DartCF: The Dartmouth Cystic Fibrosis Research Center

DartCF：达特茅斯囊性纤维化研究中心

基本信息

批准号：
10895148
负责人：
DEAN R MADDEN
金额：
$ 4.22万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10895148
关键词：
Acceleration Address Affect Antibiotics Archives Area Award Basic Science Bioinformatics Biology Biostatistics Core Cessation of life Chronic Clinical Clinical Research Coculture Techniques Collaborations Communities Complex Coupled Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Data Data Science Data Set Databases Development Diabetes Mellitus Disease Ecology Educational workshop Endowment Epithelium Evaluation Extramural Activities Faculty Fostering Foundations Functional disorder Funding Genetic Diseases Goals Immune Immune response Immunity Inflammatory Response Institution Intervention Investigation Liver diseases Longevity Lung Malnutrition Mediating Metabolic Microbe Mining Mission Modeling Monitor Mutation National Institute of Diabetes and Digestive and Kidney Diseases Organ Outcome Pancreatitis Pathogenesis Patients Pharmaceutical Preparations Pilot Projects Preclinical Drug Development Quality of life Research Research Personnel Resources Respiratory Tract Infections Services Signal Transduction Structure Symptoms System Therapeutic Tissues Training Translational Research Virulence Work antimicrobial base body system career development cohort commensal microbes community center complex data cystic fibrosis patients cystic fibrosis related diabetes data submission dysbiosis forging gastrointestinal gut dysbiosis gut microbes host-microbe interactions improved improved outcome innovation insight interest interoperability member microbial microbial community microbiome novel novel strategies novel therapeutic intervention novel therapeutics open data pathogenic microbe pre-clinical premature programs recruit synergism systemic inflammatory response tool translational study

Acceleration Address Affect Antibiotics Archives Area Award Basic Science Bioinformatics Biology Biostatistics Core Cessation of life Chronic Clinical Clinical Research Coculture Techniques Collaborations Communities Complex Coupled Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Data Data Science Data Set Databases Development Diabetes Mellitus Disease Ecology Educational workshop Endowment Epithelium Evaluation Extramural Activities Faculty Fostering Foundations Functional disorder Funding Genetic Diseases Goals Immune Immune response Immunity Inflammatory Response Institution Intervention Investigation Liver diseases Longevity Lung Malnutrition Mediating Metabolic Microbe Mining Mission Modeling Monitor Mutation National Institute of Diabetes and Digestive and Kidney Diseases Organ Outcome Pancreatitis Pathogenesis Patients Pharmaceutical Preparations Pilot Projects Preclinical Drug Development Quality of life Research Research Personnel Resources Respiratory Tract Infections Services Signal Transduction Structure Symptoms System Therapeutic Tissues Training Translational Research Virulence Work antimicrobial base body system career development cohort commensal microbes community center complex data cystic fibrosis patients cystic fibrosis related diabetes data submission dysbiosis forging gastrointestinal gut dysbiosis gut microbes host-microbe interactions improved improved outcome innovation insight interest interoperability member microbial microbial community microbiome novel novel strategies novel therapeutic intervention novel therapeutics open data pathogenic microbe pre-clinical premature programs recruit synergism systemic inflammatory response tool translational study

