Engineered security systems for environmental synthetic biology

环境合成生物学工程安全系统

• 批准号: BB/J019720/1
• 负责人: Thomas Ellis
• 金额: $ 15.3万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ019720%2F1
• 关键词: Engineered; security; systems; environmental; synthetic

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.

这项研究旨在提供推进令人兴奋的合成生物学新课题所需的关键部分，以便安全可靠地实现满足健康、环境和能源需求的生物技术应用。自2000年以来，合成生物学这一新领域通过应用工程学原理推进了现有的基因改造科学；设计、模拟和测试。这种方法使我们能够通过修改安全微生物来执行新任务，包括计算、多输入环境传感以及药物和生物能源的高效生产，从而可预见地创造出令人兴奋的新技术。尽管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实际应用的程度却受到限制。我们可以构建优秀的细胞生物传感器来检测爆炸物、砷和其他环境污染物，但实际上还没有投入使用。这在很大程度上是因为合成生物学创造了转基因生物（GMO），而这些生物体的部署存在监管风险。人们主要担心的是，这些转基因生物的工程 DNA 将通过称为水平基因转移 (HGT) 的过程转移到天然微生物中，这将破坏自然生态系统。当我们研究大肠杆菌等细菌时，这种担忧尤其恰当，因为在这些生物体中，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 DNA 环很容易使用，但也能在细菌之间快速共享，并且通常赋予对抗生素的耐药性。为了克服这一障碍并允许合成生物学在环境中安全应用，本研究旨在利用合成生物学技术构建一种新型质粒系统，该系统固定在目标细胞上，不会赋予抗生素抗性，并且能抵抗水平基因转移到目标细胞中。天然细菌。该项目的开发将包括测量 HGT 的测定方法和预测所涉及关键因素的模型模拟。

项目成果

GeneGuard: A modular plasmid system designed for biosafety.

GeneGuard：专为生物安全而设计的模块化质粒系统。

• DOI: http://dx.10.1021/sb500234s
• 发表时间: 2015
• 期刊: ACS synthetic biology
• 影响因子: 4.7
• 作者: Wright O

Building-in biosafety for synthetic biology.

合成生物学的内置生物安全性。

• DOI: 10.1099/mic.0.066308-0
• 发表时间: 2013-07-01
• 期刊: Microbiology
• 影响因子: 1.5
• 作者: O. Wright;G. Stan;T. Ellis
• 通讯作者: T. Ellis