The Organoid and Cell Culture Core

类器官和细胞培养核心

基本信息

批准号：
10612964
负责人：
Hiroshi Nakagawa
金额：
$ 16.83万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-30 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612964
关键词：
3-Dimensional Adult Bioinformatics Biological Models CRISPR screen CRISPR/Cas technology Catalogs Cell Communication Cell Culture System Cell Culture Techniques Cell Line Cells Childhood Clinical Coculture Techniques Collaborations Communities Consult Cryopreservation Data Development Digestive System Disorders Disease Disease model Doctor of Philosophy Drug Screening Education Educational workshop Emerging Technologies Epithelial Cells Equipment Experimental Designs Feedback Gene Expression Genes Genome Grant Growth Guide RNA Hepatobiliary Homeostasis Human Human Cell Line Human Resources Internet Laboratories Leadership Lentivirus Vector Libraries Link Liver diseases Longevity Measures Mediating Medicine Mission Modeling Molecular Morphology Mouse Cell Line Mus Mycoplasma Mycoplasma Infections Organoids Pancreas Pancreatic Diseases Patients Protocols documentation Quality Control RNA Interference Reagent Reproducibility Research Research Personnel Science Scientist Series Services Standardization Surveys System Techniques Technology Testing Tissues Training Training and Education Transgenic Mice Translational Research Translations Universities Visualization Work bioimaging cell repository cost effective cost effective measures cost effectiveness drug testing experimental study expression vector gastrointestinal genetically modified cells high resolution imaging induced pluripotent stem cell member new technology novel operation pediatric patients pre-clinical programs repository single cell analysis tool transcriptome sequencing

项目摘要

SUMMARY The Organoid and Cell Culture Core (OCCC) will contribute to the mission of the Columbia University Digestive and Liver Disease Research Center (CU-DLDRC) by serving members’ needs related to human and murine cell culture systems for modeling of gastrointestinal, hepatobiliary and pancreatic diseases. These systems include primary culture, genetically-engineered cell lines, spheroids and organoids as well as 3D co-culture. OCCC platforms will benefit the majority of clinical and basic CU-DLDRC investigators, providing powerful tools to study epithelial cells and their interactions in digestive homeostasis and disease, the central theme of the CU-DLDRC. Directed by Drs. Hiroshi Nakagawa, MD, PhD and Kelley Yan, MD, PhD, two scientists with long-standing complementary expertise in advanced cell culture and organoids, the OCCC will provide services, technologies, quality control and cost-effectiveness to the CU-DLDRC investigators, including the Pilot and Feasibility grant recipients. The OCCC will provide a rich repository of cell lines and human and mouse organoids that are well annotated for identity, passage number, and Mycoplasma infection-free status, thereby providing quality control, rigor and reproducibility. The OCCC will also assist CU-DLDRC investigators to generate 3D organoids from their human and mouse tissues as well as from inducible pluripotent stem (iPS) cells, to analyze growth, morphology, gene expression, and cell-cell interactions via co-culture experiments. The OCCC will integrate advanced cell culture technologies for manipulating genome and gene expression via CRISPR/Cas9, RNA interference, and inducible retroviral/lentiviral gene expression vectors in cell and organoid-based systems. These approaches are further enhanced by coordinated multi-core workflows with the Clinical Biospecimen and Research Core for patient- and disease-specific organoids; with the Bioinformatics and Single Cell Analysis Core for the plate-RNAseq-based CRISPR and drug screens; and with the Bioimaging Core for functional visualization of cells and organoids. The OCCC will promote the mission of the CU-DLDRC through the following interrelated Specific Aims: To provide CU-DLDRC members and their laboratories with cell lines, advanced cell culture platforms and technologies (Aim 1); to build and expand unique CU-DLDRC and national repositories of disease- specific human and mouse 3D organoid libraries (Aim 2); and to enhance the technical capabilities of new and established CU-DLDRC investigators through training on cell and organoid culture models and as well as educational seminars on novel developments (Aim 3). The OCCC will be highly utilized with 71% of CU-DLDRC members indicating use, most of them use of multiple OCCC services. In summary, the OCCC will provide highly efficient and cost-effective services and unique models that do not currently exist in CU-DLDRC members’ laboratory and therefore constitute significant benefits. Through its services, OCCC will stimulate translational science and collaborations in the CU-DLDRC and contribute to its mission to promote digestive disease science.

概括器官和细胞培养核心（OCCC）将有助于哥伦比亚大学消化和肝病研究中心（CU-DLDRC）通过满足与人类和鼠类细胞有关的成员需求用于建模胃肠道，肝胆和胰腺疾病的培养系统。这些系统包括原发性培养，遗传工程细胞系，球体和器官以及3D共培养。 OCCC 平台将使大多数临床和基本CU-DLDRC调查人员受益，提供强大的工具来研究上皮细胞及其在消化体稳态和疾病中的相互作用，这是Cu-DLDRC的中心主题。由Drs执导。医学博士Nakagawa Hiroshi Nakagawa和MD，PhD的Kelley Yan，两位科学家 OCCC在高级细胞培养和器官方面的完全专业知识将提供服务，技术， CU-DLDRC调查人员的质量控制和成本效益，包括飞行员和可行性赠款收件人。 OCCC将提供丰富的细胞系以及人类和小鼠类器官的存储库注释以确认，通过数量和支原体无感染状态，从而提供质量控制，严格和可重复性。 OCCC还将协助Cu-dldRC研究人员从它们的人体和小鼠组织以及诱导多能茎（IPS）细胞，以分析生长，通过共培养实验的形态，基因表达和细胞 - 细胞相互作用。 OCCC将集成通过CRISPR/CAS9（RNA）操纵基因组和基因表达的晚期细胞培养技术干扰和可诱导的逆转录病毒/慢病毒基因表达载体在细胞和基于器官的系统中。通过与临床生物测量和协调的多核工作流程进一步增强了这些方法患者和疾病特异性器官的研究核心；使用生物信息学和单细胞分析核心用于基于板块的rnaseq的CRIS和药物筛选；并具有用于功能可视化的生物影像芯细胞和类器官。 OCCC将通过以下相互关联来促进Cu-dldrc的使命具体目的：为CU-DLDRC成员及其实验室提供细胞系，高级细胞培养平台和技术（AIM 1）；建立和扩展独特的Cu-dldrc和疾病的国家存储库 - 特定的人和小鼠3D器官库（AIM 2）；并增强新的和通过培训细胞和器官培养模型以及有关新事态发展的教育半货人（AIM 3）。 OCCC将高度利用与71％的Cu-DLDRC一起使用表明使用的成员，其中大多数使用多个OCCC服务。总而言之，OCCC将高度提供 CU-DLDRC成员目前不存在的高效且具有成本效益的服务以及独特的模型实验室，因此构成了巨大的好处。通过其服务，OCCC将刺激翻译 Cu-DLDRC的科学与合作，并为促进消化系统疾病科学的任务做出了贡献。