Gastrointestinal Biology Core

胃肠生物学核心

• 批准号: 10001761
• 负责人: Bruce A. Stanton
• 金额: $ 21.97万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 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/10001761
• 关键词: 16S ribosomal RNA sequencing; 3-Dimensional; Affect; Animal Experimentation; Aspirate substance; Bacteria; Basic Science; Bioinformatics; Biological; Biological Assay; Biological Models; Biological Response Modifier Therapy; Biology; Biometry; Biopsy; Biostatistics Core; Cell Culture Techniques; Cell Line; Cell model; Cells; Cellular biology; Child; Clinical; Clinical Research; Coculture Techniques; Collaborations; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Development; Doctor of Philosophy; Ecology; Educational workshop; Electrophysiology (science); Engineering; Faculty; Feces; Forskolin; Fostering; Gastrointestinal Diseases; Genomics; Gills; Goals; Gram-Negative Bacteria; Human; Immunology; In Vitro; Industry; Inflammation; Innate Immune Response; Intestines; Ions; Kidney; Longevity; Methodology; Methods; Microbe; Microbiology; Mission; Modeling; Molecular; Molecular Biology; Mus; Mutation; Organoids; Permeability; Pharmaceutical Preparations; Physiology; Pilot Projects; Probiotics; Publishing; Quantitative Reverse Transcriptase PCR; Reagent; Research; Research Personnel; Resistance; Science; Scientist; Services; Swelling; System; Techniques; Testing; Therapeutic; Tissue Sample; Tissues; Training; Training Support; Transfection; Translational Research; Universities; Work; cystic fibrosis mouse; cystic fibrosis patients; dysbiosis; experimental study; gastrointestinal; gastrointestinal bacteria; gastrointestinal epithelium; gut microbiome; industry partner; member; metabolomics; microbial; microbiome; monolayer; mouse model; novel; novel therapeutics; organ on a chip; pathogen; personalized medicine; professor; programs; protein transport; single-cell RNA sequencing; tool; tool development; transcriptome sequencing

The mission of the Gastrointestinal Biology Core (GIBC) is to advance basic science, as well as translational and discovery studies relevant to gastrointestinal (GI) disease in CF. A central service of this Core is to offer a broad spectrum of model systems, expertise in the selection of models and analytical approaches, and the introduction or development of new model systems to facilitate GI research by DartCF scientists. The GIBC has implemented a suite of models to study GI disease in CF, including paired WT and CF mouse and human 3D intestinal organoids, 2D monolayers derived from intestinal organoids, Gut-On-A-Chip systems, engineered cell lines, transformation reagents and mouse models. The human GI cell models have been developed in collaboration with the Clinical Research Translation Core (CRTC), which provided biopsy tissue samples and GI clinical bacterial isolates. The GIBC will facilitate ongoing studies of DartCF investigators, our collaborators at other CF Research Centers, and pilot studies supported by the DartCF Pilot Project Program. The Core will also assist in the onboarding or development of novel methodologies, as needed, to advance the science of Center members and Pilot Project awardees. Notable services of the GIBC include: (1) Support for GI host- microbe co-culture studies. In the first year of support the GIBC has implemented 3D organoids and 2D organoid-derived monolayers from mice and humans, leveraged its expertise in co-culture models to study interactions between these models and GI bacteria, initiated the Gut-On-A-Chip model, and characterized over 30 bacterial isolates obtained from the stool of CF and non-CF children and from endoscopic aspirates (CTRC); (2) Expertise in single cell-RNA-sequencing, other molecular techniques, and characterization of GI organoids, working with the CF Bioinformatics and Biostatistics Core (CF-BBC); (3) Support for functional studies including forskolin-induced swelling assays (FIS) of 3D GI organoids, and electrophysiological studies of 2D organoid monolayers. In the first year of support we performed FIS assays on mouse and human 3D colonoids, and Ussing chamber experiments on 2D organoid monolayers; (4) Support for studies on mouse models to study GI disease in CF; (5) Coordination with industry to develop new multi-organ therapeutics relevant to CF, and (6) Training in the use of GI microbe-host co-culture organoid models and mouse models to members of the Center as well as investigators regionally, nationally, and around the world. The GIBC launched in 2018 to meet the research needs of DartCF faculty, and to facilitate GI research at Dartmouth. This Core is co-directed by Bruce Stanton, PhD, the Andrew C. Vail Professor of Microbiology and Immunology and Deborah Hogan, PhD, Professor of Microbiology and Immunology. Dr. Stanton and Dr. Hogan have complementary expertise covering CF, kidney physiology, cell and molecular biology, protein trafficking, microbiology, microbial ecology, host-pathogen and polymicrobial interactions, animal research, and cell culture, which has fostered the development of the central capabilities of this Core.

胃肠生物学核心 (GIBC) 的使命是推进基础科学以及转化 与 CF 胃肠道 (GI) 疾病相关的发现研究。该核心的核心服务是提供 广泛的模型系统、模型选择和分析方法的专业知识以及 引入或开发新的模型系统，以促进 DartCF 科学家的 GI 研究。 GIBC 已经实施了一套模型来研究 CF 胃肠道疾病，包括配对的 WT 和 CF 小鼠以及人类 3D 肠道类器官、源自肠道类器官的 2D 单层、Gut-On-A-Chip 系统、工程设计 细胞系、转化试剂和小鼠模型。人类胃肠道细胞模型已于 与临床研究翻译核心 (CRTC) 合作，提供活检组织样本和 胃肠道临床细菌分离株。 GIBC 将促进 DartCF 研究人员（我们的合作者）正在进行的研究 其他 CF 研究中心以及 DartCF 试点项目计划支持的试点研究。核心将 还根据需要协助引入或开发新方法，以推进科学 中心成员和试点项目获奖者。 GIBC 的著名服务包括： (1) 对 GI 主机的支持 微生物共培养研究。在支持的第一年，GIBC 实施了 3D 类器官和 2D 来自小鼠和人类的类器官衍生单层细胞，利用其在共培养模型方面的专业知识进行研究 这些模型与胃肠道细菌之间的相互作用，启动了芯片上肠道模型，并通过 从 CF 和非 CF 儿童的粪便以及内窥镜抽吸物中分离出 30 种细菌 （CTRC）； (2) 单细胞 RNA 测序、其他分子技术和 GI 表征方面的专业知识 类器官，与 CF 生物信息学和生物统计学核心 (CF-BBC) 合作； (3)功能支持 研究包括 3D GI 类器官毛喉素诱导肿胀测定 (FIS) 和电生理学研究 二维类器官单层。在支持的第一年，我们对小鼠和人类 3D 进行了 FIS 检测 类器官和 2D 类器官单层的 Ussing 室实验； (4) 支持小鼠研究 研究 CF 胃肠道疾病的模型； (5) 与业界协调开发新的多器官疗法 与CF相关，以及（6）胃肠道微生物-宿主共培养类器官模型和小鼠模型的使用培训 向中心成员以及区域、国家和世界各地的研究人员提供信息。 GIBC 于 2018 年推出，旨在满足 DartCF 教师的研究需求，并促进达特茅斯的 GI 研究。 该核心由微生物学和免疫学教授 Andrew C. Vail 教授 Bruce Stanton 博士共同指导 和黛博拉霍根博士，微生物学和免疫学教授。斯坦顿博士和霍根博士 互补的专业知识涵盖 CF、肾脏生理学、细胞和分子生物学、蛋白质运输、 微生物学、微生物生态学、宿主-病原体和多种微生物相互作用、动物研究和细胞 文化，促进了该核心核心能力的发展。