Control Engineering Inspired Design Tools for Synthetic Biology

最近的技术进步使我们能够操纵细胞内的电路并改变它们的行为。此外，我们现在可以在细胞内设计全新的电路。这种能力与20世纪中期电气工程的技术进步相媲美，这项新技术的潜力正在全世界得到认可。这个以合成生物学为名的新领域被称为生物学工程。这一领域尚处于起步阶段，不可避免地会面临一些挑战。例如，目前的实践集中在设计非常简单的电路，将几个被认为具有充分特征的组件/部件放在一起。当实现时，这些电路几乎从来没有像预期的那样工作，尤其是由于单元内存在的不确定性/噪声，单元内与其他电路的串扰水平以及测量和实现技术所带来的限制。事实上，设计/重新设计过程更像是一门艺术，而不是一种技术，因为它主要基于直觉，而且在设计阶段没有考虑不确定性/噪音和串扰。为了使合成生物学发挥其潜力，能够生产具有更丰富功能的大规模生物电路，设计周期需要考虑所有可用的生物“旋钮”，这些“旋钮”可以用来调整电路的行为，以及这些电路需要发挥作用的环境的不确定性。在这个项目中，我们提出了一个系统的设计方法，使用工程原理来分析和设计生物网络。目标是开发一种新的设计周期，灵感来自控制工程实践，但适应合成生物学的限制和需求，设计以可预测的方式运行的生物系统。这个工程周期将以三个重要的系统为例，即振荡器、滤波器和开关，其目标是优化它们的性能，使它们在不确定的环境中可靠地工作。这项研究将在参与这项研究的三所大学（牛津大学、剑桥大学和伦敦帝国理工学院）的工程和生命科学系进行，并将得到国际项目合作伙伴（加州理工学院（CalTech）、苏黎世理工学院（ETH）和麻省理工学院（MIT））的外部支持。

Recent technological advances allow us to manipulate the circuitry inside cells and to modify their behaviour. Moreover, we can now design entirely new circuits within cells. This ability parallels the technological advances in Electrical Engineering in the mid-20th century and the potential of this new technology is being recognised throughout the world. This new field, which goes under the name of Synthetic Biology , has been described as the Engineering of Biology .This field is in its infancy and inevitably faces several challenges. For example, current practice concentrates on the design of very simple circuits by putting together several components/parts that are believed to be characterised adequately. When implemented, these circuits almost never work as expected not least because of the uncertainties/noise that are present inside cells, the level of cross-talk with other circuits inside cells as well as the limitations posed by measurement and implementation technologies. In fact the design/redesign process is still more of an art rather a technology, in that it is mainly based on intuition and moreover, uncertainties/noise and crosstalk are not taken into account at the design stage. For Synthetic Biology to fulfil its potential and be able to produce large-scale biocircuits with richer functionality, the design cycle needs to take into consideration all available biological 'knobs' that could be used to tune the circuit's behaviour, as well as the uncertainties of the environment in which these circuits will need to function.In this project we propose a systematic design approach that uses engineering principles for the analysis and design of biological networks. The objective is to develop a new design cycle, inspired from control engineering practice but adapted to the constraints and needs of synthetic biology for the design of biosystems that behave in a predictable fashion. This engineering cycle will be exemplified on three systems of fundamental importance, i.e., oscillators, filters and switches with the goal of optimising their performance in such a way that they work reliably within uncertain environments. This research will be undertaken at Engineering and Life sciences departments in the three institutions involved in this research (the University of Oxford, the University of Cambridge and Imperial College London) and will be supported externally with international project partners who will collaborate on this project (California Institute of Technology (CalTech), Eidgenossische Technische Hochschule (ETH) Zurich, and the Massachusetts Institute of Technology (MIT)).