Engineered security systems for environmental synthetic biology

这项研究旨在提供推进合成生物学这一令人兴奋的新课题所需的关键部分，以便安全可靠地实现生物技术在健康、环境和能源需求方面的应用。自2000年以来，合成生物学这一新领域通过应用工程学原理、设计、模拟和测试，推动了现有的基因改造科学。这种方法使我们能够通过修改安全的微生物来执行新的任务，包括计算，多输入环境传感以及有效生产药物和生物能源，从而可预见地创造出令人兴奋的新技术。虽然合成生物学的研究取得了迅速的成功，但这项工作转化为社会使用的真实的应用一直是有限的;我们可以为爆炸物，砷和其他环境污染物建立优秀的细胞生物传感器，但没有一个实际投入使用。很大程度上，这是因为合成生物学创造了转基因生物（GMOs），而这些转基因生物的部署是一种监管风险。主要的担忧是，这些转基因生物的工程DNA将通过一种称为水平基因转移（HGT）的过程转移到自然微生物中，这将破坏自然生态系统。当我们研究像大肠杆菌这样的细菌时，这种担心尤其恰当。在这些生物中，合成生物学家通常将他们的系统设计为维持在称为质粒的DNA环上，这些质粒易于使用，但也迅速在细菌中共享，并且通常赋予对抗生素的抗性。为了克服这一障碍，并允许合成生物学在环境中的安全应用，本研究旨在使用合成生物学技术构建一种新的质粒系统，该系统固定在预期细胞上，不会产生抗生素耐药性，并抵抗基因水平转移到天然细菌中。这一发展将包括一种测定HGT的方法和一种预测所涉及的关键因素的模型模拟。

This research seeks to provide crucial parts needed to advance the exciting new topic of synthetic biology in order to safely and securely realise biotechnology applications for health, environment and energy needs. Since 2000, the new field of synthetic biology has advanced the existing science of genetic modification by applying principles of engineering; design, simulation and testing. This approach has allowed us to predictably create exciting new technologies by modifying safe microbes to perform new tasks including computation, multi-input environmental sensing and efficient production of medicinal drugs and bioenergy. While research success in synthetic biology has been rapid, the transfer of this work into real applications used by society has been limited; we can build excellent cell biosensors for explosives, arsenic and other environmental pollutants but none have actually been put to use. Largely this is because synthetic biology creates genetically modified organisms (GMOs) and these are a regulatory hazard to deploy. The major concern is that engineered DNA of these GMOs will be transferred to natural microbes by a process called horizontal gene transfer (HGT) and that this will disrupt natural ecosystems. This concern is particularly apt when we work with bacteria such as E. coli, as in these organisms synthetic biologists typically engineer their systems to be maintained on DNA circles called plasmids, which are easy to work with but also rapidly shared among bacteria and usually confer resistance to antibiotics. To overcome this hurdle and allow safe application of synthetic biology in the environment, this research aims to use synthetic biology techniques to construct a new kind of plasmid system that is secured to the intended cell, does not confer antibiotic resistance and resists horizontal gene transfer into natural bacteria. The development of this will include an assay to measure HGT and a model simulation to predict the key factors involved.