High Resolution Characterization of Bacterial Epigenomes and Microbiome

细菌表观基因组和微生物组的高分辨率表征

• 批准号: 10385975
• 负责人: Gang Fang
• 金额: $ 5.26万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10385975
• 关键词: Adenine; Antibiotic Resistance; Bacteria; Bacterial DNA; Basic Science; Biological; Bypass; Cell Cycle Regulation; Communicable Diseases; Communities; Cytosine; DNA Methylation; DNA Restriction-Modification Enzymes; Defense Mechanisms; Development; Drug resistance; Environment; Epigenetic Process; Event; Gene Expression; Genome; Goals; Heterogeneity; Immune system; Individual; Invaded; Maps; Metabolism; Methods; Methylation; Microbial Biofilms; Microbiology; Nucleotides; Organism; Play; Research; Resolution; Role; Techniques; Virulence; cdc Genes; commensal bacteria; epigenetic regulation; epigenome; gut microbiome; host-microbe interactions; innovation; insight; methylome; microbiome; new technology; novel; pathogen; programs; public health relevance; response; single molecule real time sequencing; software development; symposium; technology development

PROJECT SUMMARY/ABSTRACT My long term goal is to comprehensively understand the diversity, heterogeneity and functions of bacterial epigenomes both in terms of basic science and biomedical impact. In the bacterial world, methylated adenine and cytosine residues was previously thought to be only associated with restriction-modification systems that provide a defense mechanism against invading foreign genomes. However, increasing evidence supports that they also play important roles in the regulation of cell cycle, gene expression, virulence, sporulation, biofilm formation, microbe-host interaction and antibiotic resistance. Efficient and high resolution profiling of bacterial DNA methylation events has not been possible until the advent of Single Molecule Real-Time (SMRT) sequencing. This technique enabled us to characterize the first bacterial methylome at single nucleotide resolution. A fast growing number of bacteria are being characterized, from which exciting discoveries have been made. However, these studies have also revealed unexpected complexity and diversity in bacterial methylomes, calling for the development new technologies, analytical and experimental methods in order to more comprehensively understand bacterial epigenomes. In this R35 project, we will build on the progress we have made in the past five years to further develop an integrated research program with a broader scope integrating two ongoing focused R01 projects. The overarching theme is focused on the mapping, characterization and exploitation of bacterial methylomes to better understand individual bacteria and microbiome community. We will develop this research program along four complementary themes. First, to more comprehensively map bacterial methylome, we will continue to innovate on technology development to make significant improvements both in terms of in terms of completeness and resolution. Second, to better elucidate epigenetic regulation in bacteria, we will combine computational and experimental approaches to prioritize and functionally characterize specific methylation events across different bacterial organisms. Third, to systematically expand bacterial methylome research from cultured individual bacteria to microbiome, we will characterize bacterial epigenetics in response to different types of perturbations. Last, we will provide the software we develop as an integrated package to ease broad usage, and organize relevant conference tutorials to help the broader community. Combined together, we expect this project to provide broadly applicable methods to the microbiology and microbiome community, and discover novel biological insights into epigenetic regulation in individual bacteria and microbiome.

项目摘要/摘要 我的长期目标是全面了解细菌的多样性，异质性和功能 在基础科学和生物医学影响方面的表观基因组。在细菌世界中，甲基化的腺嘌呤 胞嘧啶残基以前被认为仅与限制性修饰系统有关 提供防御机制，以防止入侵外国基因组。但是，越来越多的证据支持 它们还在细胞周期，基因表达，毒力，孢子形成，生物膜的调节中起重要作用 形成，微生物宿主相互作用和抗生素耐药性。细菌的有效且高分辨率分析 直到单分子实时出现（SMRT），DNA甲基化事件是不可能的 测序。该技术使我们能够表征单个核苷酸的第一个细菌甲基 解决。快速增长的细菌正在表征，令人兴奋的发现有 被制作了。但是，这些研究还揭示了细菌的意外复杂性和多样性 甲基瘤呼吁开发新技术，分析和实验方法，以便 更全面地了解细菌表观基因质。在这个R35项目中，我们将基于我们的进步 在过去的五年中，已经建立了更广泛的范围的综合研究计划 集成了两个正在进行的重点R01项目。总体主题集中于映射， 对细菌甲基组的表征和剥削，以更好地了解单个细菌和 微生物组社区。我们将以四个互补主题制定该研究计划。首先，到 更全面地绘制细菌甲基组，我们将继续对技术开发进行创新 就完整性和解决方案而言，取得重大改进。第二，更好 阐明细菌中的表观遗传调节，我们将结合计算和实验方法 优先和功能表征不同细菌生物的特定甲基化事件。第三， 为了系统地将细菌甲基甲基组的研究从培养的个体细菌到微生物组，我们将 表征细菌表观遗传学，以响应不同类型的扰动。最后，我们将提供 我们开发的软件作为集成软件包，以简化广泛的用法，并组织相关会议 教程可帮助更广泛的社区。结合在一起，我们希望该项目能够广泛地提供 适用于微生物学和微生物组社区的方法，并发现新颖的生物学见解 单个细菌和微生物组的表观遗传调节。