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.

胃肠道生物学核心（GIBC）的使命是推进基础科学，以及转化 和CF中胃肠道（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，选择模型和分析方法的专业知识， 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中的GI疾病，包括配对的WT和CF小鼠和人类 3D肠类器官，源自肠类器官的2D单层，肠芯片系统，工程化 细胞系、转化试剂和小鼠模型。人类GI细胞模型已经在 与临床研究翻译中心（CRTC）合作，提供活检组织样本， GI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 在其他CF研究中心，并由DartCF试点项目计划支持的试点研究。芯会 此外，还应根据需要协助开展或开发新的方法，以推进 中心成员和试点项目获奖者。GIBC的主要服务包括：（1）支持GI主机- 微生物共培养研究。在支持的第一年，GIBC已经实施了3D类器官和2D 来自小鼠和人类的类器官衍生单层，利用其在共培养模型中的专业知识来研究 这些模型与GI细菌之间的相互作用，启动了肠道芯片模型，并在 从CF和非CF儿童的粪便和内窥镜抽吸物中获得30株细菌分离株 （CTRC）;（2）单细胞RNA测序、其他分子技术和GI表征的专业知识 类器官，与CF生物信息学和生物统计学核心（CF-BBC）合作;（3）支持功能 研究包括3D GI类器官的毛喉素诱导肿胀试验（FIS）和电生理学研究 2D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分析， （4）支持小鼠类器官单层的研究; 研究CF中GI疾病的模型;（5）与行业合作开发新的多器官治疗方法 与CF相关，以及（6）使用GI微生物-宿主共培养类器官模型和小鼠模型的培训 向中心成员以及区域、国家和世界各地的调查人员提供信息。GIBC 该计划于2018年启动，以满足DartCF教师的研究需求，并促进达特茅斯的GI研究。 这个核心是共同导演布鲁斯斯坦顿，博士，安德鲁C。微生物学和免疫学Vail教授 和Deborah Hogan博士，微生物学和免疫学教授。斯坦顿博士和霍根博士 补充专业知识，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-病原体和多微生物相互作用，动物研究和细胞 文化，它促进了这一核心核心能力的发展。