DARTMOUTH COL COBRE: P2: REGULATION OF ENDOCYTIC TRAFFICKING OF CFTR

描述(由申请人提供)： 这项申请的目标是增加新罕布夏州在获得NIH资金方面具有竞争力的研究人员的数量，并建立一个将在五年内获得全国认可和独立的肺生物学中心。基于达特茅斯和基恩州立学院(KSC)现有的协作和多学科教员以及该州其他调查人员的核心，科布雷基金将提供资源，以发展初级教员和获得中心地位所需的基础设施。将通过五种方式促进教师的成长和发展：1)招聘三名终身教职教师：两名在达特茅斯，一名在基恩州立学院；2)在指导下发展四名已在达特茅斯的初级研究人员，一名已在基恩州立学院；3)达特茅斯、基恩州立学院与提供达特茅斯没有的专业知识的本州研究人员之间的联系；以及5)通过研究项目和相关的管理和蛋白质组核心进行协同科学合作。在现任达特茅斯大学肺生物学项目主任斯坦顿博士的领导下，加上大量的机构承诺，我们相信现有的研究人员基础将随着科布雷的资助而扩大和成熟，建立一个由在获得NIH资金方面将更具竞争力的教职员工组成的中心，从而加强国家的研究资助组合。这五个研究项目展示了一个中心的多学科方法，并由肺生物学和囊性纤维化(CF)、癌症和肺损伤以及蛋白质组学等疾病的共同主题联系在一起。项目1将研究CF肺中生物膜的形成。项目2将研究？F508-CFTR贩运。项目3研究了调控CFTR功能和运输的CFTR-PDZ蛋白质相互作用的结构基础。项目1-3的最终目标是阐明慢性阻塞性肺疾病的细胞机制，它们在方法上是互补的。在项目4中，主要目标是确定可用于确定暴露于空气污染物与癌症、阻塞性呼吸道疾病和哮喘发病率增加之间的因果关系的生物标志物。项目5的目标是使用地理信息系统和病例参考方法的多层次方法来研究肺癌的环境流行病学。这些项目将共同促进我们项目的发展，并有助于更好地了解肺部疾病背后的细胞和分子机制。我们计划的长期目标是进行转化性研究，以开发肺部疾病的新疗法和治疗方法。

DESCRIPTION (provided by applicant): The goals of this application are to increase the number of investigators in New Hampshire who are competitive in securing NIH funding, and to establish a Lung Biology Center that will be nationally recognized and free standing in five years. Based on a core of existing collaborative and multidisciplinary faculty at Dartmouth and Keene State College (KSC) along with other investigators in the State, COBRE funding will provide resources to develop junior faculty and infrastructure necessary to attain Center status. Faculty growth and development will be facilitated in five ways: 1) recruitment of three tenure-track faculty: two at Dartmouth, and one at Keene State College; 2) mentored development of four junior investigators already at Dartmouth, and one already at Keene State College; 3) linkage between Dartmouth, Keene State College and investigators in the State who provide expertise not available at Dartmouth; and 5) synergistic scientific collaboration through the research projects and associated administrative and proteomic cores. Under the leadership of Dr. Stanton, the current Director of the Lung Biology Program at Dartmouth, together with substantial institutional commitments, we are confident that the existing base of investigators will expand and mature with COBRE funding to an established Center, comprised of faculty who will be more competitive in obtaining NIH funding, and thereby enhance the research grant portfolio of the State. The five research projects exhibit a multidisciplinary approach characteristic of a Center and are connected by the common themes of lung biology and disease including cystic fibrosis (CF), cancer and lung injury as well as proteomics. Project 1 will examine biofilm formation in the CF lung. Project 2 will study ?F508-CFTR trafficking. Project 3 examines the structural basis of the CFTR-PDZ protein interactions that regulate the function and trafficking of CFTR. The ultimate goals of Projects 1-3, which are complementary in approach, are to elucidate the cellular mechanisms of lung disease in CF. In Project 4 the major goal is to identify biomarkers that can be used to determine causal relationships between exposure to airborne pollutants and increased incidence of cancer, obstructive airway disease and asthma. The goal of Project 5 is to use a multilevel approach using Geographic Information Systems and case-reference methods to study the environmental epidemiology of lung cancer. Together these projects will contribute to the growth of our Program and to a better understanding of the cellular and molecular mechanisms that underlie lung disease. The long-term goal of our Program is to conduct translational studies to develop new treatments and cures for lung disease.