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：
10044931
负责人：
Federico E Rey
金额：
$ 69.75万
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/10044931
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 novel therapeutics 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.

项目概要/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物影响心血管疾病的进展。当我们不断发现重要的关联时在肠道微生物群与人类生理和疾病之间，我们缺乏工具和方法来精准调控肠道菌群，造福人类健康。我们建议开发计算模型和预测群落动态和功能的优化框架，并设计干预措施来改变肠道微生物组达到所需状态。我们将设计能够在环境中自主运行的新型细菌疗法哺乳动物胃肠道引导微生物组走向健康状态。这些下一代细菌疗法将感知重要的肠道微生物代谢物、处理信息并传递物种—— 特定的抗菌蛋白重塑该生态系统的动态和功能。性能这些细菌疗法将使用合成的人类肠道微生物群落在体外进行表征以及心血管疾病的无菌小鼠模型。模型引导的微生物组工程具有随着科学家不断发现，它具有改变人类医学的潜力，并且变得越来越重要微生物组与人类健康和疾病之间的联系。