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Principal Investigator: Jianrong Li
Organization: OHIO STATE UNIVERSITY
Fiscal Year: 2024
Award: $376,173
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Anesthesia><Anesthesia procedures><Animal Model><Animal Models and Related Studies><Animals><Assay><B.1.1.529><B.1.617.2><BSL-3 facility><BSL3 facility><Bioassay><Biologic Sciences><Biological><Biological Assay><Biological Sciences><Bioscience><Biostatistics Core><Blood><Blood Coagulation Disorders><Blood Reticuloendothelial System><Body Weight Changes><Brain><Brain Nervous System><Breeding><COVID-19 infection><COVID-19 therapeutics><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Caspase><Caspase Gene><Caspase Inhibitor><Cell Body><Cell-Death Protease><Cells><CoV-2><CoV2><Coagulation Disorder><Coagulopathy><Collaborations><Conchae Nasales><Cricetinae><Cysteine Endopeptidases><Cysteine Protease><Cysteine Proteinases><Cytokines and Inflammatory Response><Delta variant><Detection><EC 2.1.1><ELISA><Encephalon><Ensure><Enzyme-Linked Immunosorbent Assay><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Euthanasia><GEM model><GEMM model><Genetically Engineered Mouse><Genome><Genotype><Goals><Golden Hamsters><Golden Syrian Hamsters><Hamsters><Hamsters Mammals><Heart><Histology><Human><ICE-like protease><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><In Vitro><Infection><Inflammasome><Inflammatory><Inflammatory Response Pathway><Innate Immunity><Investigators><Isoflurane><KO mice><Kidney><Kidney Urinary System><Knock-out Mice><Knockout Mice><Lead><Life Sciences><Liver><LoxP-flanked allele><Lung><Lung Respiratory System><Mediating><Mercy Killing><Mesocricetus auratus><Methyltransferase><Mice><Mice Mammals><Modeling><Modern Man><Modification><Molecular><Murine><Mus><Nasal><Nasal Passages Nose><Nasal turbinate bone structure><Native Immunity><Natural Immunity><Non-Polyadenylated RNA><Non-Specific Immunity><Nonspecific Immunity><Nose><Null Mouse><Ohio><Omicron variant><Organ><P01 Mechanism><P01 Program><Pathology><Pb element><Plaque Assay><Procedures><Program Project Grant><Program Research Project Grants><Qualifying><R-Series Research Projects><R01 Mechanism><R01 Program><RNA><RNA Gene Products><Reagent><Recombinants><Reproducibility><Research Grants><Research Personnel><Research Program Projects><Research Project Grants><Research Projects><Researchers><Respiratory System, Nose, Nasal Passages><Ribonucleic Acid><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 B.1.1.529><SARS-CoV-2 B.1.617.2><SARS-CoV-2 delta><SARS-CoV-2 infection><SARS-CoV-2 omicron><SARS-CoV-2 omicron variant><SARS-CoV-2 therapeutics><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 therapeutics><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Services><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 therapeutics><Severe acute respiratory syndrome related corona virus 2><Standardization><Symptoms><Syrian Hamsters><Testing><Therapeutic Agents><Therapeutic Effect><Tissue Extracts><Titrations><Transgenic Organisms><Turbinates><Universities><Veterinarians><Veterinary Medicine><Viral Burden><Viral Genome><Viral Load><Viral Load result><Virus><Weight Change><Wuhan coronavirus><adaptive immunity><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><animal tissue><biologic><biosafety level 3 facility><bleeding disorder><bronchial epithelium><clotting disorder><college><collegiate><coronavirus disease 2019 infection><coronavirus disease 2019 therapeutics><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19 virus><cystein protease><cystein proteinase><cysteine endopeptidase><cytokine><design><designing><efficacy testing><enzyme linked immunoassay><epigenetically><expectation><experiment><experimental research><experimental study><experiments><floxed><floxed allele><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><genetically engineered mouse model><genetically engineered murine model><hCoV19><heavy metal Pb><heavy metal lead><hepatic body system><hepatic organ system><human disease><improved><in vivo><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><instrumentation><methylase><model of animal><mouse genome><nCoV2><omicron variant of COVID-19><omicron variant of SARS-CoV-2><post SARS-CoV-2 infection><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><programs><pulmonary><quality assurance><renal><respiratory virus><severe acute respiratory syndrome coronavirus 2 B.1.1.529><severe acute respiratory syndrome coronavirus 2 B.1.617.2><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><social role><therapeutics against COVID-19><therapeutics against SARS-CoV-2><therapeutics against SARS-coronavirus-2><therapeutics against Severe acute respiratory syndrome coronavirus 2><therapeutics against coronavirus disease 2019><therapeutics for novel coronavirus><transgenic><transmethylase><variants of concern><virology><virus genome>