Engineering Fellowships for Growth: Advanced synthetic biology measurement to enable programmable functional biomaterials

合成生物学通过将工程设计原则严格应用于我们使用生物系统的方式来加速新生物技术的研究和开发。合成生物学最突出的应用是合理修改和重新设计微生物等活生物体，以便在能源生产，生物材料，生物医学，药物生产和食品技术等部门进行新的有效利用。开发和应用合成生物学的关键是合成生物学设计的严格量化，建模和分析。通过使用这种工程框架，研究人员旨在预测工程生物系统将如何运作。尽管取得了许多成功，但仍然很难预测当新的合成遗传信息添加到这些宿主细胞时工程细胞的行为。合成生物学正向工程的高失败率的关键是缺乏关于部件和设备的高质量数据。如果没有一个完整的数据集报告生物部件在其宿主细胞中的性能，就很难预测它在复杂设计中的表现。该项目中提出的工作旨在通过开发一种新的工作流程来解决这一问题，以便在细菌宿主细胞中实现数千种不同部件和设备时获得更丰富的数据集。为了实现这一目标，将建立一个筛选工作流程，首次将体外原型设计与体内分析和质谱分析相结合，以同时捕获合成生物学设备设计如何影响基因表达，表达负荷和宿主细胞健康，能量和生长。并行测量这些多个参数将极大地丰富预测模型，并且理想地将导致对性能特征（例如生长速率和突变可能性）的稳健的计算机模拟预测。在该项目中，将专门为此任务开发建模，并将引入质谱法作为最先进的测量工具。虽然这项研究将产生非常广泛的影响，并加速合成生物学的许多不同的未来应用，但在这个项目中，它将专门用于解决高价值的生物材料应用，如果没有这项工作提供的强大工程基础，就不太可能成功。对于该项目的这一部分，基因表达和生长的预测将用于表达工程微生物和微生物财团中不同功能蛋白质的文库，然后可以将其聚合在一起，以产生具有可编程催化和材料特性的多蛋白生物材料。例如，通过将丝蛋白与生物聚合物中的脂肪酶结合，可以实现自清洁织物等先进材料。虽然这项材料工作旨在展示该项目中开发的基础方法，但毫无疑问，它将在从时尚和制造到医学的各种商业，工程和研究领域带来许多令人兴奋的应用和新行业。

Synthetic biology accelerates the research and development of new biotechnologies by rigorously applying engineering design principles to the way we work with biological systems. The most prominent application of synthetic biology is the rational modification and redesign of living organisms like microbes for new efficient use in sectors such as energy production, biomaterials, biomedicine, drug production and food technology. Crucial to developing and applying synthetic biology is the rigorous quantification, modelling and analysis of synthetic biology designs. By using this engineering framework researchers aim to predict how engineered biological systems will operate.Despite many successes, it is still difficult to predict how engineered cells behave when new synthetic genetic information is added to these host cells. Key to the high failure rates in forward engineering in synthetic biology is the lack of high-quality data available on parts and devices. Without a holistic dataset reporting on performance of a biological part in its host cell, it is difficult to predict how it will behave when included in complex designs. The work proposed in this project seeks to address this by developing a novel workflow to obtain a richer-dataset on thousands of different parts and devices as they are implemented in bacterial host cells. To achieve this goal, a screening workflow will be established, that for the first time incorporates in vitro prototyping, with in vivo assaying and mass-spectrometry profiling to simultaneously capture how synthetic biology device design affects gene expression, expression load and host cell health, energy and growth. Measuring these multiple parameters in parallel will greatly enrich predictive models and ideally will lead to robust in silico predictions on performance characteristics such as growth rate and mutation likelihood. In this project, modelling will be developed specifically for this task and mass spectrometry will also be introduced as a state-of-the-art measurement tool. Both are new frontiers for synthetic biology.While this research will have a very wide impact and accelerate the many different future applications of synthetic biology, in this project it will be specifically used to tackle a high-value biomaterials application that would be unlikely to succeed without the strong engineering foundations this work provides. For this part of the project, predictions of gene expression and growth will be used to express a library of different functional proteins in engineered microbes and microbial consortia that can then be polymerised together to generate polyprotein biomaterials with programmable catalytic and material properties. For example, by combining silk proteins with lipase enzymes in biological polymers, advanced materials such as self-cleaning fabrics can be realised. While this materials work is intended as a showcase for the foundational methods developed in this project, it will no doubt lead to many future exciting applications and new industries in a rich variety of commercial, engineering and research sectors, from fashion and manufacturing to medicine.