Engineering and control of biological systems: A new way to tackle complex diseases

The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health.     

合成生物学与微生物遗传物质的重构

作为一门新兴学科的合成生物学已经展现出巨大的科学价值和应用前景。近年来已经发表了多篇综述文章,从不同角度对合成生物学进行了总结和论述。文章首次对合成生物学和微生物遗传学之间的关系进行了阐述,同时介绍了合成生物学在微生物遗传物质的重构方面最近的研究进展,包括微生物遗传物质的合成、设计和精简,遗传元件的标准化和遗传线路的模块化。也探讨了合成生物学与微生物遗传工程的关系。     

Models for synthetic biology

Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior.     

合成生物学与代谢工程

随着DNA重组技术的日趋成熟,代谢工程的理论和应用已经得到了迅速发展。合成生物学是近年来蓬勃发展的一门新兴学科,在许多领域都具有重要的应用。以下从改造细胞代谢的关键因子、代谢途径的调节和宿主细胞与代谢途径构建的关系等方面详细讨论了合成生物学的最新进展和合成生物学在代谢工程领域的应用。     

Engineered T cells for cancer therapy

It is now well established that the immune system can control and eliminate cancer cells. Adoptive T cell transfer has the potential to overcome the significant limitations associated with vaccine-based strategies in patients who are often immune compromised. Application of the emerging discipline of synthetic biology to cancer, which combines elements of genetic engineering and molecular biology to create new biological structures with enhanced functionalities, is the subject of this focused research review.     

合成生物学技术的研究进展——DNA合成、组装与基因组编辑

合成生物学作为一门新兴学科,其目标主要有两点:一是利用非天然的分子使其出现生命的现象,也就是―人造生命‖;二是―改造生命‖,比如利用一种生命体的元件(或经过人工改造),组装到另一个生命体中,使其产生特定功能。无论是哪种目的,对生命遗传物质DNA的操作都非常关键,其具体包括DNA的从头合成、组装和编辑等。同时,这些使能技术的进步也促进了合成生物学其他领域的发展。本文介绍了DNA操作相关的合成生物学使能技术的最新进展。     

The imminent role of protein engineering in synthetic biology

Protein engineering has for decades been a powerful tool in biotechnology for generating vast numbers of useful enzymes for industrial applications. Today, protein engineering has a crucial role in advancing the emerging field of synthetic biology, where metabolic engineering efforts alone are insufficient to maximize the full potential of synthetic biology. This article reviews the advancements in protein engineering techniques for improving biocatalytic properties to optimize engineered pathways in host systems, which are instrumental to achieve high titer production of target molecules. We also discuss the specific means by which protein engineering has improved metabolic engineering efforts and provide our assessment on its potential to continue to advance biology engineering as a whole.     

Interactive learning and action: realizing the promise of synthetic biology for global health

The emerging field of synthetic biology has the potential to improve global health. For example, synthetic biology could contribute to efforts at vaccine development in a context in which vaccines and immunization have been identified by the international community as being crucial to international development efforts and, in particular, the millennium development goals. However, past experience with innovations shows that realizing a technology’s potential can be difficult and complex. To achieve better societal embedding of synthetic biology and to make sure it reaches its potential, science and technology development should be made more inclusive and interactive. Responsible research and innovation is based on the premise that a broad range of stakeholders with different views, needs and ideas should have a voice in the technological development and deployment process. The interactive learning and action (ILA) approach has been developed as a methodology to bring societal stakeholders into a science and technology development process. This paper proposes an ILA in five phases for an international effort, with national case studies, to develop socially robust applications of synthetic biology for global health, based on the example of vaccine development. The design is based on results of a recently initiated ILA project on synthetic biology; results from other interactive initiatives described in the literature; and examples of possible applications of synthetic biology for global health that are currently being developed.     

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.     

T cell engineering as therapy for cancer and HIV: our synthetic future

It is now well established that the immune system can control and eliminate cancer cells. Adoptive T cell transfer has the potential to overcome the significant limitations associated with vaccine-based strategies in patients who are often immune compromised. Application of the emerging discipline of synthetic biology to cancer, which combines elements of genetic engineering and molecular biology to create new biological structures with enhanced functionalities, is the subject of this overview. Various chimeric antigen receptor designs, manufacturing processes and study populations, among other variables, have been tested and reported in recent clinical trials. Many questions remain in the field of engineered T cells, but the encouraging response rates pave a wide road for future investigation into fields as diverse as cancer and chronic infections.     

Restoring physiology to the undergraduate biology curriculum: a call for action

The National Research Council-sponsored report, BIO 2010: Transforming Undergraduate Education for Future Research Biologists, describes a number of significant changes that should be made to the undergraduate biology curriculum if we are to adequately train students to become the researchers of the 21st century. What should be of concern to the physiology community is the lack of identifiable physiology in the proposed revisions. This article describes the report and suggests some steps that physiologists can take to enhance our discipline in the undergraduate biology curriculum.     

The emerging age of cell-free synthetic biology

The engineering of and mastery over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology.     

