分子系统生物学与细胞发生动力学

系统生物学采用系统理论和实验生物技术、计算机数学模型等方法整合研究动态生物系统网络.生物系统的结构理论和生物系统技术,研究基因组——生物体复杂系统与细胞分子网络系统的动态结构发生与进化,分析基因组的逻辑程序和人工设计原理.细胞信号传导、基因调控网络、代谢反应链和基因反馈调控的自组织化人工设计和基因、基因链、基因组人工合成等系统生物工程开发,可用于复杂疾病机理分析、药物分子筛选和转基因表达系统的生物反应器、纳米生物计算机等.     

生物体系的多层次计算设计与合成生物学

合成生物学的核心思想是将现代工程学的原理与方法引入对生命系统的改造和构建中.生命活动覆盖从分子到细胞再到有机体等不同层次.合成生物学研究同样跨越了多个层次,例如,在分子层次进行生物元件和器件的设计和标准化、通过合成基因线路研究生物网络的设计和调控原理、在途径和网络层次进行细胞内代谢网络和代谢途径的人工设计改造等.本文一方面试图对与此有关的既有计算机模拟与设计方法加以总结和介绍,另一方面探讨这些不同层次的计算模拟与设计工具可应用于哪些方面的合成生物学问题,以及既有方法可能在哪些方向上还有比较大的发展潜力,能更好满足合成生物学研究需求.     

合成生物学的医学应用

合成生物学旨在基于工程学原理,通过人工合成生物调控元件、模块和基因调控网络等对细胞进行设计和改造,以实现细胞和生命体的定向演化.在医学研究中,合成生物学主要采用人工设计合成治疗性的基因回路,制备工程化细胞植入体内,纠正机体已发生缺陷的生物调控元件,以达到治疗疾病的目的.本文对合成生物学的兴起、发展及其在医学中的应用和研...     

动态应答人工生物系统研究进展

代谢和应答是生命的基本特征,自然界中的生命有机体的应答与调控是极度动态和时空精密的.复杂合成生物体系也应具有相应的应答调控特性.通过动态可控的元器件及人工调控系统,调控信息的流动使之对体内外环境动态应答,可用于对生命行为的理解与操纵.发展可与人体相互作用并动态应答的合成生物系统,也将为疾病的干预提供新的可能性.本文简要综述了近年来动态应答合成生物学器件与人工生物系统的研究进展.     

系统生物学与细胞发生系统动力学

系统生物学是系统理论和实验生物技术、计算机数学模型等方法整合的生物系统研究,系统遗传学研究基因组的稳态与进化、功能基因组和生物性状等复杂系统的结构、动态与发生演变等。合成生物学是系统生物学的工程应用,采用工程学方法、基因工程和计算机辅助设计等研究人工生物系统的生物技术。系统与合成生物学的结构理论,序列标志片段显示分析与微流控生物芯片,广泛用于研究细胞代谢、繁殖和应激的自组织进化、生物体形态发生等细胞分子生物系统原理等。     

系统遗传学与合成生物学——21世纪的生物工程产业化

基因型-表现型复杂生物系统由多基因群调控,细胞发生的信号传导路径、多基因相互作用与细胞系谱定位形成生物系统的结构-图式发生遗传学,但分子、细胞和器官的结构、图式形成机理还不很清楚。复杂生物系统的图式演化是细胞的物种进化、细胞形态发育的细胞发生非线性动力学过程,包括：1）物种基因组结构内等位基因替代构成物种内基因多样性调控;2）物种间进化的基因组结构层次级别的自组织化。系统理论应用于系统生态学（Van Dyne GM．1966）、系统生理学（Sagawa K．1973）、系统心理学（Titchener EB．1992）、系统生物医学（Kamada T．1992）、系统生物学（zieglgansherger W,Tolle TR．1993）、系统生物工程与系统遗传学（Zengg：BJ.1994）的建立,以及遗传学机理的生物系统分析。细胞的基因组结构自组织化形成生物的系统发生,基因组的结构变化形成物种的适应变异,生物体结构的基因组复制与表达的细胞自组织化构成生物个体发生。基于系统遗传学的工程应用,合成生物学探索生物系统泛进化,包括人工生物体的遗传工程、基因调控和仿生智能的纳米生物机器,构成生物系统的人工引导进化。     

