CAREER: Engineering Interspecies Communication and Synthetic Microbial Consortia

具有工业重要性的化合物的生物合成通常需要对复杂的代谢途径进行工程和优化。传统上，这些工艺采用了重组微生物的克隆群体，如大肠杆菌或酵母。使用单一种群的许多限制可以通过使用几种生物的混合物来缓解或解决，包括代谢负荷和可以在单个细胞中包含和优化的外源元素的数量。这项研究的长期目标是产生合成微生物联合体，可作为多种生物处理应用的通用平台，如化学合成和生物修复。这种策略的灵感来自于自然发生的微生物群落。这些无处不在的群落由多个种群组成，它们共存，并进行复杂的化学过程和生理功能，使群落得以生存。细胞间的通讯，或微生物群体感应，对协调微生物群体的行为至关重要。当前项目的总体目标是设计新的基于群体感应的组件和系统，这些组件和系统将在革兰氏阴性和革兰氏阳性生物体中实现依赖细胞间通信的基因表达，并使用这些系统建立一个协调的多物种微生物群落。更广泛的影响：作为该项目的外延部分，PI将为K-12学生制定一个关于微生物群落的计划，旨在使学生深刻认识到这些群落在人类健康和生物技术中所起的重要作用。PI还将为研究生制定一项科学推广计划，重点是指导，并寻求增加女性在工程学院职位上的数量。综合研究和教育计划将教育本科生和研究生使用蛋白质工程和合成生物学。学生将接触到一种不断发展的、跨学科的科学研究方法，这将使他们为解决化学工程和生物技术中的复杂问题做好准备。

The biosynthesis of compounds of industrial importance often requires engineering and optimization of complex metabolic pathways. Traditionally, these processes have employed a clonal population of recombinant microbes such as E. coli or yeast. There are many limitations of using a single population that could be alleviated or addressed by using a mixture of several organisms, including metabolic load and the number of exogenous elements that can be contained and optimized in a single cell. The long-term goal of this research is to generate synthetic microbial consortia that can be used as a generic platform for diverse bioprocessing applications, such as chemical synthesis and bioremediation. This strategy is inspired by naturally occurring microbial consortia. These ubiquitous communities consist of multiple populations that coexist and carry out complex chemical processes and physiological functions to enable survival of the community. Cell-cell communication, or microbial quorum-sensing, is essential for coordinating the behavior of the microbial populations. The overall objective of the current project is to engineer new quorum sensing-based components and systems that will enable cell-cell communication dependent gene expression in both Gram-negative and Gram-positive organisms and to use these systems to establish a coordinated multi-species community of microbes.Broader impacts: For the outreach component of this project, the PI will develop a program for K-12 students on microbial communities that seeks to impress upon students the important roles such communities play in human health and biotechnology. The PI will also develop a scientific outreach program for graduate students that focuses on mentoring and seeks to increase the number of women in engineering faculty positions. The integrated research and educational plan will educate undergraduate and graduate students in the use of protein engineering and synthetic biology. Students will be exposed to an evolving, interdisciplinary approach to scientific research that will prepare them to solve complex problems in chemical engineering and biotechnology.