Control Engineering Inspired Design Tools for Synthetic Biology

受控制工程启发的合成生物学设计工具

• 批准号: EP/I031944/1
• 负责人: Antonis Papachristodoulou
• 金额: $ 46.27万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI031944%2F1
• 关键词: Control; Engineering; Inspired; Design; Tools

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)).

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。这种能力与世纪中期电气工程的技术进步并行，这种新技术的潜力正在全世界得到认可。这个新的领域，它的名字合成生物学，已被描述为生物工程。这一领域是在它的婴儿期，不可避免地面临着一些挑战。例如，当前的实践集中在通过将几个被认为具有充分特征的组件/部件放在一起来设计非常简单的电路。在实施时，这些电路几乎从未按预期工作，尤其是因为单元内存在的不确定性/噪声、与单元内其他电路的串扰水平以及测量和实施技术带来的限制。事实上，设计/重新设计过程更多的是一种艺术，而不是一种技术，因为它主要基于直觉，而且在设计阶段不考虑不确定性/噪声和串扰。为了使合成生物学发挥其潜力，并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于调整电路行为的生物“旋钮”，以及这些电路将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，生物网络的分析和设计。我们的目标是开发一个新的设计周期，灵感来自控制工程实践，但适应合成生物学的约束和需求，以可预测的方式进行生物系统的设计。这个工程周期将在三个具有根本重要性的系统上举例说明，即，振荡器、滤波器和开关的目标是优化其性能，使其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个机构的工程和生命科学系进行（牛津大学、剑桥大学和伦敦帝国理工学院），并将得到国际项目合作伙伴的外部支持，这些合作伙伴将在该项目上开展合作。（加州理工学院（CalTech）、苏黎世Eidgenossische Technische Hochschule（ETH）和马萨诸塞州理工学院（MIT））。

项目成果

Generalised absolute stability and sum of squares

广义绝对稳定性和平方和

• DOI: 10.1016/j.automatica.2013.01.006
• 发表时间: 2013
• 期刊: Automatica
• 影响因子: 6.4
• 作者: Hancock E

An optimization-based method for bounding state functionals of nonlinear stochastic systems

• DOI: 10.1109/cdc.2016.7799088
• 发表时间: 2016-12
• 期刊: 2016 IEEE 55th Conference on Decision and Control (CDC)
• 作者: M. Ahmadi;Andreas W. K. Harris;A. Papachristodoulou

A single phosphatase can convert a robust step response into a graded, tunable or adaptive response

• DOI: 10.1099/mic.0.066324-0
• 发表时间: 2013-07-01
• 期刊: MICROBIOLOGY-SGM
• 影响因子: 2.8
• 作者: Chang, Yo-Cheng;Armitage, Judith P.;Wadhams, George H.
• 通讯作者: Wadhams, George H.

Engineering and ethical perspectives in synthetic biology. Rigorous, robust and predictable designs, public engagement and a modern ethical framework are vital to the continued success of synthetic biology.

• DOI: 10.1038/embor.2012.81
• 发表时间: 2012-06-29
• 期刊: EMBO REPORTS
• 影响因子: 7.7
• 作者: Anderson, James;Strelkowa, Natalja;Stan, Guy-Bart;Douglas, Thomas;Savulescu, Julian;Barahona, Mauricio;Papachristodoulou, Antonis
• 通讯作者: Papachristodoulou, Antonis

Tuning the dials of Synthetic Biology.

• DOI: 10.1099/mic.0.067975-0
• 发表时间: 2013-07
• 期刊: Microbiology (Reading, England)
• 作者: Arpino JAJ;Hancock EJ;Anderson J;Barahona M;Stan GV;Papachristodoulou A;Polizzi K
• 通讯作者: Polizzi K