Pilot Project Program

本申请的首要目标是继续开发和加强达特茅斯囊性纤维化 研究中心（DartCF），在与NIDDK使命相关的领域复制我们以前成功的 在气道生物学和感染的CF相关研究的轨迹。试点项目计划（P3）是一个整体 我们战略的一部分。在P30资助的第一年，我们已经扩大了调查能力， 肠道中的宿主-微生物相互作用以及肠道生态失调对CF相关糖尿病和总体的影响 这些患者的全身性疾病和健康。第一批试剂、出版物和赠款提交是 从我们最初的一系列试点项目中脱颖而出。这反映了对以下方面的兴趣和核心支持日益增加： 在这些研究领域中，我们的开放RFA引出了18个高质量的NIDDK相关提案。从这些，我们有 选择了一组新的四个P3项目，所有项目都与CF的GI、全身或肝脏方面相关。我们的战略 建立我们的研究基地的现有优势，直接源于过去有效利用试验资金 ~15年。利用我们的经验和通过试点提高研究能力的出色记录 P3计划将（1）鼓励开发初步数据，以开辟新的研究 机会，完善假设，并加强建议，以争取校外支持，（2）加强 协作和跨学科的研究，以吸引目前的研究人员在达特茅斯，包括那些与 CF研究的记录和那些新的领域，并支持新招募的教师，（3）深化我们的水库 通过向医生科学家及其合作者提供资金， (4)核心多研究者赠款的提交，以及（5）通过以下方式支持专业发展 指导初级教员，包括基础科学家和内科科学家。这是一个行之有效的战略。在过去， 我们的CF基金会研究发展计划（RDP）和NIH生物医学研究中心 卓越奖（COBRE）将140万美元的试点资金转化为2290万美元的校外赠款支持 在过去的14年里。请注意，COBRE在2018年日落，CF试点与肺部主题有关 由RDP独家支持。利用这个模型作为框架，我们设计了一个包容性的 申请要求（RFA）和严格的多阶段审查程序，以授予P3赠款，以扩大我们的 研究肠道中宿主-微生物相互作用以及肠道生态失调对CF相关的影响的能力 糖尿病，根据三种机制：（1）指导初级教师的基本或翻译奖，（2） 跨学科合作基础或转化奖，以及（3）创新转化或临床 由MD或MD/PhD研究员领导的研究。所有这三个机制都促进跨学科、多领域、 研究者和临床相关研究。通过吸引现有和新的教师和支持 通过变革性研究，P3将直接增强DartCF的身份、影响和研究基础。

The overarching goal of this application is to continue to develop and strengthen the Dartmouth Cystic Fibrosis Research Center (DartCF), reproducing in areas relevant to NIDDK mission our previous successful trajectory of CF-related research in airway biology and infection. The Pilot Project Program (P3) is an integral part of our strategy. In our first year of P30 funding, we have already expanded our capacity to investigate host-microbe interactions in the gut and the impact of gut dysbiosis on CF-related diabetes and overall systemic disease and health of these patients. The first reagents, publications and grant submissions are emerging from our inaugural set of pilot projects. As a reflection of the growing interest in and Core support for these research areas, our open RFA elicited 18 high-quality NIDDK-relevant proposals. From these, we have selected a new set of four P3 projects, all in areas related to GI, systemic or liver aspects of CF. Our strategy to build the current strengths of our research base stems directly from effective use of pilot funds over the past ~15 years. Using our experience and outstanding track record of enhancing research capacity through pilot funds, the P3 Program will (1) encourage development of preliminary data to open up new research opportunities, refine hypotheses, and strength proposals to compete for extramural support, (2) enhance collaborative and interdisciplinary research to engage current researchers at Dartmouth, including those with a record of CF research and those new to the field, and support newly recruited faculty, (3) deepen our reservoir of translational and clinical research projects by providing funds to physician-scientists and their collaborators, (4) nucleate the submission of multi-investigator grants, and (5) support professional development through mentoring of junior faculty, including both basic and physician scientists. This is a proven strategy. In the past, our CF Foundation Research Development Program (RDP) and NIH Center for Biomedical Research Excellence (COBRE) awards leveraged $1.4M of pilot funding into $22.9M dollars of extramural grant support over the past 14 years. Note that the COBRE sunset in 2018 and that CF pilots related to pulmonary topics are supported exclusively by the RDP. Using this model as a framework, we have designed an inclusive Request for Applications (RFA) and rigorous multi-stage review procedure to award P3 grants to expand our capabilities to investigate host-microbe interactions in the gut and the impact of gut dysbiosis on CF-related diabetes, under three mechanisms: (1) Mentored Basic or Translational Awards for junior faculty, (2) interdisciplinary Collaborative Basic or Translational Awards, and (3) Innovative Translational or Clinical Studies led by an MD or MD/PhD faculty investigator. All three mechanisms foster interdisciplinary, multi- investigator, and clinically relevant research. By engaging existing and new faculty and supporting transformative research, the P3 will directly enhance the identity, impact, and research base of DartCF.