A CELL LINE FOR ANTIASTHMA DRUG DISCOVERY

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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.