人工小RNA调控元件在合成生物学中的应用北大核心CSCD

合成生物学通过改造天然系统或创造生物元件、模块和系统赋予生命体新的功能,为农业、能源、制造业及医学进步带来了巨大推动力。对元件、模块或系统的精准、定量及高效调控将对合成生命系统的控制至关重要。细菌小RNA是一类长度在50–300 bp且通常不具备翻译能力的功能小分子,在环境胁迫响应、代谢变化适应和细菌毒力控制过程中发挥着不可替代的调控作用。近年来,基于天然小RNA设计构建的人工小RNA调控元件的工作日益丰富,实现了对目的基因甚至通路的有效抑制或激活。人工小RNA分子小、灵活性高,可程序化且易于设计,几乎不会对宿主细胞造成代谢负担,因此在合成生物学中具备广泛应用前景。为促进对人工小RNA的机理理解及应用拓展,本文围绕若干人工小RNA调控元件进行了系统介绍及比较;此外,总结了其在合成生物学中的代表性应用;最后,对其未来优化方向进行了讨论。     

合成生物学在基础生命科学研究中的应用

合成生物学作为一门新兴的交叉学科,吸引了来自生物学、数理科学和工程学等不同学科的研究人员以及产业界的广泛关注和参与。它旨在通过从头创造全新的或改造已有的生物系统,实现天然生物系统不具备的功能与特性。合成生物学研究不仅具有广阔的生物产业应用前景,更为基础科研提供了全新的手段和思路。本文着眼于合成生物学―建物致知‖的理念,跟踪合成生物学研究在回答生命科学基础问题方面取得的相关成果,简述了其在细胞内分子调控网络、细胞生理学、多细胞群体形态与行为以及多物种微生态学等研究中的应用。     

复杂天然产物合成人工生物系统的设计与构建

天然产物是人类疾病预防和治疗药物的最重要来源。合成生物学技术的蓬勃发展为天然产物的开发注入了全新的活力。文中重点介绍了如何利用合成生物技术进行复杂天然产物合成人工生物系统的设计与构建,包括与此相关的生物元件理性设计、生物元件挖掘、途径装配与集成,模块的组装与系统的适配等内容。     

系统遗传学与生物技术-细胞分子生物系统的分析与合成

生物系统的科学与工程是整合系统论、实验、计算和工程方法的交叉学科研究与应用.系统生物学、系统医学,建立在系统科学和数学模型基础上,采用分子、组学生物技术和计算、生物信息技术,以及基因合成与转基因生物技术等研究生物系统原理和规律.系统遗传学与系统生物技术是研究天然与人工生物系统的基因系统与蛋白质系统构成细胞的软件信息与硬件运行系统的机理与方法.合成生物学、系统生物工程也是建立在系统科学和数学模型基础上,应用于生物系统原理设计虚拟计算机信息软件和仿生人工机器硬件、人造工程生物体和基因信息系统等.     

Computer-aided design of biological circuits using TinkerCell

Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze, and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field.     

Foundations for the design and implementation of synthetic genetic circuits

Synthetic gene circuits are designed to program new biological behaviour, dynamics and logic control. For all but the simplest synthetic phenotypes, this requires a structured approach to map the desired functionality to available molecular and cellular parts and processes. In other engineering disciplines, a formalized design process has greatly enhanced the scope and rate of success of projects. When engineering biological systems, a desired function must be achieved in a context that is incompletely known, is influenced by stochastic fluctuations and is capable of rich nonlinear interactions with the engineered circuitry. Here, we review progress in the provision and engineering of libraries of parts and devices, their composition into large systems and the emergence of a formal design process for synthetic biology.     

合成生物学及其在生物技术中的应用进展

合成生物学是一门21世纪生物学的新兴学科,它着眼生物科学与工程科学的结合,把生物系统当作工程系统"从下往上"进行处理,由"单元"(unit)到"部件"(device)再到"系统"(system)来设计,修改和组装细胞构件及生物系统.合成生物学是分子和细胞生物学、进化系统学、生物化学、信息学、数学、计算机和工程等多学科交叉的产物.目前研究应用包括两个主要方面:一是通过对现有的、天然存在的生物系统进行重新设计和改造,修改已存在的生物系统,使该系统增添新的功能.二是通过设计和构建新的生物零件、组件和系统,创造自然界中尚不存在的人工生命系统.合成生物学作为一门建立在基因组方法之上的学科,主要强调对创造人工生命形态的计算生物学与实验生物学的协同整合.必须强调的是,用来构建生命系统新结构、产生新功能所使用的组件单元既可以是基因、核酸等生物组件,也可以是化学的、机械的和物理的元件.本文跟踪合成生物学研究及应用,对其在DNA水平编程、分子修饰、代谢途径、调控网络和工业生物技术等方面的进展进行综述.     

