Screening Device for Differentiated Primary Cell Models of Airway Epithelia

气道上皮分化原代细胞模型筛选装置

基本信息

  • 批准号:
    8315901
  • 负责人:
  • 金额:
    $ 53.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-04-01 至 2014-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Approaches to drug screening typically involve dramatic compromises in order to achieve high throughput and hold down costs. Examples include the use of immortalized, heterologous cell lines, and genetic engineering to over-express the target protein and/or incorporate a fluorescent surrogate reporter to display the result. At least partly because such systems often produce responses that are not relevant to the actual human disease state, high throughput screening has not historically delivered a strong return on investment. More representative primary cell models are often available for tissues and diseases, but these models are underutilized in screening because of the lack of technological solutions and high costs. For similar reasons, more relevant assay technologies such as endogenous immunocytochemistry and electrophysiology are not commonly employed in HTS. The goal of this project is to bring the gold standard, organotypic cell model for airway epithelia into true high throughput screening, and enable the use of more informative high content assays including endogenous CFTR trafficking and airway surface liquid height. In addition to applications for cystic fibrosis and COPD, the resultant device will also be valuable for skin models and drug transport studies. The device consists of an array of 96 microchambers in standard microplate format. The microchamber design is small enough to be compatible with 384-well plate densities, so 384 microchambers per plate is readily achievable. The plate includes specialized features for compatibility and ease-of-use with standard liquid handling robotics, and high resolution microscopy. Importantly, the device is simple enough to be produced at a cost consistent with the cost constraints of HTS labs, and confers dramatic savings in primary cell and media consumption. The feasibility study on a small-scale device was successfully completed, indicating that the highly miniaturized approach is compatible with organotypic epithelial airway culture at air-liquid interface. Although not an aim of this proposal this device is designed to be integrated into an electrophysiology instrument designed specifically for this culture system. PUBLIC HEALTH RELEVANCE: The project seeks to develop an automatable device that uses the best possible cell models for airways disease, and the best possible tests or assays for the critical functions of human airways. The goal is to help improve the success ratios of bringing a candidate drug to the market for airways diseases like cystic fibrosis and chronic obstructive pulmonary disorder. The device will also be useful for finding drugs for other diseases like skin cancer and certain kidney diseases.
描述(由申请人提供):药物筛选的方法通常涉及戏剧性的妥协,以实现高通量和压低成本。实例包括使用永生化的异源细胞系和基因工程来过表达靶蛋白和/或掺入荧光替代报告物以显示结果。至少部分地因为这样的系统通常产生与实际人类疾病状态不相关的响应,高通量筛选在历史上没有提供强有力的投资回报。对于组织和疾病,通常可以获得更具代表性的原代细胞模型,但由于缺乏技术解决方案和成本高昂,这些模型在筛选中未得到充分利用。出于类似的原因,更相关的检测技术,如内源性免疫细胞化学和电生理学,通常不采用HTS。该项目的目标是将气道上皮细胞的金标准、器官型细胞模型引入真正的高通量筛选,并能够使用更多信息的高含量测定,包括内源性CFTR运输和气道表面液体高度。除了囊性纤维化和COPD的应用外,所得到的设备也将对皮肤模型和药物转运研究有价值。该装置由标准微孔板格式的96个微室阵列组成。微室设计足够小以与384孔板密度兼容,因此每个板384个微室是容易实现的。该板包括与标准液体处理机器人和高分辨率显微镜兼容和易于使用的专门功能。重要的是,该装置足够简单,可以以与HTS实验室的成本限制一致的成本生产,并在原代细胞和培养基消耗方面提供了显着的节省。成功完成了小型装置的可行性研究,表明高度小型化的方法与气液界面的器官型上皮气道培养相容。虽然不是本提案的目的,但该器械设计为集成到专门为此培养系统设计的电生理仪器中。 公共卫生关系:该项目旨在开发一种可自动化的设备,使用最好的气道疾病细胞模型,以及最好的人类气道关键功能测试或分析。其目标是帮助提高将候选药物推向市场的成功率,用于治疗囊性纤维化和慢性阻塞性肺病等气道疾病。该设备还将用于寻找治疗皮肤癌和某些肾脏疾病等其他疾病的药物。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Robert G Lowery其他文献

Robert G Lowery的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Robert G Lowery', 18)}}的其他基金

