Gastrointestinal Biology Core

胃肠生物学核心

基本信息

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
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/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

项目摘要

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）的使命是进步基础科学以及翻译和发现与胃肠道（GI）疾病有关的研究研究。该核心的中心服务是提供广泛的模型系统，在选择模型和分析方法方面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中的胃肠道疾病，包括配对的WT和CF小鼠和人类 3D肠癌，2D单层，源自肠道类器官，肠道芯片系统，工程设计细胞系，转化试剂和小鼠模型。人类GI细胞模型已在与临床研究翻译核心（CRTC）合作，该核心提供了活检组织样本和 GI临床细菌分离株。 GIBC将促进DARTCF调查人员的持续研究，我们的合作者在其他CF研究中心，以及DARTCF试点项目计划支持的试点研究。核心意愿还可以根据需要协助入门或开发新颖方法论中心成员和试点项目获奖者。 GIBC的著名服务包括：（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器官和2D 来自小鼠和人类的器官衍生的单层，利用其在共培养模型中的专业知识来研究这些模型与胃肠道细菌之间的相互作用，启动了肠道芯片模型，并以此为特征从CF和非CF儿童的粪便获得的30种细菌分离株以及内镜抽吸物（CTRC）; （2）单细胞-RNA测序，其他分子技术的专业知识和GI的表征类器官，与CF生物信息学和生物统计学核心（CF-BBC）一起工作；（3）支持功能研究包括3D GI类器官的福斯科林诱导的肿胀测定法和电生理研究 2D器官单层。在支持的第一年，我们对鼠标和人类3D进行了FIS分析结肠癌和在2D类器官单层上进行的室内实验；（4）支持小鼠的研究在CF中研究胃肠道疾病的模型；（5）与行业协调开发新的多器官疗法与CF相关，以及（6）使用GI微生物共培养器官模型和小鼠模型的培训向中心的成员以及地区，全国和世界各地的调查人员致敬。 GIBC 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。该核心由Andrew C. Vail微生物学和免疫学教授Bruce Stanton博士共同指导以及微生物学和免疫学教授Deborah Hogan博士。斯坦顿博士和霍根博士有涵盖CF，肾脏生理学，细胞和分子生物学，蛋白质运输的互补专业知识，微生物学，微生物生态学，宿主 - 病原体和多数菌相互作用，动物研究和细胞文化促进了该核心核心能力的发展。