Integrated Genomics of Mucosal Infections

粘膜感染的综合基因组学

• 批准号: 10601123
• 负责人: RICHARD A GIBBS
• 金额: $ 390万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601123
• 关键词: Acceleration; Achievement; Address; Adoption; Allergic; Asthma; Bacteriology; Basic Science; Biological Models; Biomedical Engineering; Cancer Center; Clinical; Clinical Microbiology; Cloud Computing; Collection; Commercial grade; Communicable Diseases; Communities; Cryptosporidiosis; Cryptosporidium; Data; Detection; Development; Developmental Biology; Diagnostic; Digestive System Disorders; Disease; Doctor of Philosophy; Drug resistance; Elements; Enterobacteriaceae; Enterococcus faecalis; Enterococcus faecium; Epithelium; Escherichia coli; Evolution; Feces; Funding; Gastrointestinal Diseases; Gene Expression Profile; Generations; Genetic Recombination; Genomic Centers for Infectious Diseases; Genomics; Goals; Health; High-Throughput Nucleotide Sequencing; Human; Immune response; Individual; Indoles; Infection; Infectious Diseases Research; Innate Immune Response; Institution; Integration Host Factors; Intestinal Diseases; Intestinal Mucosa; Intestines; Klebsiella pneumoniae; Length; Lung; Lung diseases; Medical center; Medicine; Metagenomics; Microbe; Modeling; Mucous Membrane; Multi-Drug Resistance; Norovirus; Organoids; Parasites; Parasitology; Pathogenesis; Pathogenicity; Phenotype; Physicians; Physiological; Physiology; Pilot Projects; Predisposition; Probiotics; Process; Public Health Schools; Pulmonary Inflammation; Reagent; Request for Applications; Research Project Grants; Resistance; Resources; Respiratory System; Respiratory syncytial virus; Role; Sampling; Scientist; Specialist; System; Technology; Testing; Texas; Therapeutic; Time; Translational Research; United States National Institutes of Health; Universities; Vaccines; Viral; Virulence; Virulence Factors; Virus Diseases; Virus Replication; bacteriome; clinical practice; clinically relevant; college; commensal bacteria; commensal microbes; data management; drug development; experience; fungus; genetic profiling; genetic variant; genomic data; genomic variation; host-microbe interactions; human genome sequencing; human model; human tissue; infectious disease treatment; insight; large datasets; meetings; member; metagenomic sequencing; microbial; microbial community; microbial genomics; mouse model; multidisciplinary; novel; novel diagnostics; novel therapeutics; pathogen; patient subsets; precision medicine; prevent; pulmonary function; response; therapeutic development; tool; transcriptomics; vaccine development; virology; virome

Overall Project Summary This application requests funding for a Genomics Center for Infectious Disease (GCID) in the Texas Medical Center (TMC) that comprises a multidisciplinary, integrated team of basic and physician scientists at Baylor College of Medicine, the University of Texas-Houston School of Public Health, and MD Anderson Cancer Center. The overall goal of our GCID is to: i) leverage our decades of experience in genomic sequencing technology with our renowned clinical expertise, and the use of novel ex vivo organotypic models of human intestinal and pulmonary function, to create a platform for large scale genomics-based interrogation of host-mucosal pathogen interactions in the context of human tissues, and ii) utilize this platform for the discovery of novel therapeutic and diagnostic targets based on host and microbial genomic and transcriptomic profiles. Project 1 (PL: A. Maresso, PhD) will dissect the genomic elements that confer the ability of pathogenic members of the Enterobacteriaceae and Enterococcaceae to associate with the human intestinal mucosa while also determining the host response to this association. Project 2 (PL: M. Estes, PhD) will leverage integrated analyses of human norovirus and respiratory syncytial virus full-length genomic sequences and characterization of the ecological niche of samples from clinically relevant patient sub-groups for new understanding of viral replication, recombination and evolution, induction of disease and host factors required for susceptibility to infection and pathogenesis. Project 3 (PL: D. Corry, MD) will test the hypothesis that fungal diversity, virulence, and individual innate immune responses to fungal burdens underlie persistent, treatment-resistant moderate to severe asthma in a new paradigm whereby fungal burden within the respiratory tract (“airway mycosis”) may have a causative role in development and persistence of allergic lung inflammation. Project 4 (PL: P. Okhuysen, MD) will build on a novel Cryptosporidium discovery made by the project leaders and test the hypothesis that one or more indole-producing commensal microbes in the gut can prevent or eliminate Cryptosporidium infection. All four research projects will utilize human intestinal and lung organoid cultures along with niche-specific, defined microbial communities supplied by the Organoid and Minibioreactor Array Cultivation Core and a large collection of unique clinical samples and isolates, incorporating cutting edge, high-throughput sequencing strategies and technologies supplied by the Sequencing Technology (ST) Core. Paradigm-shifting discoveries, data, tools, and reagents will be disseminated to the infectious disease community by the Data Management Analysis and Resource Dissemination (DMARD) Core through a state of the art portal developed by DNAnexus. The result will be a comprehensive genetic profiling of hosts and microbes in human infection models that will reveal pathogen genetic variants, and individual host response phenotypes to inform precision medicine-based therapeutics and diagnostics, both for the pathogens in this proposal and a broad spectrum of mucosal infectious diseases that severely impact human health.

