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Deciphering the Role of Gut Microbiome in Inflammatory Bowel Disease Using a Canine Patient-Specific Gut-on-a-Chip

使用犬类患者特异性肠道芯片解读肠道微生物组在炎症性肠病中的作用

基本信息

批准号：
10369046
负责人：
Yoko Miyamoto Ambrosini
金额：
$ 10.26万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10369046
关键词：
16S ribosomal RNA sequencing Advanced Development Affect Alzheimer&apos s Disease Animal Model Anti-Inflammatory Agents Attention Bioinformatics Canis familiaris Cell Culture Techniques Cells Chronic Coculture Techniques Colorectal Cancer Complex Development Development Plans Diabetes Mellitus Disease Disease model Electron Microscopy Enrollment Epidemiology Epithelial Experimental Models Extramural Activities Functional disorder Funding Gastroenterology Genetic Genetic Heterogeneity Genetic Variation Genome Genomics Germ-Free Goals Health Heterogeneity Homeostasis Human Image Immune Impairment In Situ In Situ Hybridization In Vitro Individual Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Intestines Knowledge Lead Learning Libraries Maps Medicine Mentored Research Scientist Development Award Mentors Microfabrication Microfluidic Microchips Microfluidics Mission Modeling Molecular Biology Molecular Genetics Molecular Profiling Mutation Names Organoids Outcome Pathogenesis Pathologic Patients Persons Pharmaceutical Preparations Physiological Physiology Protocols documentation RNA RNA Sequences Research Research Personnel Role Scanning Scientist Techniques Technology Therapeutic Therapeutic Intervention Training Transmission Electron Microscopy United States National Institutes of Health Validation Visualization Work base canine model career development cell type cohort combinatorial comparative design dysbiosis gut microbiome gut microbiota host microbiome human disease human model improved in vitro Model insight intestinal epithelium intestinal homeostasis microbial microbial signature microbiome microbiome research multiple omics new therapeutic target novel novel therapeutics organ on a chip patient oriented pre-clinical programs research and development response single-cell RNA sequencing skills spatiotemporal stem cell biology stem cells tenure track transcriptome transcriptomics translational medicine

项目摘要

PROJECT SUMMARY This NIH ORIP K01 award application describes a 5-year training plan designed to allow me to gain additional skill and knowledge so that I can transition to an independent R01-funded tenure track research scientist. In carrying out the proposed research and career development plan, I will add to my scientific repertoire and acquire expertise in intestinal stem cell biology, microbiome, and microfluidic organ-on-chip technology. Using this newly acquired expertise, I will establish a scientific niche that will set me apart from my mentors and pave the way to a robust, extramurally funded research program. With the support of my mentoring team, I have designed a robust research program that leverages my extensive expertise with comparative gastroenterology and molecular biology. Specifically, Aim 1 will demonstrate molecular and genetic alterations affecting canine IBD following the development and validation of a patient-specific IBD model that can quantitatively assess the cellular and molecular signature of host-microbiome crosstalk. Aim 2. will allow mapping of the microbial signature and epithelial integrity in response to the host-microbiome intercellular crosstalk by utilizing single-cell level multi-omics (especially genomics and transcriptomics) and RNA in situ hybridization. Consistent with the ORIP’s mission statements promoting veterinary scientists to employ their expertise in comparative medicine to investigate human diseases, my research will allow me to use my expertise in comparative gastroenterology as well as in primary stem cell culture to investigate alterations in intestinal homeostasis relevant to Inflammatory Bowel Disease. Also, as ORIP supports animal modeling of human diseases, I will be using the dog as a spontaneous animal model to investigate the effect of gut microbiota in the intestinal epithelium given their genetic and physiological similarity to humans. The results generated in this proposal have direct implications for human diseases, since they will provide new insights into genetic and transcriptomic alterations initiating or maintaining the chronic inflammation in the gut. Such findings can be applied to various chronic conditions that have been epidemiologically associated with microbiome dysbiosis and disturbances of intestinal health (i.e., Colorectal Cancer, Diabetes Mellitus, and Alzheimer’s Disease, to name a few). This knowledge may be applied to understand disease development and novel therapies aimed at modifying intestinal homeostasis via perturbation of epithelium-microbiome-immune axis in the intestine. In summary, the training goals and career development activities proposed in this application will promote my successful transition into independent research directions.

项目总结