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微生物活体操纵与可控装配新方法的构建及其应用(Developing New Methods and Application for Controllable Manipulation and Assembly of Living Microbe)
项目类别:国家自然科学基金
项目编号:31270150
项目规模:面上项目
参与人员:杨光(主持)张祥林 肖林 臧珊珊 黄琳 李莹 孙臻 吴斌 黄威
起止日期:2013年1月-2016年12月

自然界中微生物种类极为丰富,尺寸涵盖了纳米级与微米级,是可用于纳米、微米以及多层次跨尺度加工的天然“基本单元”和“底盘细胞”。本项目立足于构建用于定位操纵和可控装配微生物活体“细胞工厂”的新方法,重点开拓和发展微流控和()微生物打印技术该两项新技术。以酿酒酵母和大肠杆菌为模式菌种,木醋杆菌和肝素黄杆菌为功能菌种,诱发其特有的生物学功能,通过微生物微纳米机器人进行受控自组装,研究影响微生物的运动行为的调控因素,揭示微生物定位调控原理和多层次精细结构的形成机制。通过该方法可以设计特定的个性化微环境,探寻微生物的个体生长、代谢与行为模式。还可通过对微生物培养基的设计和打印,实现对大规模发酵过程的培养基优化,将传统的正交实验分析、响应面实验分析手段芯片化。此外,通过多层次组装,可设计和构筑复杂体系的微生物群落,为微生物反应器的设计、大规模生物炼制的调控提供理论依据和技术支撑。

 

Microbe is extremely abundent in nature, the size of which has a very wide coverage from nano- to micro-scale making it suitable to be processed at multi-scale level as natural " building blocks " and "chassis cell". Based on the urgent need of micro/nano bio-manufacture of microorganism, four controlling methods-- i.e. molecular template, magnetic control, microfluidics, and bio- printing --for the process suitable for microbe have been proposed to dip into the behavioral mode of microorganism and design new micro/nano functional materials by controlling directed movement and ordered arrangement of microorganism living cells. To our best knowledge, it is a promising and challenging project with originality in the field of microorganism.
This project aims at developing new methods and techniques of micro/nano manufacture based on physical/chemical/biological principles as well as establishing new ways for controlled manipulation and controllable living microorganism “cell factory”, especially focusing on exploring two new techniques—micro-fluidic and bio-printing. Through combinational and synergistic effort, it is expected be able to control the microorganism and its product from molecular to nano/micro level. Thus, the application prospect is extremely attractive, and it is highly promising to open up a new field of micro/nano manufacturing with living microorganism.
Specifically, using Saccharomyces cerevisiae and Escherichia coli as mode strains and Acetobacter xylins and Flavobacterium heparinum as function strains to investigate regulatory factors affecting the movement behavior of microorganism, nano-scale effect, surface/interfacial effect and biological effect during the biological manufacture process of microbial micro/nano robot self-assembly to reveal the underlying principle of microorganism orientation and mechanism of formation of fine structure at multi-level by inducing their unique biological function.
Hopefully, this new way will facilitate specific design of individual microenvironment, exploration of the growth, metabolism and behavior of microorganism. It is not only probable to study the behavior of the same microorganism in different micro environment, but also possible to reveal the interaction between different microbial individuals. Furthermore, optimization of culture medium for massive fermentation as well as assembly of the traditional orthogonal experiment analysis and response surface analysis into small chips can be achieved by designing and printing of the culture medium of microorganism. Finally, it will provide theoretical basis and technique support for the design of microorganism reactor and regulation of massive bio-refinery by multi-level construction of complex microorganism community.