Core D - Genomics

核心 D - 基因组学

• 批准号: 10513939
• 负责人: Alexander L Greninger
• 金额: $ 284.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-16 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10513939
• 关键词: 2019-nCoV; Accreditation; Alleles; Animals; Antiviral Agents; Antiviral resistance; Binding Sites; Biochemical; Bioinformatics; Biological Assay; COVID-19 pandemic; Clinical Trials; Consensus; Country; DNA-Directed RNA Polymerase; Data; Development; Ensure; Enterovirus; Evolution; FDA Emergency Use Authorization; Family; Genbank; Gene Frequency; Genomics; Genotype; Herpesviridae; Human; In Vitro; Influenza A virus; Informatics; Infrastructure; Laboratories; Libraries; Measures; Metagenomics; Molecular; Mutate; Mutation; Nucleic Acids; Nucleotides; Oligonucleotides; Oral; Phase; Polymerase; Protocols documentation; Quality Control; RNA; RNA Viruses; Recovery; Reproducibility; Research Project Grants; Resistance; Resistance development; Resolution; SARS-CoV-2 genome; Scientific Inquiry; Sequence Read Archive; Shotguns; Specimen; Speed; Structure; Testing; Therapeutic Trials; Time; Universities; Vaccines; Variant; Viral; Viral Genome; Viral Load result; Viral Proteins; Virus; Visualization; Washington; Work; anti-viral efficacy; antiviral drug development; base; deep sequencing; experience; experimental study; genome sequencing; human coronavirus; in vivo; laboratory facility; longitudinal analysis; longitudinal design; medical countermeasure; molnupiravir; novel; pandemic disease; parainfluenza virus; phase III trial; preclinical study; protein complex; remdesivir; research clinical testing; resistance mechanism; resistance mutation; variant detection; variants of concern; viral genomics; virology; whole genome

Project Summary – Core D The ability of RNA viruses to rapidly mutate and develop resistance to medical countermeasures is a considerable barrier to the development of broadly acting antivirals. Viral genotyping can help determine the mechanistic basis and degree of barrier to the development of antiviral resistance. The Genomics Core will provide accurate, timely, and reproducible viral whole genome sequencing data for all Projects in the Antiviral Countermeasures Development Center (AC/DC). Dr. Alex Greninger, Core Leader, is Assistant Director at the UW Virology Lab and has over 15 years of experience in viral genomics and molecular testing. Using a combination of different sequencing approaches including metagenomic, hybridization capture, and amplicon tiling combined with a clinical trials-grade quality management infrastructure, our laboratory has built a robust and automated wet-lab and dry-lab pipeline for the recovery of RNA virus genomes. With the Center’s focus on developing and characterizing broadly acting RNA polymerase-directed antivirals against a variety of RNA viruses, the Genomics Core can simultaneously offer information on the mechanisms of resistance and activity of these antivirals using sequencing data as a readout. Specifically, we will recover viral whole genomes from viral isolates subjected to selection with the proposed antiviral compounds during in vitro and in vivo experiments to determine mechanisms of resistance and activity. In addition, the Genomics Core will enhance rigor, reproducibility, and generalizability of the proposed studies by ensuring the integrity of viral isolates and constructs prior to labor-intensive and expensive in vivo experimentation in all Projects. The Core ensures that the Research Projects can obtain accurate results from high-throughput genomics testing without redundant effort to enable scientific inquiry into the activity of antivirals against a variety of high consequence RNA viruses.

项目摘要-核心D RNA病毒快速变异并对医学对策产生抗性的能力是一种重要的生物学机制。 这对开发广泛作用的抗病毒药物是一个相当大的障碍。病毒基因分型可以帮助确定 抗病毒耐药性发展的机制基础和障碍程度。基因组学核心将 为所有抗病毒项目提供准确、及时和可重复的病毒全基因组测序数据 反制发展中心（AC/DC）。Alex Greninger博士，核心领导人，是助理主任， UW病毒学实验室，在病毒基因组学和分子检测方面拥有超过15年的经验。使用 不同测序方法的组合，包括宏基因组、杂交捕获和扩增子 瓷砖与临床试验级质量管理基础设施相结合，我们的实验室已经建立了一个强大的 以及用于回收RNA病毒基因组的自动化湿实验室和干实验室流水线。随着中心的重点放在 开发和表征针对各种RNA的广泛作用的RNA聚合酶导向的抗病毒药物 基因组学核心可以同时提供有关抗性和活性机制的信息 这些抗病毒药物的测序数据作为读数。具体地说，我们将恢复病毒的整个基因组， 在体外和体内实验期间用所提出的抗病毒化合物进行选择的病毒分离株 以确定耐药性和活性的机制。此外，基因组学核心将提高严谨性， 通过确保病毒分离株的完整性， 在所有项目中进行劳动密集型和昂贵的体内实验之前构建。核心确保 研究项目可以从高通量基因组学测试中获得准确的结果，而不会产生冗余 努力使科学调查的活性抗病毒药物对各种高后果的RNA病毒。