Collaborative Research: Model-guided design of bacterial interspecies interactions and trans-organismic communication in living intercellular circuits

合作研究：活体细胞间回路中细菌种间相互作用和跨有机体通讯的模型引导设计

基本信息

批准号：
2211039
负责人：
Lauren Andrews
金额：
$ 66.89万
依托单位：
University of Massachusetts Amherst
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-15 至 2025-04-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2211039&HistoricalAwards=false
关键词：
Collaborative Research Model guided design

项目摘要

Bacteria in the environment live in multispecies communities with dynamic interactions that can bring about complex collective behaviors. Bacteria use biochemical cell-to-cell communication via diffusible molecules and gene regulatory elements to bring about large-scale responses. The ability to predictably design multicellular responses in diverse bacterial communities would have a wide range of applications including efficient biomanufacturing, bioenergy conversion, novel therapeutic strategies, sustainable agriculture, and bioremediation. To date, numerous naturally occurring interactions and modes of communication within bacterial communities have been identified, yet there is not the ability to engineer synthetic bacterial communities that have these complex interactions and dynamic responses among diverse bacteria. This collaborative project aims to improve understanding of interspecies biochemical cell-cell communication that can occur in natural microbial communities and allow us to leverage the highly complex functions afforded by these systems within synthetic diverse bacterial communities as programmable living devices. This project will create synthetic bacterial consortia for biosensing and bioremediation of many hazardous water contaminants, including some of the most dangerous drinking water and aquatic ecosystem contaminants. This project will provide education and research training for numerous K-12, undergraduate, and graduate students. Hands-on workshops will be run at UMass Amherst and Boston University each year for high school students to learn about studying and engineering bacterial communities. Many undergraduate opportunities for synthetic biology research training will be created. These educational activities will increase K-12 STEM education, help address the underrepresentation of women and minorities in synthetic biology, and train the next generation of scientists and engineers. The goal of this project is to establish a generalizable framework for the design of multicellular transcriptional regulatory networks distributed within bacterial communities containing gram-negative and gram-positive bacteria. The universality of recent discoveries of homoserine lactone-mediated quorum sensing in gram-positive bacteria will be determined using libraries of LuxRI-type quorum sensing systems and model gram-positive bacteria. This work will generate a set of standardized quorum sensors for gram-positive bacteria that allow for controlling interspecies communication between diverse bacteria. The sequence-function relationship for these quorum sensing systems will be determined using statistical design and systematic mutagenesis. Using these quorum sensors, the team will test fundamental questions about the evolution of quorum sensing in bacteria. A high-throughput multilayer microfluidics platform for studying and maintaining bacterial communities will be developed to analyze temporal signaling at single-cell resolution. This platform will be used to develop a database of parameters and models to predict the signaling dynamics of these distributed transcriptional regulatory networks. This work aims to enable researchers to create diverse bacterial communities that have complex interactions, designable interspecies communication, and prescribed dynamic responses.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

环境中的细菌生活在具有动态相互作用的多种社区中，可以带来复杂的集体行为。细菌通过可扩散分子和基因调节元件使用生化细胞对细胞通信来产生大规模反应。可以预测的在不同细菌群落中设计多细胞反应的能力将具有广泛的应用，包括有效的生物制造，生物能量转化，新型治疗策略，可持续的农业和生物修复。迄今为止，已经确定了细菌群落中许多自然发生的相互作用和交流方式，但是没有能力来设计具有这些复杂相互作用和动态反应的各种细菌中的合成细菌群落。该协作项目旨在提高对天然微生物社区可能发生的种间生物化学细胞 - 细胞传播的理解，并使我们能够利用这些系统在合成的各种细菌群落中提供的高度复杂功能作为可编程的生活设备。该项目将创建合成细菌联盟，用于对许多有害水污染物的生物传感和生物修复，包括一些最危险的饮用水和水生生态系统污染物。该项目将为许多K-12，本科生和研究生提供教育和研究培训。动手讲习班每年都会在UMass Amherst和波士顿大学举行，以便高中生学习学习和工程细菌社区。将创造许多合成生物学研究培训的本科生。这些教育活动将增加K-12的STEM教育，有助于解决合成生物学中妇女和少数民族的代表性不足，并培训下一代科学家和工程师。该项目的目的是建立一个可推广的框架，用于设计分布在包含革兰氏阴性和革兰氏阴性细菌的细菌群落中的多细胞转录调节网络。革兰氏阳性细菌中同碱内酯介导的群体传感的最新发现的普遍性将使用Luxri-Type Quorum Sensing Systems和模型革兰氏阳性细菌的库来确定。这项工作将为革兰氏阳性细菌生成一组标准化的法定人数传感器，以控制各种细菌之间的种间通信。这些法定感应系统的序列功能关系将使用统计设计和系统诱变确定。使用这些法定人数传感器，团队将测试有关细菌中法定感测的演变的基本问题。将开发用于研究和维持细菌群落的高通量多层微流体平台，以分析单细胞分辨率的时间信号。该平台将用于开发参数和模型数据库，以预测这些分布式转录调节网络的信号传导动力学。这项工作旨在使研究人员能够创建具有复杂互动，可设计的种间交流和规定动态反应的各种细菌群落。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准通过评估来获得支持的。