Core C: Proteogenomics Core

核心 C：蛋白质组学核心

• 批准号: 10394317
• 负责人: Andrew Laurence Routh
• 金额: $ 36.12万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394317
• 关键词: ATAC-seq; Acetylation; Address; Alternative Splicing; Antibodies; Antigen-Antibody Complex; Bioinformatics; Cell Culture Techniques; Cells; ChIP-seq; Chromatin; Chromium; Collaborations; Column Chromatography; Complex; Computer Analysis; DNA; DNA Methylation; Data; Data Analyses; Data Files; Databases; Dendritic Cells; Deposition; Disabled Persons; Ebola virus; Epigenetic Process; Event; Evolution; Experimental Designs; Filovirus; Flavivirus Infections; Fractionation; Gene Expression; Genetic Transcription; Goals; Histone Acetylation; Human; Immune; Immune response; Infection; Infrastructure; Interferons; Libraries; Mass Spectrum Analysis; Massive Parallel Sequencing; Medical; Messenger RNA; Methodology; Modeling; Modification; Molecular; Molecular Biology; Molecular Conformation; Monitor; Output; Pathology; Phosphorylation; Poly A; Polyadenylation; Population; Post-Translational Protein Processing; Procedures; Protein Analysis; Protein Isoforms; Proteins; Proteome; Proteomics; Publications; Quality Control; RNA; RNA Viruses; RNA chemical synthesis; RNA metabolism; Reaction; Records; Research; Research Project Grants; Research Support; Resolution; Role; Sampling; Schedule; Signal Transduction; Technology; Texas; Tissue-Specific Gene Expression; Transcript; Translations; Ubiquitin; Ubiquitination; Universities; Viral; Virus Diseases; base; bisulfite sequencing; cell type; conformational alteration; dynamic system; experience; experimental study; frontier; high throughput technology; histone methylation; innovation; instrument; member; mutant; nanopore; next generation sequencing; nonhuman primate; novel; novel sequencing technology; phenome; protein expression; proteogenomics; public database; response; ribosome profiling; single-cell RNA sequencing; transcriptome; transcriptome sequencing; transcriptomics

PROTEOGENOMICS CORE (Core C): PROJECT SUMMARY/ABSTRACT Ebola virus (EBOV) and other filoviruses cause devastating pathology, resulting in large part from a dysregulated immune response. At present, our characterization of immune cell-specific responses to EBOV is limited. To address this complex issue, the research projects of this proposal will employ a wide range of OMICS and high- throughput technologies focused at each stage of the “central dogma”; from RNA synthesis, through RNA metabolism, to protein translation and modification. The role of the Proteogenomics Core (Core C) will be to apply cutting-edge massively parallel sequencing and proteomics approaches in support of Research Projects 1, 2, and 3, and to develop novel procedures and technologies to tackle the uniquely complex immune response to EBOV. We will use a combination of short-read (Illumina) and long-read (Nanopore) approaches to characterize epigenetic, transcriptional, and posttranscriptional responses to EBOV infection. Output from sequencing and proteomic analysis will be integrated with the Bioinformatics and Modeling Core (Core D) and deposited in public databases. Finally, these results will be interpreted together with the original main Projects. The Proteogenomics Core comprises a group of experts with experience in the implementation of the wide range of approaches in molecular biology, experimental design, and downstream computational analyses. Core C has a well established track record of innovating novel and cutting-edge methodologies in both next-generation sequencing and mass spectrometry, and can therefore develop and provide state-of-the-art technical support to advance the proposed research to new frontiers. The core will be directed by Dr. Routh, an expert in applying novel sequencing technologies to study RNA virus evolution, transcriptomics, and bioinformatics. Drs. Russell and Widen (Associate Core Leads) are directors of the mass spectrometry and next-generation sequencing facilities, respectively, at the University of Texas Medical Branch. The overarching goal of the Proteogenomics Core is to provide a comprehensive and unprecedented characterization of the “phenome” of cells infected by EBOV, both in cell culture and NHP models. By comparing changes in the epigenetic landscape to observed perturbations in the transcriptome, we will first determine how these events are coordinated and subsequently manifest as changes in the host proteome.

蛋白基因组学核心（核心C）：项目总结/摘要 埃博拉病毒（EBOV）和其他丝状病毒引起毁灭性的病理学，这在很大程度上是由于病毒引起的免疫调节失调。 免疫反应目前，我们对EBOV的免疫细胞特异性应答的表征是有限的。到 为了解决这个复杂的问题，本提案的研究项目将采用广泛的OMICS和高- 通量技术集中在“中心法则”的每个阶段;从RNA合成，通过RNA 代谢，蛋白质翻译和修饰。蛋白质基因组学核心（Core C）的作用是： 应用尖端的大规模并行测序和蛋白质组学方法来支持研究项目 1，2和3，并开发新的程序和技术，以解决独特的复杂免疫反应 关于EBOV我们将使用短读（Illumina）和长读（Nanopore）方法的组合， 表征对EBOV感染的表观遗传、转录和转录后应答。输出 测序和蛋白质组学分析将与生物信息学和建模核心（核心D）集成 并存入公共数据库。最后，这些结果将与原始的主要结果一起解释。 项目 蛋白基因组学核心由一组在实施广泛的 分子生物学、实验设计和下游计算分析的一系列方法。核心 C在下一代和新技术领域创新新颖和尖端的方法方面有着良好的记录， 测序和质谱，因此可以开发和提供最先进的技术支持， 将拟议的研究推进到新的领域。核心将由应用专家劳斯博士指导 新的测序技术，研究RNA病毒进化，转录组学和生物信息学。罗素博士 和Widen（副核心领导）是质谱和下一代测序的主管 设施，分别在得克萨斯大学医学分支。 蛋白质基因组学核心的总体目标是提供一个全面的和前所未有的 在细胞培养物和NHP模型中，EBOV感染的细胞的“表型组”的表征。通过比较 在表观遗传景观的变化，观察到的干扰转录组，我们将首先确定如何 这些事件是协调的，随后表现为宿主蛋白质组的变化。