Assay Development Platforms

合成生物学试图模拟和构建自然界中不存在的生物成分，功能和生物体，并重新设计现有的生物系统以执行新的功能。从头构建大型复杂的遗传电路或代谢途径将使我们能够例如编程干细胞分化，检测癌细胞的多种变化，或设计细胞工厂以生产全新的药物或更绿色的化学品和生物燃料。在实验台上设计细胞的传统方法本质上是缓慢和昂贵的。自动化和工业化减少了开发时间，并且中到高通量过程的规模经济可以降低生物体开发的成本，使努力民主化，并允许能够进行这种复杂的生物体工程的学术团体和行业的数量扩大。为了实现我们对合成生物学的雄心壮志，我们需要使能技术，这些技术不仅可以为合成DNA的设计、构建和整合提供稳健、可靠和具有成本效益的方法，我们还需要了解组分或途径与宿主的相互作用，并捕获报告合成部分和途径性能的整体数据集，细胞生长和健康。最初的BBSRC投资（BBM00029X1和BBM00094X1）帮助建立了两个DNA合成中心，爱丁堡基因组铸造厂（EGF，位于生物科学学院）和利物浦基因磨坊（LGM，位于CGR基因组研究中心）提供DNA设计，合成和大基因构建体（高达1Mbp）的验证。然而，我们需要进一步扩大我们的能力，包括高通量检测开发，适合于评估DNA构建体是否在宿主细胞中提供所需的输出（即表型）。在这里，我们请求资本设备的支持，这将使我们能够建立多个平行的中等通量测定细胞的健康，功能和生产力。除了这些平台，我们还开发了用于自动化和分析的软件工具，以及将这些数据与设计和制造流程集成的软件。这将提供所需的数据，为未来设计精细的DNA构建体提供信息，加快设计构建测试周期，提高效率并降低合成生物学应用的应用成本。最终，这将有助于推动市场的增长，而不是从合成生物学中受益，并为DNA合成中心的初始投资增加价值。

Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature and to redesign existing biological systems to perform new functions. The construction de novo of large and complex genetic circuits or metabolic pathways will enable us to for example, program stem cell differentiation, detect multiple changes in cancer cells, or engineer cell factories to produce completely novel drugs or greener chemicals and biofuels. The conventional approach of engineering cells at the bench is inherently slow and expensive. Automation and industrialization reduce development time and the economies of scale of medium to high throughput processes can reduce the cost of organism development democratising the endeavour and allowing an expansion in the number of academic groups and industries that can undertake such complex organism engineering. To realise our ambitions for synthetic biology we need enabling technologies that can not only provide robust, reliable and cost effective methodologies for the design, construction and incorporation of synthetic DNA we need to understand the interaction of the component or pathway with the host and capture holistic datasets that report back on synthetic part and pathway performance, cell growth and health.The initial BBSRC investment (BBM00029X1 andBBM00094X1) has helped found two DNA synthesis centres, the Edinburgh Genome Foundry (EGF, based in the School of Biological Sciences) and Liverpool GeneMill (LGM, based within the Centre for Genomic Research CGR) offering DNA design, synthesis and validation of large gene constructs (up to 1Mbp). However, we need to further expand our capabilities to include high throughput assay development suited to assessing whether the DNA construct delivers the desired output (i.e. phenotype) in the host cell. Here we request support for capital equipment that will enable us to set up multi parallel medium throughput assays for cell health, function and productivity. Alongside these platforms we build the software tools for automation and analysis, together with software to integrate this data with the design and fabrication pipelines. This will provide the data needed to inform the future design of refined DNA constructs, accelerate the design build test cycle, improve efficiency and reduce the cost of application of synthetic biology applications. Ultimately this will help drive growth of the markets than can benefit from synthetic biology and add value to the initial investment in the DNA synthesis centres.