Core D - Genomics

核心 D - 基因组学

基本信息

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
项目类别：
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

项目摘要

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病毒快速突变和发展对医学对策的能力是开发广泛作用抗病毒药的障碍。病毒基因分型可以帮助确定抗病毒耐药性发展的机械基础和障碍程度。基因组核心将为抗病毒中的所有项目提供准确，及时和可重现的病毒全基因组测序数据对策开发中心（AC/DC）。核心负责人Alex Greninger博士是 UW病毒学实验室，在病毒基因组学和分子测试方面拥有超过15年的经验。使用包括宏基因组，杂交捕获和放大器在内的不同测序方法的组合瓷砖与临床试验级质量管理基础设施相结合，我们的实验室建立了强大的以及自动湿LAB和干lab管道，用于恢复RNA病毒基因组。中心的重点开发和表征广泛作用的RNA聚合酶指导的抗病毒药物针对各种RNA 病毒，基因组学核心可以轻松地提供有关抗药性和活动机制的信息这些抗病毒药使用测序数据作为读数。具体而言，我们将从在体外和体内实验期间选择接受建议的抗病毒化合物的病毒分离株确定电阻和活性的机制。此外，基因组学核心将增强严格性，通过确保病毒分离株的完整性和在所有项目中进行劳动密集型和昂贵的体内实验之前的构造。核心确保研究项目可以从高通量基因组测试中获得准确的结果，而无需多余努力使科学探究抗病人对各种高结果RNA病毒的活性。