A CELL LINE FOR ANTIASTHMA DRUG DISCOVERY

描述（由申请人提供）：BioTechPlex公司（BioTechPlex）拟开发一种稳定的基因工程人支气管上皮细胞系，当选定的信号转导通路中的“哮喘特异性”调节蛋白被激活时，该细胞系可以产生可测量的信号。由于这种选择的调节蛋白的激活在过敏性气道中似乎是特异性的或至少是显著增强的，并且这种信号转导途径在哮喘患者气道的炎症和重塑中起着核心作用，因此具有增强的“哮喘特异性”信号转导机制的永生细胞系将提供一种适合于高通量筛选抗哮喘药物的新方法。在第一阶段，我们将构建转染稳定上皮细胞系所需的质粒和载体，以增强该调节蛋白的存在。我们将利用受体诱导的发光可报告片段的激活来评估这种转染的成功。在第二阶段，BioTechPlex将进一步开发该细胞系的能力。该项目将广泛影响哮喘、过敏和炎症的药物发现研究。它满足了NIH几个研究所的SBIR请求的需求和使命，包括：1)美国国家过敏和传染病研究所（NIAID）的哮喘，过敏和炎症项目，2)NHLBI对COPD和哮喘的理解和治疗；3)美国国家癌症研究所（NCI）基于与信号转导相互作用的分子靶点的新检测方法的发展。

DESCRIPTION (provided by applicant): BioTechPlex Corporation (BioTechPlex) proposes to develop a stable, genetically engineered human bronchial epithelial cell line that can produce a measurable signal when an "asthma specific" regulatory protein in a selected signal transduction pathway is activated. As activation of this selected regulatory protein appears to be specific or at least markedly enhanced in allergic airways, and this signal transduction pathway plays a central role in the inflammation and remodeling in airways in patients with asthma, an immortalized cell line with an enhanced "asthma-specific" signal transduction mechanism would provide a new assay suitable for high throughput screening for anti-asthmatic drugs. In Phase I, we will construct the necessary plasmids and vectors for the transfection of a stable epithelial cell line to enhance the presence of this regulatory protein. We will evaluate the success of this transfection using receptor-induced activation of a luminescent reportable moiety. In Phase II, BioTechPlex will further develop the capabilities of this cell line. This project will broadly impact drug discovery research in asthma, allergy and inflammation. It fulfills the needs and missions of the SBIR solicitations by several institutes of the NIH including: 1) the Asthma, Allergy and Inflammation program at the National Institutes of Allergy and Infectious Diseases (NIAID), 2) the understanding and treatment of COPD and asthma at NHLBI; and 3) the development of new assays based on molecular targets that interact with signal transduction at the National Cancer Institute, NCI.