Organoid Core B

类器官核心B

基本信息

批准号：
10178731
负责人：
CALVIN J KUO
金额：
$ 90万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-05 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10178731
关键词：
2019-nCoV 3-Dimensional Air Apical Architecture Biological Biological Models Biology COVID-19 COVID-19 pandemic Cancer cell line Cell Line Cells Cessation of life Chemicals Chemotactic Factors Chiroptera Collaborations Communicable Diseases Communication Containment Coronavirus Cryopreservation Disease Disease Outbreaks Enteral Epithelial Epithelial Cells Epithelium Etiology Funding Gastroenterology Goals Helicobacter pylori Histology Human Human body Immune Immunologic Memory In Vitro Incubators Infection Infectious Agent Intestines Liquid substance Lung Lung infections Methods Microbe Middle East Middle East Respiratory Syndrome Coronavirus Modeling Nature Organ Organism Organoids Pathology Physiological Population Property Public Health Reporting Rotavirus Infections Route SARS coronavirus Signal Transduction Stomach Structure of parenchyma of lung System Technology Therapeutic Tissues Tumor-infiltrating immune cells Viral Virus Diseases authority biosafety level 3 facility cell community gastrointestinal genetic manipulation global health human coronavirus human tissue improved in vitro Model in vivo infectious disease model mortality novel novel coronavirus pandemic disease pathogen physiologic model reconstitution respiratory screening self organization self-renewal single-cell RNA sequencing transmission process

项目摘要

ABSTRACT Primary human organoid models are an increasingly deployed platform for in vitro infectious disease modeling. The COVID-19 pandemic, engendered by the novel coronavirus SARS-CoV-2, represents a grave threat to public health and physiologic in vitro infection models are therefore urgently needed. This supplement request for U19AI116484, Stanford Cooperative Center for Novel, Alternative Model Systems for Enteric Diseases (Stanford NAMSED), requests funding to create new models for SARS-CoV-2 infection using novel human lung organoid technologies in collaboration with Dr. Ralph Baric at UNC, a recognized coronavirus authority. These studies exploit SARS-CoV-2 infection of organoids using a feeder-free, chemically defined human lung organoid system (Calvin Kuo lab), lung organoids with integrated immune components (Calvin Kuo), methods for robust apical-basal inversion of lung organoid polarity (Manuel Amieva), BSL3 single cell RNA-seq (Catherine Blish) and SARS-CoV-2-GFP indicator strains and BSL3 facilities (Ralph Baric). The SARS-CoV-2 infection of lung organoids will occur in BSL3 containment at both UNC and Stanford to compare apical versus basal infection routes, document how epithelial infection initiates secondary immune responses, and overall generate improved 3D physiological models of SARS-CoV-2-GFP infection relevant to therapeutics screening.

抽象的原发性人体器官模型是越来越部署的体外传染病建模平台。由小说冠状病毒SARS-COV-2引起的COVID-19大流行代表了对因此，迫切需要公共卫生和生理体外感染模型。此补充要求对于U19AI116484，斯坦福（斯坦福 Organoid Technologies与公认的冠状病毒管理局UNC的Ralph Baric博士合作。这些研究使用无馈物，化学定义的人类肺器官来利用类器官SARS-COV-2感染器官系统（Calvin Kuo Lab），具有综合免疫成分（Calvin Kuo）的肺器官，可靠的方法肺器官极性（Manuel Amieva），BSL3单细胞RNA-Seq（Catherine Blish）的顶端基质反转和SARS-COV-2-GFP指示器应变和BSL3设施（Ralph Baric）。肺的SARS-COV-2感染类器官将在UNC和Stanford的BSL3遏制中发生，以比较顶端感染与基础感染路线，记录上皮感染如何启动次级免疫反应，并总体产生改善与治疗筛查有关的SARS-COV-2-GFP感染的3D生理模型。