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.

呼吸道，胃肠道和生殖系统的粘膜表面是 继续暴露于外部环境。在健康方面，腔的连续清除 这些器官系统中的粘液层代表了天生防御的关键组成部分 疾病。但是，在囊性纤维化（PWCF）的人中，异常粘液清除率代表 疾病发病机理的关键因素。在过去的十年中，我们的研究表明 PWCF中的CFTR功能障碍会导致上皮表面层体积部署，因此 上覆粘液层的“脱水”。这增加了粘液浓度，并与 与疾病相关的粘蛋白过量产生，导致粘液粘合到上皮表面和 粘液症。粘液对上皮表面的粘附可能代表 在肺和肠道中CF发病机理中的事件。静态粘液构成Nidus 对于持续的细菌感染引起了无效的炎症反应 气道和可能的小肠（即小肠过度生长）。考虑到重要性 了解粘液和粘蛋白在GI系统和GI系统中的CF发病机理中的作用 肺，粘液生化和生物物理核心（核心D）的目标是提供内部 外部研究人员可以访问必要的独特工具和试剂范围 了解粘液/粘蛋白在健康和pwcf中的生化和生物物理特性。 为此，核心D实验室提供了一系列用于直接测量的新技术 关键的粘液生化和生物物理特性，包括粘蛋白浓度，渗透 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中异常粘液 产生粘附，静态，粘液并识别药物的最佳组合 CF患者中恢复/加速粘液运输速率的代理。主要目标 UNC粘液生物化学和生物物理学核心是提供研究人员的数据 在其实验室中不可能或可行的专门粘液/粘蛋白测定。核心是 独特地定位于：1）研究用户提供的粘液样品的特性；和2） 评估研究人员提供的治疗剂的影响，以减少粘液积累 并加速粘液清除。这个核心的优势是一群合作 是粘液/粘蛋白分析领域专家的科学家。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，使个人研究人员释放 专注于基础科学和药物开发。