Biological Reagents and Infection Core

Biological Reagents and Infection Core Core 3 - ABSTRACT The overall goals of this Program Project Grant (P01) are to define the functional and molecular roles of caspase- 4/11 (CASP4/11) and RNA epigenetic modifications in SARS-CoV-2 pathobiology in the lung, brain, blood, and heart, to characterize the roles of CASP4/11 and RNA epigenetic modifications in SARS-CoV-2 innate and adaptive immunity, and develop new improved therapeutics against SARS-CoV-2 infection by targeting CASP4/11 and RNA modifications. In support of these goals, the Biological Reagents and Infection Core 3 (C3) brings together a team of investigators with expertise in animal models, virology, pathology, quality assurance, and scientific management to provide comprehensive, centralized biological reagents and animal challenge models for the Program. The goal of Core 3 is to develop key reagents, generate and maintain genetically engineered mouse lines, develop SARS-CoV-2 animal challenge models, and perform in vitro and in vivo assays in support of the Objectives of three Research Projects in this Program. Major tasks of Core 3 include: (i) generate high quality SARS-CoV-2 stocks for in vitro and in vivo experiments; (ii) generate and maintain genetically engineered mouse lines for in vivo infection; (iii) perform intranasal infections using the SARS-CoV-2 mouse challenge model, quantify SARS-CoV-2 viral loads and inflammatory cytokines in animal tissue after SARS-CoV-2 infection; and (iv) perform intranasal infections using the SARS-CoV-2 hamster challenge model. These comprehensive and centralized services will allow Project investigators to better, and more efficiently design and conduct experiments, analyze the results, ensure consistency, integrity, rigor and reproducibility, and more effectively utilize the animal models, the state-of-the-art instrumentation, and BSL3 and ABSL3 facilities. C3 will also closely collaborate with Administrative Core 1, Biostatistics Core 2, and Cell Core 4 to ensure that all proposed in vitro and in vivo experiments meet the Program's needs and goals.