Core B: Assay & Cell Models Core

核心 B：检测

基本信息

批准号：
10482425
负责人：
Peter Michael Haggie
金额：
$ 12.82万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10482425
关键词：
Animal Model Basic Science Bicarbonates Biological Assay Cell Culture Techniques Cell Line Cell model Cell physiology Cells Cellular Assay Chemistry Chloride Channels Clone Cells Cystic Fibrosis Transmembrane Conductance Regulator Data Disease Electrophysiology (science)Epithelial Cells Family member Functional disorder Gene Family Gold Homeostasis Human Inbred F344 Rats Ion Channel Lentivirus Libraries Lung Measurement Measures Microscopy Modeling Molecular Biology Mutation Nasal Epithelium Nose Optics Pathogenesis Pharmacology Study Property Research Research Project Grants Resources Rodent Model SLC26A3 gene Signal Transduction Source Structure-Activity Relationship Testing Therapeutic Thyroid Gland Tissue Model Tissues Translational Research Validation Viscosity Workload airway epithelium airway surface liquid analog base bronchial epithelium cell immortalization drug candidate drug development high throughput screening in vitro testing lead candidate lead optimization mutant novel screening small molecule

项目摘要

ABSTRACT The Assays & Cell Models Core (Core B) provides resources for in vitro testing of CF drug candidates identified by high-throughput screening (Core A). Core B performs electrophysiological and optical assays of ion channel and transporter activity, and epithelial cell function, in CF-relevant cell models. The assays use immortalized cell models and primary airway cell cultures from human sources that are generated and provided by the Core. In addition, Core B generates new cell lines to enable screening assays. The assays supported by Core B are critical to the advancement of projects on both pulmonary and non-pulmonary CF diseases manifestations. Core B interfaces directly with all other Cores in the Center, for instance by testing focused analog libraries generated by the Chemistry Core (Core C) in order to prioritize compounds for testing in rodent models (Core D). The most heavily used assay in Core B is measurement of short-circuit current. Other major Core B assays include optical measurements of CF-relevant airway properties, including airway surface liquid (ASL) volume and ionic content (pH, [Cl-], [Na+]). The resources supported by Core B are also available to advance basic and translational research projects on CF pathophysiology at UCSF. Of the 23 projects in the research base, it is anticipated that at least 15 will use Core B resources. The reimagined Assays & Cell Models Core will continue to meet ongoing workloads and adapt to requirements of new projects and research directions.

抽象的测定和细胞模型核心（核心B）为CF候选药物的体外测试提供了资源通过高通量筛选（核心A）确定。核心B执行电生理和光学测定与CF相关的细胞模型中的离子通道和转运蛋白活性以及上皮细胞功能。测定法永生的细胞模型和来自人类来源的原发性气道细胞培养物，并产生由核心提供。此外，Core B会生成新的细胞系以实现筛选测定。测定法由核心B支持对于肺和非肺CF项目的进步至关重要疾病表现。例如，通过测试直接与中心的所有其他内核接口化学核心（Core C）产生的聚焦模拟库，以便优先考虑测试的化合物在啮齿动物模型中（核心D）。核心B中最常用的测定法是对短路电流的测量。其他主要的核心B分析包括对CF相关气道特性的光学测量，包括气道表面液体（ASL）体积和离子含量（pH，[Cl-]，[Na+]）。核心B支持的资源也是可以在UCSF推进有关CF病理生理学的基本和翻译研究项目。 23 研究基础的项目预计至少有15个将使用核心B资源。重新构想测定和细胞模型核心将继续满足正在进行的工作量并适应新项目的要求和研究方向。