生物结构和图案的形成是现代科学中最重大的课题之一。传统的方法是利用遗传变异，生化分析来窥视其中的奥秘，我们称之为“格物致知”。但这并不能达到完全理解生物图案的形成的目的。这个重大课题的进步有赖于新思想和新方法的建立。其中一个重要的新方法是通过人工设计建造新的图案来理解其中的原理，我们称之为“建物致知”。最近，我们通过合成生物学建造了一个新的基因回路，使得单一的大肠杆菌群体在宏观水平上自发产生了新颖的生物图案。我们并通过理论分析揭示了一个新的图形形成原理。这些工作最近发表在《科学》和《物理评论快报》上。..生物图案往往是由不同细胞种群相互作用形成的。在本项目里，我们将设计多个大肠杆菌品系，使其有不同的相互作用。这些品系将被用于探测细胞群体相互作用和图案生成的关系。本研究的实施将促进合成生物学和物理学的进一步结合和新方法学的建立。其揭示的基本原理也将会适用于其他生物学团案的形成。

How biological structures or patterns are formed is one of the most fundamental questions in modern science. It involves intriguing processes and has been a recurrent topic that fascinated generations of scientists. The traditional approaches in the field are based on genetic mutagenesis and biochemical analysis, which can only reveal some specific aspects of the pattern formation process without giving a complete understanding. The underlying determinants are often buried in the overwhelmingly complex context so that a unified picture has yet to emerge. Our recent works on pattern formation took another approach: we designed and fabricated a genetic circuit to control the behavior of individual E. coli cells. This resulted in spontaneous formation of novel biological patterns in macro scale. Theoretical analysis subsequently revealed a novel principle of biological pattern formation and in turn directed further engineering of new patterns. These works were well-received and published in major scientific journals (Science and PRL)..Biological structures or patterns are often formed by several different cell populations that interact with each other. In this project, we will design and construct multiple E. coli strains. With various defined interactions, these strains will be used to investigate the relationship between cell population interactions and biological pattern formation. The current project also proposes to build an integrative approach by combining theoretical and experimental physics—to model and characterize accurately biological pattern forming systems—and synthetic biology—which opens up the possibility to control cell behavior through the design of specific genetic circuits. The successful implementation of this study will not only promote the further integration of synthetic biology and physics, and the establishment of the new methodology, but also reveal basic principles applicable to stem cells research, tissue engineering and artificial organ formation..

由多种细胞类型形成的生物结构和生物图案是普遍而基本的生物学现象。不同细胞类型之间的相互作用，如合作和竞争，在多细胞生物的进化和发展中发挥了关键作用。然而，由于有限的模式生物模型以及多细胞生物体的复杂性，不同细胞类型间的相互作用在生物图案形成过程中的潜在作用仍不清楚。在这项研究中，我们在大肠杆菌中构建了人工的相互作用系统，并发现和研究了这类相互作用所产生的新型生物图案。我们构建了两类基因回路以使得一类大肠杆菌的运动速度依赖于另一类大肠杆菌的当地密度。通过将来自Vibrio fischeri的LuxR / LuxI群体感应系统和来自铜绿假单胞菌的LasR / LasI群体感应分开表达于大肠杆菌菌株AMB1655，实现了两类大肠杆菌细胞的双向交流。我们发现，当改造后的细胞群体互相促进对方的运动，充分混合的两类细胞可以自发周期性地形成条纹斑图，并且两者的密度在条纹上呈现反相振荡，进而产生交替的条纹斑图。而当相互作用变成对两类细胞运动的相互抑制时，混合的细胞也可自发周期性地形成条纹斑图，但是两者空间分布变为同相振荡，进而产生共定位的条纹斑图。此研究结果揭示了通过在多细胞系统中交叉调控细胞群体的运动速度可能是多细胞生物图案形成和演化的潜在基本原理，其将对组织工程，器官形成和干细胞的研究有重要的启示作用。