Sandpit: The Programmable Rhizosphere

几个世纪以来，人类一直在努力控制和利用生物来达到自己的目的。农业实践的发展是为了使动植物的产量最大化。最近，微生物系统已被操纵，以增加其在食品，生物技术和酿造业的效用。许多这些变化是通过育种和改良农艺性状的机会选择实现的。基因工程的最新发展使科学家们能够应用精确的扰动，从而在生物体中产生有益的变化。然而，生物系统的复杂性使得使用传统的基因工程技术手动设计和实施可预测地产生预期表型的大变化变得困难。我们合成DNA的能力远远超过了我们设计新遗传系统的能力。合成生物学为合理设计和可复制制造生物电路提供了希望，这些电路可用于在生物体中引入所需的功能。这种方法的一个主要前提是，应该将工程原理应用于设计模块化电路，这些电路由特性良好的部件和组件组成，使用定义的组成规则。迄今为止，还缺乏一个使这种方法能够用于生物学工程的框架。在这个项目中，我们建议开发这样一个框架，以及一个独特的新DNA部分库。具体来说，我们建议解决如何设计生物（如微生物和植物）中的细胞电路以可预测和稳健的方式自组织并与其他生物相互作用的问题。为此，我们将开发新的数学和计算方法，自动将所需功能的定量描述转换为在细菌中实现该功能的电路设计。此外，我们将生成DNA部分的集合，这些DNA部分将允许在不同细胞群或生物体之间构建新的通信通道，以及营养物质共生交换的途径。在许多情况下，改善调节细胞的能力，形成稳定的新生态，将有益于人类。这些应用范围从组织工程到生物修复、生物技术和生物能源。在这个项目中，我们选择关注植物和土壤细菌之间的关系，这些细菌通常生活在根系旁边。我们希望设计模式细菌和模式植物之间的交流，以允许协商和建立一种新的共生关系。该系统将在改善可持续农业、生物生产和粮食安全方面有许多应用，例如改善土壤利用、抗虫害、杂草抑制和创造能够固氮的新作物植物。

Humans have striven for centuries to control and exploit living organisms for their own purposes. Agricultural practices have been developed to maximise the yield of plants and animals. More recently, microbial systems have been manipulated to increase their utility in the food, biotech and brewing industries. Many of these changes have been achieved through breeding and chance selection for improved agronomic characters. Recent developments in genetic engineering have allowed scientists to apply precise perturbations that lead to beneficial changes in an organism. However, the complexity of biological systems makes it difficult to manually design and implement large changes that predictably produce an intended phenotype using conventional genetic engineering techniques. Our ability to synthesise DNA far outstrips our ability to design new genetic systems. Synthetic Biology holds the promise of rational design and reproducible fabrication of biological circuits that can be used to introduce a desired function in an organism. One of the main premises of this approach is that engineering principles should be applied to the design of modular circuits from well-characterized parts and components, using defined composition rules. A framework that enables this approach to the engineering of biology has, to date, been lacking. In this project, we propose to develop such a framework, and a unique library of new DNA parts. Specifically, we propose to tackle the problem of how cellular circuits in organisms (such as microbes and plants) can be designed in to self-organise and interact with other organisms in a predictable and robust fashion. To this end we will develop novel mathematical and computational approaches that automatically transform a quantitative description of a desired function into a circuit design that implements this function in bacteria. In addition we will generate a collection of DNA parts that will allow the construction of new channels of communication between different cell populations or organisms, and the pathways for symbiotic exchange of nutrients. There are many situations where improvements in the ability to regulate cells, and to form stable new ecologies, would be of benefit to humans. These range from applications in tissue engineering through to bioremediation, biotechnology and bioenergy. In this project we have chosen to focus on the relationship between plants and soil bacteria that normally live alongside the root system. We wish to engineer communication between a model bacterium and model plant, to allow negotiation and establishment of a new symbiotic relationship. The system would have many applications for improvements in sustainable agriculture, bioproduction and food security, such as improvements in soil use, pest resistance, weed suppression and creation of new crop plants capable of nitrogen fixation.