Model-guided design of next-generation bacterial therapeutics to treat cardiovascular disease

模型引导设计下一代治疗心血管疾病的细菌疗法

基本信息

批准号：
10249177
负责人：
Federico E Rey
金额：
$ 66.72万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10249177
关键词：
Address Bacteriophages Bacteroides Behavior Biosensor Butyrates Cardiovascular Diseases Cause of Death Communities Complex Computer Models Data Development Disease Ecosystem Engineering Equilibrium Escherichia coli Feedback Gastrointestinal tract structure Genetic Transcription Germ-Free Gnotobiotic Goals Health Human In Vitro Intervention Intestines Lead Machine Learning Mediating Medicine Methodology Methods Modeling Organism Performance Phenotype Physiology Probiotics Process Production Protein Engineering Proteins Scientist Stimulus Structure System Techniques Therapeutic Time Work antimicrobial computer framework design dynamic system gut microbiome gut microbiota human disease lysin member microbial microbial community microbiome microbiome alteration mouse model next generation novel novel therapeutic intervention personalized medicine predictive modeling prototype real time monitoring response sensor therapy design tool trimethylamine

项目摘要

PROJECT SUMMARY/ABSTRACT It is becoming increasingly evident that the composition and metabolites produced by the human gut microbiome influence the progression of cardiovascular diseases. While we are continuing to discover important associations between the gut microbiome and human physiology and diseases, we lack the tools and methodology to precisely manipulate gut microbiota to benefit human health. We propose to develop computational models and optimization frameworks to predict community dynamics and functions and design interventions to shift the gut microbiome to desired states. We will design novel bacterial therapeutics that operate autonomously in the mammalian gastrointestinal tract to steer the microbiome towards healthy states. These next-generation bacterial therapeutics will sense important gut microbiome metabolites, process information, and deliver species- specific antimicrobial proteins to reshape the dynamics and functions of this ecosystem. The performance of these bacterial therapeutics will be characterized in vitro using synthetic human gut microbiome communities and in gnotobiotic mouse models of cardiovascular disease. Model-guided microbiome engineering has the potential to transform human medicine and is becoming increasingly important as scientists continue to discover connections between the microbiome and human health and disease.

项目摘要/摘要越来越明显的是，人类肠道微生物组产生的成分和代谢产物影响心血管疾病的进展。在我们继续发现重要协会的同时在肠道微生物组和人类生理学和疾病之间，我们缺乏工具和方法论精确操纵肠道菌群以使人类健康受益。我们建议开发计算模型和优化框架预测社区动态，功能和设计干预措施以改变肠道微生物组到所需状态。我们将设计新颖的细菌疗法，以在哺乳动物胃肠道将微生物组引导到健康状态。这些下一代细菌疗法将感觉到重要的肠道微生物组代谢物，过程信息并传递物种 - 特定的抗微生物蛋白可以重塑该生态系统的动力学和功能。性能这些细菌疗法将在体外使用合成人肠道微生物组社区进行体外表征在心血管疾病的gnotobiotic小鼠模型中。模型引导的微生物组工程具有随着科学家的继续发现，改变人类医学并变得越来越重要微生物组与人类健康与疾病之间的联系。