Analysis, Design and Control of Biological Circuits and Bio-Inspired Networks

通过细胞网络控制信息流的监管架构是至关重要的细胞行为的系统级的理解和设计合成生物电路的工程方法的发展。这些监管架构由不同的监管机制组成，这些机制在不同的时间尺度上发挥作用，并同时发挥作用，以创建复杂的控制系统，调节组分相互作用的动力学。通过开发用于分析和设计细胞中复杂调控网络的技术，我们的目标是更好地了解细胞如何调节其功能，以实现诊断和生物合成应用的生物电路工程，并提供网络科学的新技术，使人们能够理解和构建复杂的网络，在存在高度不确定性的情况下提供鲁棒的行为。PI和Murray教授的长期目标是开发一种架构理论，可用于理解和设计复杂的网络控制系统。我们相信，我们开发的理论和工具不仅与细胞生物学相关，而且与各种规模和复杂程度的工程系统相关。所有这些类别的系统的共同特点是无处不在的使用互连和反馈，其操作的鲁棒性和脆弱性（RYF）的性质，以及缺乏当前的工具来理解所有，但其操作的选定部分。为达致这个长远目标，我们集中研究有系统地分析生物功能的各种调控形式所需的理论、工具和仪器。Murray教授结合模型和实验，探讨了多重同步反馈机制在细胞中提供高性能操作的作用，并对参数变化保持稳健。在过去的一年里，他专注于实验和基于模型的表征酵母中半乳糖电路的超敏感性，这提供了一个多机制调控策略的很好的例子。半乳糖基因开关是具有多个反馈回路的系统的一个例子，这些反馈回路相互作用以产生强大的生物功能。半乳糖被导入细胞，通过四阶段信号传导过程激活半乳糖调节子的转录。额外的理论工作有助于探索使用时间延迟作为设计元素来塑造生物分子系统的行为。

The regulatory architectures controlling information flow through cellular networks are critical to a systems-level understanding of cellular behaviour and to the development of engineering methods for designing synthetic biological circuits. These regulatory architectures are comprised of the diverse regulatory mechanisms that act at different time scales and act simultaneously to create complex control systems regulating the kinetics of component interactions. By developing techniques for the analysis and design of complex regulatory networks in cells, we aim to better understand how cells regulate their function, to enable the engineering of biological circuits for diagnostic and biosynthetic applications, and to provide new techniques in network science that allow understanding and construction of complex networks that provide robust behaviour in the presence of high levels of uncertainty.The long-term goal of the PI and Prof Murray is to develop a theory of architecture that can be used to understand and design complex networked control systems. We believe that the theory and tools that we develop will be relevant not only to the biology of the cell, but also to engineering systems at a variety of scales and levels of complexity. The common features of all of these classes of systems are the ubiquitous use of interconnection and feedback, the robust yet fragile (RYF) nature of their operation, and the lack of current tools to understand all but selected parts of their operation. To pursue this long-term goal, we have focused on the theory, tools and devices required to systematically analyse various forms of regulation of biological function.Using a combination of modelling and experiments, Prof Murray has explored the role of multiple, simultaneous feed-back mechanisms for providing high performance operation in cells, with robustness to parametric variations. In the past year, he has focused on experimental and model-based characterization of ultra-sensitivity of the galactose circuitry in yeast, which provides an excellent example of a multi-mechanism regulatory strategy. The galactose genetic switch is an example of a system with multiple feedback loops that interact to create robust biological function. Galactose is imported into the cell to activate transcription of the galactose regulon through a four-stage signalling process. Additional theoretical work has helped explore the use of time delays as a design element for shaping the behaviour of biomolecular systems.