增稠导致改变生物物理特性，阻碍粘液纤毛清除并最终导致肺功能下降功能。该 tPPG 的治疗目标是开发将病理性粘液恢复到正常状态的临床治疗方法。使其处于适当的生化和生物物理状态，从而恢复其正常的生理功能。粘液溶解核心分析将利用该领域内多元化研究人员团队的才能 Marsico 肺脏研究所开发并实施了新颖、最先进的实验能力用于表征粘液的生化和生物物理特性。核心 PI，Mehmet Kesimer 博士，是世界公认的粘蛋白生物化学领域的领导者，以及粘液的生化成分如何变化与肺功能的变化相关。 Ehre 博士和 Livraghi-Butrico 博士在以下领域积累了丰富的经验：粘蛋白和粘液的生化成像技术，并将这些测量结果与肺部相关联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领域的专家 Analytics for Mucolytics Core 将分析各种粘液样本类型的特征构成此 tPPG 的各种项目。希尔博士和巴顿博士是粘液生物物理学领域的领导者生理变化的特性。这个多元化、多学科的团队共同带来了独特的、无与伦比的核心将用来开发肺生理学生物标志物的一套技能。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集中于开发生物标志物，这些生物标志物是生理学的最佳描述疾病的影响并评估治疗化合物恢复正常肺功能的功效。