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项目摘要

In cystic fibrosis (CF), mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) unleash a cascade of clinical disorders, including chronic airway infections, systemic inflammation, microbial virulence, diabetes, malnutrition and liver disease. Great progress has been made in some areas of disease, and CFTR modulators provide dramatic benefits to some patients. Still, there is growing evidence of the interconnections among lung and gut dysbiosis and CF pathogenesis. As patients live longer, formerly rare symptoms are becoming more common. Thus, there is a pressing need to both understand and systematically treat the functional relationships between CFTR function, commensal and pathogenic microbes, metabolic states, and innate and acquired immune responses. Dartmouth has an interactive CF research team of 49 faculty members with extramural funding of $11.1M/year, studying epithelial biology, CFTR correction, host-microbe interactions, gut dysbiosis and immunity, as well as airway infections and antimicrobial strategies. The Dartmouth CF Research Center (DartCF) will build on progress made in the past year. We will deploy P30 and institutional funds to recruit new CF faculty, strengthen our research base, and foster interdisciplinary discovery. Our aims are: 1) to catalyze new research in CF basic and translational research in areas of interest to NIDDK; 2) to develop integrative strategies to understand and address CF pathobiology; 3) to create new research tools and support CF research through outstanding shared services; and 4) to build research capacity in CF locally, regionally, and nationally. We will focus P30 resources on 1) pioneering transparency and interoperability for CF datasets, 2) forging collaborations between CF and data-science researchers to mine these datasets for systems-level perspectives and 3) building on unique Dartmouth longitudinal patient cohorts to explore microbial community structure in the gut, host-microbe signaling, the effects of existing therapies, and implications for whole-body disease. A key theme is that dysbioses are interconnected, and that parallel investigations, coupled by powerful new data-science strategies can understand this complex underlying biology and reveal new therapeutic approaches. In parallel, we will leverage our research base to support early-stage preclinical target development. DartCF supports a variety of mechanisms. First, we fund a Pilot Project Project (P3) to develop new scientific opportunities in NIDDK-revelant areas and to recruit new faculty members to the Center. Second, we fund three scientific cores to support studies in CF: a Gastrointestinal Biology Core (GIBC), a Clinical and Translational Research Core (CTRC), and a CF Bioinformatics & Biostatistics Core (CF-BBC). Finally, we support an Enrichment and Research Administration Core (ERAC) to foster an interactive scientific community, sponsor retreats and courses, and track program progress. These efforts will identify new CF therapeutic opportunities, develop novel interventions, monitor the resulting changes body-wide, and track outcomes. DartCF will intensify the translation of research into improved CF outcomes at Dartmouth.

在囊性纤维化（CF）中，囊性纤维化跨膜电导调节剂（CFTR）的突变释放临床疾病的级联，包括慢性气道感染，全身性炎症，微生物毒力，糖尿病，营养不良和肝病。在某些疾病和CFTR中取得了巨大进展调节器为某些患者提供了巨大的好处。尽管如此，还有越来越多的互连证据在肺和肠道营养不良和CF发病机理中。随着患者的寿命更长，以前的罕见症状是变得越来越普遍。因此，迫切需要理解并系统地对待 CFTR功能，共生和致病性微生物，代谢状态以及先天和获得的免疫反应。达特茅斯（Dartmouth）有一个由49位教职员工组成的互动CF研究团队每年的校外资金为1,110万美元，研究上皮生物学，CFTR校正，宿主 - 微生物相互作用，肠道营养不良和免疫力以及气道感染和抗菌策略。达特茅斯CF 研究中心（DARTCF）将基于过去一年取得的进展。我们将部署P30和机构资金招募新的CF教师，加强我们的研究基础并促进跨学科发现。我们的目标是：1）在NIDDK感兴趣领域的CF基础研究和转化研究中催化新的研究； 2）到制定综合策略来理解和解决CF病理生物学； 3）创建新的研究工具和通过出色的共享服务支持CF研究； 4）在本地CF建立研究能力，在地区和全国范围内。我们将重点将P30资源集中在1）CF开创透明度和互操作性数据集，2）在CF和数据科学研究人员之间进行合作，以挖掘这些数据集的系统级别的观点和3）建立在独特的达尔茅斯纵向患者同类的基础上探索微生物肠道中的社区结构，宿主微型信号，现有疗法的影响以及对全身疾病。一个关键主题是互连的生物障碍是相互关联的，并进行了耦合的平行调查通过强大的新数据科学策略可以理解这种复杂的潜在生物学，并揭示新的治疗方法。同时，我们将利用研究基础来支持早期临床前目标发展。 DARTCF支持多种机制。首先，我们为开发试点项目（P3）提供资金 Niddk-Revelant地区的新科学机会，并招募新教师到该中心。第二，我们资助三个科学核心，以支持CF研究：胃肠道生物学核心（GIBC），临床和转化研究核心（CTRC）和CF生物信息学与生物统计学核心（CF-BBC）。最后，我们支持丰富和研究管理核心（ERAC），以培养互动的科学界，赞助者的撤退和课程，并跟踪计划的进度。这些努力将确定新的CF治疗机会，开发新颖的干预措施，监控所得的身体变化以及跟踪结果。 DARTCF将加强将研究转化为达特茅斯（Dartmouth）的CF结果的转化。