Engineering synthetic cell 'translators' to mediate human-cell communication

合成生物学可以分为两种不同的方法。第一种是自上而下的方法，即使用代谢和基因工程技术对细胞进行修饰。第二个是关于自下而上构建膜结合的微系统-人工细胞-在形式和功能上类似于生物细胞。目前最先进的技术涉及使用脂质囊泡作为底盘，其用生物分子机制功能化，允许模拟细胞过程。到目前为止，这些方法在很大程度上是在相互孤立的情况下发展的。该项目的目的是通过使用空间通信在群体水平上将合成细胞与工程生物细胞化学联网来弥合这一鸿沟。在这个项目中，我们将设计一套刺激响应的合成细胞，可以诱导激活活大肠杆菌中的DNA程序。大肠杆菌对外界刺激的反应人工细胞将作为人类用户和活细胞之间的中介，能够将信号（热，光，磁场，声场）“翻译”成活细胞可以理解的语言（IPTG）并采取行动（合成感兴趣的蛋白质）。生物技术的这一新概念框架将允许以一种不可能单独使用生命系统的方式创建响应系统，这一战略与CDT的职权范围直接一致。这种方法将有效地扩大细菌的感觉范围，从而允许对与它们进化所能做出反应的线索完全不同的线索做出反应。

Synthetic biology can be divided into two distinct approaches. The first is the top-down approach, where cells are modified using metabolic and genetic engineering techniques. The second is concerned with the bottom-up construction of membrane-bound microsystems - artificial cells - that resemble biological cells in form and function. The current state-of-the-art involves using lipid vesicles as chassis that are functionalised with biomolecular machinery allowing cellular processes to be mimicked. Until now, these approaches have largely evolved in isolation from one another. The aim of this project is to bridge this divide by chemically networking synthetic cells with engineered biological ones on a population level using through-space communication. In this project we will design a suite of stimuli-responsive synthetic cells that can induce activation of a DNA programme in living E. coli in response to external stimuli. The artificial cells will act as intermediaries between a human user and a living cell, capable of 'translating' a signal (heat, light, magnetic field, acoustic field) into a language that living cells can understand (IPTG) and act upon (synthesizing a protein of interest). This new conceptual framework in biotechnology will allow the creation of responsive systems in a way that is not possible using living systems alone, a strategy that is directly aligned with the remit of the CDT. This approach will effectively lead to expanded sensory range of bacteria, allowing then to respond to cues that are entirely different from the ones they have evolved to respond to.