基因组工程在医学合成生物学中的应用

合成生物学旨在建立一套完整的工程理论和方法,通过设计和组装基本生物学元件,更为有效地实现复杂生物系统的设计,并使其完成可编程的生物学功能。近年来随着可编程基因组元件的出现,特别是CRISPR和CRISPRi技术平台的建立和完善,使得合成生物学进入了一个全新发展的时期。本文重点综述CRISPR等基因组编辑和调控技术,其在构建可编程生物学元件和复杂基因线路的应用以及合成生物学在医学中(称为医学合成生物学)的发展前景。     

Applications of cell-free protein synthesis in synthetic biology: Interfacing bio-machinery with synthetic environments

Synthetic biology is built on the synthesis, engineering, and assembly of biological parts. Proteins are the first components considered for the construction of systems with designed biological functions because proteins carry out most of the biological functions and chemical reactions inside cells. Protein synthesis is considered to comprise the most basic levels of the hierarchical structure of synthetic biology. Cell-free protein synthesis has emerged as a powerful technology that can potentially transform the concept of bioprocesses. With the ability to harness the synthetic power of biology without many of the constraints of cell-based systems, cell-free protein synthesis enables the rapid creation of protein molecules from diverse sources of genetic information. Cell-free protein synthesis is virtually free from the intrinsic constraints of cell-based methods and offers greater flexibility in system design and manipulability of biological synthetic machinery. Among its potential applications, cell-free protein synthesis can be combined with various man-made devices for rapid functional analysis of genomic sequences. This review covers recent efforts to integrate cell-free protein synthesis with various reaction devices and analytical platforms.     

Toward scalable parts families for predictable design of biological circuits

Our current ability to engineer biological circuits is hindered by design cycles that are costly in terms of time and money, with constructs failing to operate as desired, or evolving away from the desired function once deployed. Synthetic biologists seek to understand biological design principles and use them to create technologies that increase the efficiency of the genetic engineering design cycle. Central to the approach is the creation of biological parts--encapsulated functions that can be composited together to create new pathways with predictable behaviors. We define five desirable characteristics of biological parts--independence, reliability, tunability, orthogonality and composability, and review studies of small natural and synthetic biological circuits that provide insights into each of these characteristics. We propose that the creation of appropriate sets of families of parts with these properties is a prerequisite for efficient, predictable engineering of new function in cells and will enable a large increase in the sophistication of genetic engineering applications.     

Practical application of synthetic biology principles

Synthetic biology can be defined as the “repurposing and redesign of biological systems for novel purposes or applications, ” and the field lies at the interface of several biological research areas. This broad definition can be taken to include a variety of investigative endeavors, and successful design of new biological paradigms requires integration of many scientific disciplines including (but not limited to) protein engineering, metabolic engineering, genomics, structural biology, chemical biology, systems biology, and bioinformatics. This review focuses on recent applications of synthetic biology principles in three areas: (i) the construction of artificial biomolecules and biomaterials; (ii) the synthesis of both fine and bulk chemicals (including biofuels); and (iii) the construction of “smart” biological systems that respond to the surrounding environment.     

Biomolecular computing systems: principles, progress and potential

The task of information processing, or computation, can be performed by natural and man-made 'devices'. Man-made computers are made from silicon chips, whereas natural 'computers', such as the brain, use cells and molecules. Computation also occurs on a much smaller scale in regulatory and signalling pathways in individual cells and even within single biomolecules. Indeed, much of what we recognize as life results from the remarkable capacity of biological building blocks to compute in highly sophisticated ways. Rational design and engineering of biological computing systems can greatly enhance our ability to study and to control biological systems. Potential applications include tissue engineering and regeneration and medical treatments. This Review introduces key concepts and discusses recent progress that has been made in biomolecular computing.     

Engineering microbes with synthetic biology frameworks

Typically, the outcome of biologically engineered unit operations cannot be controlled a priori due to the incorporation of ad hoc design into complex natural systems. To mitigate this problem, synthetic biology presents a systematic approach to standardizing biological components for the purpose of increasing their programmability and robustness when assembled with the aim to achieve novel biological functions. A complex engineered biological system using only standardized biological components is yet to exist. Nevertheless, current attempts to create and to implement modular, standardized biological components pave the way for the future creation of highly predictable artificial biological systems. Although synthetic biology frameworks can be applied to any biological engineering endeavor, this article will focus on providing a brief overview of advances in the field and its recent utilization for the engineering of microbes.     

A perspective of synthetic biology: assembling building blocks for novel functions

Synthetic biology is a recently emerging field that applies engineering formalisms to design and construct new biological parts, devices, and systems for novel functions or life forms that do not exist in nature. Synthetic biology relies on and shares tools from genetic engineering, bioengineering, systems biology and many other engineering disciplines. It is also different from these subjects, in both insights and approach. Applications of synthetic biology have great potential for novel contributions to established fields and for offering opportunities to answer fundamentally new biological questions. This article does not aim at a thorough survey of the literature and detailing progress in all different directions. Instead, it is intended to communicate a way of thinking for synthetic biology in which basic functional elements are defined and assembled into living systems or biomaterials with new properties and behaviors. Four major application areas with a common theme are discussed and a procedure (or "protocol") for a standard synthetic biology work is suggested.