項目類別：國家自然科學基金
項目編號：31270150
項目規模：面上項目
參與人員：楊光（主持）張祥林 肖林 臧珊珊 黃琳 李瑩 孫臻 吳斌 黃威
起止日期：2013年1月-2016年12月
自然界中微生物種類極為豐富，尺寸涵蓋了納米級與微米級，是可用于納米、微米以及多層次跨尺度加工的天然“基本單元”和“底盤細胞”。本項目立足于構建用于定位操縱和可控裝配微生物活體“細胞工廠”的新方法，重點開拓和發展微流控和(或)微生物打印技術該兩項新技術。以釀酒酵母和大腸桿菌為模式菌種，木醋桿菌和肝素黃桿菌為功能菌種，誘發其特有的生物學功能，通過微生物微納米機器人進行受控自組裝，研究影響微生物的運動行為的調控因素，揭示微生物定位調控原理和多層次精細結構的形成機制。通過該方法可以設計特定的個性化微環境，探尋微生物的個體生長、代謝與行為模式。還可通過對微生物培養基的設計和打印，實現對大規模發酵過程的培養基優化，將傳統的正交實驗分析、響應面實驗分析手段芯片化。此外，通過多層次組裝，可設計和構筑復雜體系的微生物群落，為微生物反應器的設計、大規模生物煉制的調控提供理論依據和技術支撐。
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.