Microbial synthetic biology for human therapeutics

The emerging field of synthetic biology holds tremendous potential for developing novel drugs to treat various human conditions. The current study discusses the scope of synthetic biology for human therapeutics via microbial approach. In this context, synthetic biology aims at designing, engineering and building new microbial synthetic cells that do not pre-exist in nature as well as re-engineer existing microbes for synthesis of therapeutic products. It is expected that the construction of novel microbial genetic circuitry for human therapeutics will greatly benefit from the data generated by ??omics?? approaches and multidisciplinary nature of synthetic biology. Development of novel antimicrobial drugs and vaccines by engineering microbial systems are a promising area of research in the field of synthetic biology for human theragnostics. Expression of plant based medicinal compounds in the microbial system using synthetic biology tools is another avenue dealt in the present study. Additionally, the study suggest that the traditional medicinal knowledge can do value addition for developing novel drugs in the microbial systems using synthetic biology tools. The presented work envisions the success of synthetic biology for human therapeutics via microbial approach in a holistic manner. Keeping this in view, various legal and socio-ethical concerns emerging from the use of synthetic biology via microbial approach such as patenting, biosafety and biosecurity issues have been touched upon in the later sections.     

Parts plus pipes: synthetic biology approaches to metabolic engineering

Synthetic biologists combine modular biological "parts" to create higher-order devices. Metabolic engineers construct biological "pipes" by optimizing the microbial conversion of basic substrates to desired compounds. Many scientists work at the intersection of these two philosophies, employing synthetic devices to enhance metabolic engineering efforts. These integrated approaches promise to do more than simply improve product yields; they can expand the array of products that are tractable to produce biologically. In this review, we explore the application of synthetic biology techniques to next-generation metabolic engineering challenges, as well as the emerging engineering principles for biological design.     

Teaching Synthetic Biology, Bioinformatics and Engineering to Undergraduates: The Interdisciplinary Build-a-Genome Course

A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into ~750-bp fragments. Once trained in assembly of such DNA “building blocks” by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular “lab meeting” sessions help prepare them for future roles in laboratory science.     

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.     

A Personalist Ontological Approach to Synthetic Biology

Although synthetic biology is a promising discipline, it also raises serious ethical questions that must be addressed in order to prevent unwanted consequences and to ensure that its progress leads toward the good of all. Questions arise about the role of this discipline in a possible redefinition of the concept of life and its creation. With regard to the products of synthetic biology, the moral status that they should be given as well as the ethically correct way to behave towards them are not clear. Moreover, risks that could result from a misuse of this technology or from an accidental release of synthetic organisms into the environment cannot be ignored; concerns about biosecurity and biosafety appear. Here we discuss these and other questions from a personalist ontological framework, which defends human life as an essential value and proposes a set of principles to ensure the safeguarding of this and other values that are based on it.     

Review of quantitative and qualitative studies on U.S. public perceptions of synthetic biology

How are public perceptions towards synthetic biology likely to evolve? Which factors will impact the framing of this emerging technology, its benefits and risks? The objective of this article is not to draw exhaustive conclusions about public perceptions of synthetic biology, but rather to provide readers with a review of integrated findings from the first quantitative and qualitative research ever conducted on this subject in the United States. Synthetic biology survey research shows two clear findings. The first is that most people know little or nothing about synthetic biology. Second, notwithstanding this lack of knowledge, respondents are likely to venture some remark about what they think synthetic biology is and the tradeoff between potential benefits and potential risks. Finding only some support for the “familiarity argument”—according to which support for emerging technologies will likely increase as awareness of them develops—this article suggests that analogs to cloning, genetic engineering and stem cell research appear to be recurrent in the framing process of synthetic biology. The domain of application seems to be another decisive factor in the framing of synthetic biology. Finally, acceptance of the risk-benefit tradeoff of synthetic biology seems to depend on having an oversight structure that would prove able to manage unknowns, human and environmental concerns, and long-term effects. The most important conclusion of this study is the need for additional investigation of factors that will shape public perceptions about synthetic biology, its potential benefits, and its potential risks.     

The end of "naive reductionism": rise of systems biology or renaissance of physiology?

Systems biology is an emerging discipline focused on tackling the enormous intellectual and technical challenges associated with translating genome sequence into a comprehensive understanding of how organisms are built and run. Physiology and systems biology share the goal of understanding the integrated function of complex, multicomponent biological systems ranging from interacting proteins that carry out specific tasks to whole organisms. Despite this common ground, physiology as an academic discipline runs the real risk of fading into the background and being superseded organizationally and administratively by systems biology. My goal in this article is to discuss briefly the cornerstones of modern systems biology, specifically functional genomics, nonmammalian model organisms and computational biology, and to emphasize the need to embrace them as essential components of 21st-century physiology departments and research and teaching programs.     

合成生物学中的DNA组装技术

合成生物学旨在应用工程学的研究思路及手段去设计或改造生物系统,是一个综合了科学与工程的拥有发展潜力的新兴学科,在生物医药、农业、能源、环保等方面发挥着巨大作用。DNA组装技术是合成生物学中的关键技术,也是合成生物学快速发展的限制性技术。综述了众多DNA组装技术的发展及其在合成生物学研究中的意义和应用。