Organoid Core B

摘要 原生人体器官模型是一种越来越多的用于体外传染病建模的平台。 由新型冠状病毒SARS-CoV-2引发的新冠肺炎大流行对 因此，迫切需要公共卫生和生理学的体外感染模型。这项补充要求 对于U19AI116484，斯坦福大学肠道疾病新型替代模型系统合作中心 (Stanford NAMSED)，要求提供资金，使用新的人类肺创建新的SARS-CoV-2感染模型 与公认的冠状病毒权威机构北卡罗来纳大学的拉尔夫·巴里奇博士合作开发有机化合物技术。这些 使用化学定义的无饲养器的人肺有机物质研究SARS-CoV-2对有机物质的感染 系统(Calvin Kuo实验室)、具有集成免疫成分的肺有机体(Calvin Kuo)、健壮方法 肺器官的根尖-基底反转(曼努埃尔·阿米耶娃)，BSL3单细胞RNA-SEQ(凯瑟琳·布利什) 和SARS-CoV-2-GFP指示株和BSL3设施(Ralph Baric)。SARS-CoV-2肺部感染 在北卡罗来纳大学和斯坦福大学，BSL3安全壳中都会出现有机物，以比较根尖感染和基底感染 途径，记录上皮细胞感染如何启动二次免疫反应，并总体产生改善 与药物筛选相关的SARS-CoV-2-GFP感染的三维生理模型

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.