权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Core D: Mucus Biochemistry/Biophysics Core

核心 D：粘液生物化学/生物物理学核心

基本信息

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
项目类别：
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

项目摘要

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、胃肠系统和生殖系统的粘膜表面