总体项目摘要 该申请要求为德克萨斯州医学的基因组传染病中心（GCID）提供资金 Center（TMC）包括贝勒（Baylor）的基本和物理科学家组成的多学科，综合团队 德克萨斯 - 霍斯顿大学公共卫生学院和医学博士安德森癌症中心医学院。 GCID的总体目标是：i）利用我们数十年的基因组测序经验 具有我们著名的临床专业知识的技术，以及新型的离体有机模型的使用 人类肠和肺功能，为大规模基因组学创建平台 在人体组织中对宿主粘膜病原体相互作用的询问，ii）利用这一点 基于宿主和微生物的新型热和诊断目标的发现平台 基因组和转录谱。项目1（PL：A。Maresso，博士）将剖析基因组元素 会议肠杆菌科和肠球科的病原体成员与 人类肠粘膜同时确定宿主对这种关联的反应。项目2（PL：M。Estes， 博士学位将利用人类诺如病毒和呼吸综合病毒全长基因组的综合分析 来自临床相关的患者子组样品的生态位序列和表征 对病毒复制，重组和进化，诱导疾病和宿主因素的新了解 需要感染和发病机理的易感性。项目3（PL：D。Corry，MD）将检验以下假设。 真菌多样性，病毒和个人对真菌伯伦斯持续存在的先天免疫调查， 在新的范式中，对治疗的现代化至严重哮喘，从而在呼吸道内燃烧。 区域（“气道霉菌病”）可能在过敏性肺部感染的发育和持久性中起因作用。 项目4（PL：MD P. Okhuysen）将建立在项目领导者的新颖隐孢子虫发现的基础上 并检验以下假设：肠道中的一个或多个产生的共生微生物可以预防或 消除隐孢子虫感染。所有四个研究项目都将利用人类肠道和肺器官 培养物以及小型和小型肌动物提供的小众特异性，定义的微生物群落 阵列培养核心以及大量独特的临床样品和分离株，编码尖端， 测序技术（ST）核心提供的高通量测序策略和技术。 范式转移发现，数据，工具和试剂将被传播到传染病社区 通过数据管理分析和资源传播（DMARD）核心通过最先进的门户网站 由Dnanexus开发。结果将是人类宿主和微生物的全面基因分析 感染模型将揭示病原体遗传变异和单个宿主反应表型通知 基于精密医学的治疗和诊断，既适用于该提案中的病原体，又是广泛的 严重影响人类健康的粘膜传染病范围。

项目成果

Mapping human norovirus antigens during infection reveals the breadth of the humoral immune response.

• DOI: 10.1038/s41541-023-00683-1
• 发表时间: 2023-06-06
• 期刊: NPJ vaccines
• 影响因子: 9.2

Fully resolved assembly of Cryptosporidium parvum.

• DOI: 10.1093/gigascience/giac010
• 发表时间: 2022-02-15
• 期刊: GigaScience
• 影响因子: 9.2
• 作者: Menon VK;Okhuysen PC;Chappell CL;Mahmoud M;Mahmoud M;Meng Q;Doddapaneni H;Vee V;Han Y;Salvi S;Bhamidipati S;Kottapalli K;Weissenberger G;Shen H;Ross MC;Hoffman KL;Cregeen SJ;Muzny DM;Metcalf GA;Gibbs RA;Petrosino JF;Sedlazeck FJ
• 通讯作者: Sedlazeck FJ

Inference of phylogenetic trees directly from raw sequencing reads using Read2Tree.

• DOI: 10.1038/s41587-023-01753-4
• 发表时间: 2024-01
• 期刊: NATURE BIOTECHNOLOGY
• 影响因子: 46.9
• 作者: Dylus, David;Altenhoff, Adrian;Majidian, Sina;Sedlazeck, Fritz J.;Dessimoz, Christophe
• 通讯作者: Dessimoz, Christophe

Comparative Pathogenomics of Escherichia coli: Polyvalent Vaccine Target Identification through Virulome Analysis.

• DOI: 10.1128/iai.00115-21
• 发表时间: 2021-07-15
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Clark JR;Maresso AM
• 通讯作者: Maresso AM

Functional Genomics of Gastrointestinal Escherichia coli Isolated from Patients with Cancer and Diarrhea.

从癌症和腹泻患者中分离出胃肠道大肠杆菌的功能基因组学。

• DOI: 10.1101/2023.05.31.543115
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Carter,Hannah;Clark,Justin;Carlin,LilyG;Vaughan,Ellen;Rajan,Anubama;Olvera,Adilene;Yu,Xiaomin;Zeng,Xi-Lei;Kambal,Amal;Holder,Michael;Qin,Xiang;Gibbs,RichardA;Petrosino,JosephF;Muzny,DonnaM;Doddapaneni,Harsha;Menon,Vipin
• 通讯作者: Menon,Vipin