Targeting a Human Acyltransferase for Broad-Spectrum Antivirals
靶向人类酰基转移酶的广谱抗病毒药物
  • 批准号:
    10223496
  • 财政年份:
    2021
  • 资助金额:
    $ 53.96万
  • 项目类别:
Discovery of cGAS Inhibitors for Interferon-Driven Autoimmune Diseases
发现用于治疗干扰素驱动的自身免疫性疾病的 cGAS 抑制剂
  • 批准号:
    10258171
  • 财政年份:
    2019
  • 资助金额:
    $ 53.96万
  • 项目类别:
Discovery of cGAS Inhibitors for Interferon-Driven Autoimmune Diseases
发现用于治疗干扰素驱动的自身免疫性疾病的 cGAS 抑制剂
  • 批准号:
    10349593
  • 财政年份:
    2019
  • 资助金额:
    $ 53.96万
  • 项目类别:
HTS Assays for Targeting the cGAS-STING Pathway in Autoimmune Diseases and Cancer
针对自身免疫性疾病和癌症中的 cGAS-STING 通路的 HTS 检测
  • 批准号:
    9347049
  • 财政年份:
    2017
  • 资助金额:
    $ 53.96万
  • 项目类别:
Riboswitch Based Methyltransferase HTS Assay for Epigenetic Drug Discovery
基于核糖开关的甲基转移酶 HTS 测定用于表观遗传药物发现
  • 批准号:
    9266793
  • 财政年份:
    2014
  • 资助金额:
    $ 53.96万
  • 项目类别:
Riboswitch Based Methyltransferase HTS Assay for Epigenetic Drug Discovery
基于核糖开关的甲基转移酶 HTS 测定用于表观遗传药物发现
  • 批准号:
    8646158
  • 财政年份:
    2014
  • 资助金额:
    $ 53.96万
  • 项目类别:
Riboswitch Based Methyltransferase HTS Assay for Epigenetic Drug Discovery
基于核糖开关的甲基转移酶 HTS 测定用于表观遗传药物发现
  • 批准号:
    9140743
  • 财政年份:
    2014
  • 资助金额:
    $ 53.96万
  • 项目类别:
High Throughput Assay for Detecting Protein Modifications in Cell Lysates
用于检测细胞裂解物中蛋白质修饰的高通量测定
  • 批准号:
    8124311
  • 财政年份:
    2011
  • 资助金额:
    $ 53.96万
  • 项目类别:
Screening Device for Differentiated Primary Cell Models of Airway Epithelia
气道上皮分化原代细胞模型筛选装置
  • 批准号:
    8515510
  • 财政年份:
    2010
  • 资助金额:
    $ 53.96万
  • 项目类别:
Intramolecular Immunoassay for Probing Paracrine Signaling
用于探测旁分泌信号传导的分子内免疫分析
  • 批准号:
    8001695
  • 财政年份:
    2010
  • 资助金额:
    $ 53.96万
  • 项目类别:

相似国自然基金

湍流和化学交互作用对H2-Air-H2O微混燃烧中NO生成的影响研究
  • 批准号:
    51976048
  • 批准年份:
    2019
  • 资助金额:
    61.0 万元
  • 项目类别:
    面上项目

相似海外基金

COMPAS: co integration of microelectronics and photonics for air and water sensors
COMPAS:微电子学和光子学的共同集成,用于空气和水传感器
  • 批准号:
    10108154
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    EU-Funded
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Standard Grant
SBIR Phase I: High-Efficiency Liquid Desiccant Regenerator for Desiccant Enhanced Evaporative Air Conditioning
SBIR 第一阶段:用于干燥剂增强蒸发空调的高效液体干燥剂再生器
  • 批准号:
    2335500
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Standard Grant
Catalyzing Sustainable Air Travel: Unveiling Consumer Willingness to Pay for Sustainable Aviation Fuel through Information Treatment in Choice Experiment and Cross-Country Analysis
促进可持续航空旅行:通过选择实验和跨国分析中的信息处理揭示消费者支付可持续航空燃油的意愿
  • 批准号:
    24K16365
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Collaborative Research: Phenotypic and lineage diversification after key innovation(s): multiple evolutionary pathways to air-breathing in labyrinth fishes and their allies
合作研究:关键创新后的表型和谱系多样化:迷宫鱼及其盟友呼吸空气的多种进化途径
  • 批准号:
    2333683
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Continuing Grant
Collaborative Research: Phenotypic and lineage diversification after key innovation(s): multiple evolutionary pathways to air-breathing in labyrinth fishes and their allies
合作研究:关键创新后的表型和谱系多样化:迷宫鱼及其盟友呼吸空气的多种进化途径
  • 批准号:
    2333684
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Continuing Grant
CRII: CSR: Towards an Edge-enabled Software-Defined Vehicle Framework for Dynamic Over-the-Air Updates
CRII:CSR:迈向支持边缘的软件定义车辆框架,用于动态无线更新
  • 批准号:
    2348151
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Standard Grant
Smoldering coarse woody debris and air quality
阴燃粗木质碎片和空气质量
  • 批准号:
    IM240100016
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Mid-Career Industry Fellowships
Simulating Urban Air Pollution In The Lab
在实验室模拟城市空气污染
  • 批准号:
    MR/Y020014/1
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Fellowship
Development of a low-pressure loss air purification device using rotating porous media and a proposal for its use in ventilation systems
使用旋转多孔介质的低压损失空气净化装置的开发及其在通风系统中的使用建议
  • 批准号:
    24K17404
  • 财政年份:
    2024
  • 资助金额:
    $ 53.96万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了