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Integrated Genomics of Mucosal Infections

粘膜感染的综合基因组学

基本信息

批准号：
10160776
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
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10160776
关键词：
Achievement Address Adoption Allergic Asthma Bacteriology Basic Science Biological Models Biomedical Engineering Cancer Center Clinical Clinical Microbiology Cloud Computing Collection Communicable Diseases Communities Cryptosporidiosis Cryptosporidium Custom Detection Development Developmental Biology Diagnostic Digestive System Disorders Disease Doctor of Philosophy Drug resistance Elements Enterobacteriaceae Enterococcus faecalis Enterococcus faecium Epithelial Escherichia coli Evolution Feces Foundations Funding 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 Inflammation 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 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 base clinical practice clinically relevant college commensal bacteria commensal microbes data management data tools 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 transcriptomics vaccine development virology virome

项目摘要

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.

整体项目总结