Jang Seunghee S, Oishi Kevin T, Egbert Robert G, Klavins Eric
Department of Electrical Engineering, University of Washington, Seattle, WA 98195, USA.
ACS Synth Biol. 2012 Aug 17;1(8):365-74. doi: 10.1021/sb300034m. Epub 2012 Jul 31.
Recent advances in the design and construction of synthetic multicelled systems in E. coli and S. cerevisiae suggest that it may be possible to implement sophisticated distributed algorithms with these relatively simple organisms. However, existing design frameworks for synthetic biology do not account for the unique morphologies of growing microcolonies, the interaction of gene circuits with the spatial diffusion of molecular signals, or the relationship between multicelled systems and parallel algorithms. Here, we introduce a framework for the specification and simulation of multicelled behaviors that combines a simple simulation of microcolony growth and molecular signaling with a new specification language called gro. The framework allows the researcher to explore the collective behaviors induced by high level descriptions of individual cell behaviors. We describe example specifications of previously published systems and introduce two novel specifications: microcolony edge detection and programmed microcolony morphogenesis. Finally, we illustrate through example how specifications written in gro can be refined to include increasing levels of detail about their bimolecular implementations.
在大肠杆菌和酿酒酵母中合成多细胞系统的设计与构建方面的最新进展表明,利用这些相对简单的生物体实现复杂的分布式算法或许是可行的。然而,现有的合成生物学设计框架并未考虑生长中的微菌落的独特形态、基因回路与分子信号空间扩散的相互作用,或者多细胞系统与并行算法之间的关系。在此,我们引入了一个用于多细胞行为规范和模拟的框架,该框架将微菌落生长和分子信号传导的简单模拟与一种名为gro的新规范语言相结合。该框架使研究人员能够探索由单个细胞行为的高级描述所诱导的集体行为。我们描述了先前发表系统的示例规范,并引入了两个新颖的规范:微菌落边缘检测和程序化微菌落形态发生。最后,我们通过示例说明如何对用gro编写的规范进行细化,以纳入关于其双分子实现的越来越多的细节。