Core D: Mucus Biochemistry/Biophysics Core

核心 D：粘液生物化学/生物物理学核心

• 批准号: 10227488
• 负责人: BRIAN M BUTTON
• 金额: $ 17.93万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10227488
• 关键词: Adhesions; Affect; Animals; Antibodies; Area; Atomic Force Microscopy; Bacteria; Basic Science; Bicarbonates; Biochemical; Biochemistry; Biological Assay; Biophysics; Biopsy; Cell model; Cell surface; Cells; Characteristics; Chlorides; Cilia; Collaborations; Complex Mixtures; Coupled; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA; Data; Dehydration; Disease; Doctor of Philosophy; Environment; Epithelial; Epithelial Cells; Event; Exhibits; Exposure to; Fluorescent in Situ Hybridization; Friction; Functional disorder; Gastrointestinal tract structure; Gel; Glycoproteins; Goals; Health; Human; Image; In Vitro; Individual; Inflammatory Response; Intestines; Ion Transport; Irrigation; Laboratories; Lung; MUC5AC gene; MUC5B gene; Measurement; Measures; Mediating; Molecular Weight; Mucin 1 protein; Mucin-2 Staining Method; Mucins; Mucous Membrane; Mucous body substance; Normal Range; Organ; Osmotic Pressure; Pathogenesis; Patients; Persons; Pharmacology; Play; Positioning Attribute; Property; Proteins; Reagent; Reproductive system; Research; Research Personnel; Respiratory System; Role; Salts; Sampling; Scanning Electron Microscopy; Scientist; Series; Services; Small Intestines; Solid; Surface; System; Techniques; Technology; Therapeutic; Therapeutic Agents; Therapeutic Effect; Toxin; Translations; Water; airway epithelium; antimicrobial peptide; biophysical properties; body system; cystic fibrosis mucus; design; drug development; extracellular; gastrointestinal; gastrointestinal system; histological image; in vitro Assay; molecular size; mucus clearance; new technology; novel; pathogen; persistent bacterial infection; reproductive tract; tissue/cell culture; tool; viscoelasticity; zeta potential

The mucosal surfaces of the respiratory, gastrointestinal, and reproductive systems are continually exposed to the exterior environment. In health, the continual clearance of a luminal mucus layer in these organ systems represents a key component of innate defense against disease. However, in people with cystic fibrosis (pwCF), abnormal mucus clearance represents a key contributor to disease pathogenesis. Over the last decade, our studies have revealed that CFTR dysfunction in pwCF leads to epithelial surface layer volume depletion and, thus, “dehydration” of the overlying mucus layer. This increased mucus concentration, coupled with disease-related mucin overproduction, results in mucus adhesion to epithelial surfaces and mucostasis. It is likely that adhesion of the mucus to the epithelial surface represents an initiating event in the pathogenesis of the CF in both the lung and gut. Static mucus constitutes the nidus for the persistent bacterial infection that provokes an ineffective inflammatory response in the airways and likely small intestine (i.e., small bowel overgrowth). Given the importance of understanding the role that mucus and mucins play in CF pathogenesis in both the GI system and lungs, the goal of the Mucus Biochemical and Biophysical Core (Core D) is to provide both internal and external researchers access to a unique spectrum of tools and reagents necessary for understanding the biochemical and biophysical properties of mucus/mucins in health and pwCF. To this end, Core D laboratories offer a series of novel techniques developed to directly measure key mucus biochemical and biophysical properties, including mucin concentration, osmotic pressure, adhesion strength, cell surface frictional interactions, and viscous and elastic moduli. Collectively, these measurements will facilitate an understanding of how abnormal mucus in CF produces adherent, static, mucus and to identify optimal combinations of pharmacological agent(s) to restore/accelerate the rate of mucus transport in people with CF. The main goal of the UNC Mucus Biochemistry and Biophysics Core is to provide investigators data from these specialized mucus/mucin assays that are either not possible or feasible in their labs. Core D is uniquely positioned to: 1) investigate the properties of user supplied mucus samples; and 2) assess the impact of therapeutic agents, supplied by investigators, to reduce mucus accumulation and accelerate mucus clearance. A strength of this Core is the collaboration of a group of scientists who are experts in the field of mucus/mucin analysis. The benefit to potential Core users is the ability to generate data utilizing our novel techniques, freeing individual investigators to focus on basic science, and drug development.

呼吸系统、胃肠道和生殖系统的粘膜表面是 持续暴露于外部环境在健康中，管腔的持续间隙。 这些器官系统中的粘液层代表了先天防御的关键组成部分 然而，对于患有囊性纤维化（pwCF）的人来说，粘液清除异常代表着一种疾病。 在过去的十年中，我们的研究表明，疾病发病机制的关键因素。 pwCF 中的 CFTR 功能障碍导致上皮表面层体积减少，因此， 上面的粘液层“脱水”，再加上粘液浓度增加。 与疾病相关的粘蛋白过量产生，导致粘液粘附到上皮表面， 粘液对上皮表面的粘附可能是一种起始因素。 肺部和肠道中的 CF 发病机制中的事件构成了病灶。 对于持续的细菌感染会引起无效的炎症反应 气道和可能的小肠（即小肠过度生长）。 了解粘液和粘蛋白在胃肠道系统和 CF 发病机制中的作用 对于肺部，粘液生化和生物物理核心（核心 D）的目标是提供内部 和外部研究人员可以获得所需的一系列独特的工具和试剂 了解健康和 pwCF 中粘液/粘蛋白的生化和生物物理特性。 为此，Core D 实验室提供了一系列新技术来直接测量 关键粘液生化和生物物理特性，包括粘蛋白浓度、渗透压 压力、粘附强度、细胞表面摩擦相互作用以及粘性和弹性模量。 总的来说，这些测量将有助于了解 CF 中的异常粘液如何 产生粘附的、静态的、粘液并确定药理学的最佳组合 恢复/加速 CF 患者粘液运输速率的药物 该项目的主要目标。 北卡罗来纳大学粘液生物化学和生物物理学核心将为研究人员提供这些数据 Core D 是不可能或不可行的专门粘液/粘蛋白测定。 具有独特的优势：1) 研究用户提供的粘液样本的特性；2) 评估研究人员提供的治疗剂对减少粘液积聚的影响 并加速粘液清除 该核心的优势在于一群人的协作。 粘液/粘蛋白分析领域的专家科学家对潜在核心用户的好处。 是利用我们的新技术生成数据的能力，使个人调查人员能够 专注于基础科学和药物开发。