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 持续暴露在外部环境中。在健康的情况下，持续清除管腔 这些器官系统中的粘液层是先天防御的关键组成部分 疾病然而，在患有囊性纤维化（CSFCF）的人中，异常的粘液清除代表了一种疾病。 疾病发病机制的关键贡献者。在过去的十年里，我们的研究表明， CFTR功能障碍导致上皮细胞表面层体积减少，因此， 上覆粘液层的“脱水”。这增加了粘液浓度，加上 疾病相关的粘蛋白过度产生，导致粘液粘附到上皮表面， 粘液淤滞。很可能是粘液粘附到上皮表面代表了一种启动 在肺和肠中的CF发病机制中的事件。静止的粘液构成病灶 对于持续性细菌感染，引起无效的炎症反应， 气道和可能的小肠（即，小肠过度生长）。鉴于必须 了解粘液和粘蛋白在胃肠道系统和 肺，粘液生化和生物物理核心（核心D）的目标是提供两个内部 和外部研究人员获得所需的独特的工具和试剂谱， 了解粘液/粘蛋白在健康和慢性前列腺炎中的生物化学和生物物理特性。 为此，核心D实验室提供了一系列新的技术开发，以直接测量 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 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患者粘液转运速率的药物。的主要目标 Mucus Biochemistry and Biophysics Core是为研究者提供来自这些领域的数据， 在他们的实验室中不可能或不可行的专门的粘液/粘蛋白测定。核心D是 独特定位以：1）研究用户提供的粘液样品的性质;以及2） 评估研究者提供的治疗药物对减少粘液积聚的影响 加速粘液清除这个核心的一个优势是一群 粘液/粘蛋白分析领域的专家。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， 专注于基础科学和药物开发。