Engineering a Competitive Advantage using Synthetic Biology and Microfluidic Technology

该项目结合合成生物学、微流控技术和计算建模，探索动态环境中三种模式生物的代谢网络，研究形成竞争增长优势的进化过程。人工合成的遗传振荡器将控制必需代谢酶在大肠杆菌和聚球藻(一种蓝藻)中的表达，并将这些工程生物在周期性变化的环境中的生长特征与野生型、非转基因生物进行比较。在酵母方面，合成生物学和微流控技术将被用来“进化”一个特征良好的新陈代谢网络，显微镜将被用来识别在动态环境中赋予生长优势的变化。建模和实验方法的结合将使人们深入了解如何通过工程或自然进化过程修改生物体，使它们在多变的环境中获得生长优势。更广泛的影响：对微生物进化的定量了解将有助于制定控制微生物感染的新战略。将与圣地亚哥联合学区和北县学区合作制定一项小学科学计划。项目人员和研究生将与小学教师合作，为研究生讲授与课堂课程相结合的动手实验科学课程做好准备。

This project combines synthetic biology, microfluidic technology, and computational modeling to probe metabolic networks in three model organisms in dynamic environments and to study the evolutionary process of developing a competitive growth advantage. A synthetic genetic oscillator will control expression of essential metabolic enzymes in E. coli and Synechocystis (a cyanobacterium), and the growth characteristics of these engineered organisms in a periodically changing environment will be compared to wildtype, non-modified organisms. In yeast, synthetic biology and microfluidic technology will be used to "evolve" a well-characterized metabolic network and microscopy will be used to identify changes that confer a growth advantage in a dynamic environment. The combination of modeling and experimental approaches will provide insight into how organisms can be modified, either through engineered or natural evolutionary processes, to give them a growth advantage in fluctuating environments. Broader Impacts: A quantitative understanding of microbial evolution will contribute to the development of new strategies to control microbial infections. An elementary school science program will be developed in partnership with the San Diego Unified and North County school districts. Project personnel and graduate students will work with elementary school teachers to prepare the graduate students to teach hands-on experimental science lessons that are integrated with the classroom curriculum.