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Engineering Novel Enteroid Models for Understanding Human Enteric Disease

工程新肠模型用于了解人类肠道疾病

基本信息

批准号：
9234469
负责人：
Mary Kolb Estes
金额：
$ 103.37万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-15 至 2020-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9234469
关键词：
3-Dimensional Acute Address Administrator Animal Model Award Bacteria Bacteriology Basic Science Biocompatible Materials Biological Models Biomedical Engineering Biopsy Cancer Center Cells Cessation of life Chronic Clinical Clinical Microbiology Collaborations Communicable Diseases Communities Complement Complex Core Facility Dehydration Development Developmental Biology Diarrhea Diarrheagenic E. coli Disease Engineering Enteral Epithelial Epithelial Cells Feedback Food Contamination Functional disorder Funding Genetic Genetic Predisposition to Disease Genomics Goals Human Immune In Vitro Individual Infection Infectious Disease Epidemiology Infectious Diseases Research Ingestion Institution Intestinal Diseases Intestines Kidney Knowledge Lead Life Mechanics Medical center Medicine Mesenchymal Microbe Modeling Molecular Organism Outcome Pathogenesis Pathogenicity Pathology Pathway interactions Physicians Physiological Physiology Pilot Projects Population Heterogeneity Predisposition Printing Probiotics Productivity Property Reproducibility Request for Applications Research Research Personnel Research Project Grants Resources Rice Rotavirus Rotavirus Vaccines Scientist Senior Scientist Services Stretching Symbiosis System Testing Texas Tissue Engineering Tissues Translational Research Universities Vascularization Villus Virus Vomiting Work biomaterial development cell type college contaminated water cost design expectation experience genetic manipulation human disease improved in vivo Model innovation meetings microbial microbiome microbiota microorganism multidisciplinary new technology novel novel strategies pathogen pathogenic bacteria preclinical study prevent programs public health relevance response success synergism technology development tissue tropism virology work-study

项目摘要

DESCRIPTION OF THE OVERALL U19 APPLICATION (provided by applicant): This application requests funding of a NAMSED Cooperative Research Center (called CRC for simplicity) in the Texas Medical Center. This CRC's primary objective will be achieved through the collaborative efforts of a multidisciplinary, integrated team of basic scientists, biomedical engineers and a physician scientist who are at three institutions (Baylor College of Medicine (BCM), Rice University, the MD Anderson Cancer Center). The overall goal of this CRC is to create the first ex-vivo mini-gut model systems that are physiologically active and mimic many aspects of human intestine. We will use human intestinal enteroids (HIEs) derived from human intestinal biopsies to address key questions about human enteric disease caused by microorganisms that produce human diarrheal disease and lead to ~4% of all deaths worldwide. New models that adequately reflect relevant human physiology, pathophysiology and natural host-pathogen interactions are critically needed because most human pathogens that cause diarrheal disease lack animal models that accurately mimic the human disease. This CRC application integrates a team with multidisciplinary expertise including basic and translational research and innovation in virology, bacteriology including the microbiome, genomics, developmental biology and physiology, biomedical engineering and biomaterial development of engineered tissues including in vitro vascularization and 3D printing, infectious disease epidemiology and clinical microbiology. This CBC will consist of 3 Projects and 3 Core facilities. Project 1 will use HIEs to analyze genetically-regulated host restriction to human rotavirus and vaccine replication and to define epithelial cell responses that lead to pathophysiology. Project 2 will use HIEs to understand the pathogenesis of infections with diarrheagenic E. coli including factors that characterize differences between acute and chronic infections, tissue tropism and mechanisms of pathology. Project 3 will combine tissue engineering, biomaterial design, and mechanobiology to develop tailored, biofunctional platforms for HIEs that can be mechanically stimulated and that will promote cell and tissue polarity as well as the full crypt-villus differentiation to facilitate infection with commensals and enteropathogens. These 3 interrelated and synergistic projects will be supported by the specialized and intellectual contributions of 3 Core Facilities: the Administrative Core, Human Enteroid Core, and Genomics and Microbiome Core. Two Pilot Developmental Research Projects will be supported with one being funded by BCM. The success of this CRC depends on the complementary expertise of the individual investigators and center leaders who are senior scientists-administrators experienced in directing interactive, multidisciplinary programs. Collaboration and iterative feedback between biomedical engineers, local biologists and other NAMSED investigators will facilitate progress towards developing an ideal system that will be state of the art yet sufficiently simple for routin use in infectious disease laboratories and adequately robust for use in pre-clinical studies.