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.

蛋白质组学核心(核心C)：项目摘要/摘要 埃博拉病毒(EBOV)和其他丝状病毒会造成毁灭性的病理，导致很大程度上是由于 免疫反应。目前，我们对EBOV免疫细胞特异性反应的描述有限。至 为了解决这个复杂的问题，这项建议的研究项目将使用广泛的OMICS和高 从RNA合成到RNA，集中在“中心法则”的每个阶段的吞吐量技术 代谢，到蛋白质的翻译和修饰。蛋白质组学核心(核心C)的作用将是 应用尖端大规模并行测序和蛋白质组学方法支持研究项目 1、2和3，并开发新的程序和技术来应对独特的复杂免疫反应 致EBOV。我们将结合使用短读(Illumina)和长读(Nanopore)方法来 表征表观遗传、转录和转录后对EBOV感染的反应。输出自 测序和蛋白质组分析将与生物信息学和建模核心(核心D)整合 并存入公共数据库。最后，这些结果将与原始的主要内容一起进行解释 项目。 蛋白质组学核心由一组在实施Wide的经验的专家组成 分子生物学、实验设计和下游计算分析的一系列方法。堆芯 C在创新新一代和尖端方法方面有着良好的记录 测序和质谱学，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 研究RNA病毒进化、转录组和生物信息学的新测序技术。罗素博士 和威登(联席核心领导)是质谱学和下一代测序的负责人 分别位于德克萨斯大学医学部的设施中。 蛋白质组学核心的首要目标是提供全面和前所未有的 在细胞培养和NHP模型中，EBOV感染细胞的“表现组”的特征。通过比较 表观遗传格局的变化对转录组中观察到的扰动，我们将首先确定如何 这些事件是相互协调的，随后表现为宿主蛋白质组的变化。