Understanding the regulation of airway epithelial chloride channels

拟议的研究计划旨在更深入地了解食盐的一种成分氯化物在整个呼吸道(或气管)内的细胞中的运动。被称为通道的蛋白质允许氯化物从细胞外移动到呼吸道表面。氯化物用它吸水，从而适当地补充呼吸道的水分，保护它免受感染。该计划的长期目标是发现和确定在正常和疾病的呼吸道细胞中参与氯离子运动的通道和相关蛋白的作用。在接下来的五年中，将讨论两个短期目标，即调节氯化物运动的一种特定蛋白质的作用和行动。最初，特定蛋白质作用于的通道的特定基因将被识别。其次，将确定特定蛋白质如何在已识别的通道结构中相互作用，从而确定一种现象的机制，这一现象在15年多的时间里一直无法解释。两名研究生将参与这项研究，并将在分子、生化和电生理学技术方面接受广泛的培训，这些技能是制药业雇主非常希望和追捧的。他们毕业后的专业知识将扩大他们潜在的职业范围，并提高加拿大研究的声誉。最后，通过这项研究获得的知识将有助于更好地了解影响加拿大人的呼吸系统疾病，如囊性纤维化、哮喘和慢性阻塞性肺疾病(COPD)，并将导致创新治疗的开发。

The proposed research program is aimed at developing a more in-depth knowledge of the movement of chloride, a component of table salt, in cells lining the entire airway (or windpipe). Proteins called channels allow the movement of chloride out of cells and onto the airway surface. The chloride pulls water with it, thus properly hydrating the airway and protecting it against infection. The program's long-term goal is to discover and define the contribution of channels and related proteins involved in chloride movement in both normal and diseased airway cells. Two short term objectives will be addressed over the next five years regarding the role and action of one specific protein that modulates chloride movement. Initially, the specific gene of the channel that the specific protein acts upon will be identified. Secondly, how the specific protein interacts within the identified channel's structure will be determined, thereby defining a mechanism for a phenomenon that has eluded explanation for over 15 years. Two graduate students will be involved in this research and will receive extensive training in molecular, biochemical, and electrophysiology techniques, skills which are highly desirable and sought after by pharmaceutical industry employers. Their expertise upon graduation will expand their potential range of careers and enhance the reputation of research in Canada. Finally, the knowledge gained through this research will lead to a better understanding of respiratory diseases that impact Canadians, such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease (COPD), and will lead to the development of innovative treatments.