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

合成生物学可以分为两种截然不同的方法。第一种是自上而下的方法，使用代谢和基因工程技术修改细胞。第二个是关于自下而上构建膜结合的微系统--人造细胞--它在形式和功能上类似于生物细胞。目前最先进的技术包括使用脂囊作为底盘，通过生物分子机械来实现功能，从而可以模拟细胞过程。到目前为止，这些方法基本上是在彼此孤立的情况下发展起来的。该项目的目的是通过使用跨空间通信在种群水平上将合成细胞与工程生物细胞化学联网来弥合这一分歧。在这个项目中，我们将设计一套刺激响应型合成细胞，它可以在活的大肠杆菌中诱导DNA程序激活，以响应外部刺激。人造细胞将充当人类使用者和活细胞之间的中介，能够将信号(热、光、磁场、声场)转化为活细胞可以理解(IPTG)和作用(合成感兴趣的蛋白质)的语言。生物技术中的这一新概念框架将允许以一种仅使用生命系统不可能的方式创建响应系统，这一战略直接与CDT的职权范围相一致。这种方法将有效地扩大细菌的感官范围，使其能够对与它们进化而来的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.