Digital ‘faces’ of synthetic biology

In silicio design plays a fundamental role in the endeavour to synthesise biological systems. In particular, computer-aided design software enables users to manage the complexity of biological entities that is connected to their construction and reconfiguration. The software’s graphical user interface bridges the gap between the machine-readable data on the algorithmic subface of the computer and its human-amenable surface represented by standardised diagrammatic elements. Notations like the Systems Biology Graphical Notation (SBGN), together with interactive operations such as drag & drop, allow the user to visually design and simulate synthetic systems as ‘bio-algorithmic signs’. Finally, the digital programming process should be extended to the wet lab to manufacture the designed synthetic biological systems. By exploring the different ‘faces’ of synthetic biology, I argue that in particular computer-aided design (CAD) is pushing the idea to automatically produce de novo objects. Multifaceted software processes serve mutually aesthetic, epistemic and performative purposes by simultaneously black-boxing and bridging different data sources, experimental operations and community-wide standards. So far, synthetic biology is mainly a product of digital media technologies that structurally mimic the epistemological challenge to take both qualitative as well as quantitative aspects of biological systems into account in order to understand and produce new and functional entities.     

Cells as irreducible wholes: the failure of mechanism and the possibility of an organicist revival

According to vitalism, living organisms differ from machines and all other inanimate objects by being endowed with an indwelling immaterial directive agency, ‘vital force,’ or entelechy. While support for vitalism fell away in the late nineteenth century many biologists in the early twentieth century embraced a non vitalist philosophy variously termed organicism/holism/emergentism which aimed at replacing the actions of an immaterial spirit with what was seen as an equivalent but perfectly natural agency—the emergent autonomous activity of the whole organism. Organicists hold that organisms unlike machines are ‘more than the sum of their parts’ and predict that the vital properties of living things can never be explained in terms of mechanical analogies and that the reductionist agenda is doomed to failure. Here we review the current status of the mechanist and organicist conceptions of life particularly as they apply to the cell. We argue that despite the advances in biological knowledge over the past six decades since the molecular biological revolution, especially in the fields of genetics and cell biology the unique properties of living cells have still not been simulated in mechanical systems nor yielded to reductionist—analytical explanations. And we conclude that despite the dominance of the mechanistic–reductionist paradigm through most of the past century the possibility of a twentyfirst century organicist revival cannot be easily discounted.     

Queueing up for enzymatic processing: correlated signaling through coupled degradation

High‐throughput technologies have led to the generation of complex wiring diagrams as a post‐sequencing paradigm for depicting the interactions between vast and diverse cellular species. While these diagrams are useful for analyzing biological systems on a large scale, a detailed understanding of the molecular mechanisms that underlie the observed network connections is critical for the further development of systems and synthetic biology. Here, we use queueing theory to investigate how ‘waiting lines’ can lead to correlations between protein ‘customers’ that are coupled solely through a downstream set of enzymatic ‘servers’. Using the E. coli ClpXP degradation machine as a model processing system, we observe significant cross‐talk between two networks that are indirectly coupled through a common set of processors. We further illustrate the implications of enzymatic queueing using a synthetic biology application, in which two independent synthetic networks demonstrate synchronized behavior when common ClpXP machinery is overburdened. Our results demonstrate that such post‐translational processes can lead to dynamic connections in cellular networks and may provide a mechanistic understanding of existing but currently inexplicable links.     

Knowledge-making distinctions in synthetic biology

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems.     

Two sides of the same coin? The (techno)epistemic cultures of systems and synthetic biology

Systems and synthetic biology both emerged around the turn of this century as labels for new research approaches. Although their disciplinary status as well as their relation to each other is rarely discussed in depth, now and again the idea is invoked that both approaches represent ‘two sides of the same coin’. The following paper focuses on this general notion and compares it with empirical findings concerning the epistemic cultures prevalent in the two contexts. Drawing on interviews with researchers from both fields, on participatory observation in conferences and courses and on documentary analysis, this paper delineates differences and similarities, incompatibilities and blurred boundaries. By reconstructing systems and synthetic biology’s epistemic cultures, this paper argues that they represent two ‘communities of vision’, encompassing heterogeneous practices. Understanding the relation of the respective visions of understanding nature and engineering life is seen as indispensible for the characterisation of (techno)science in more general terms. Depending on the conceptualisation of understanding and construction (or: science and engineering), related practices such as in silico modelling for enhancing understanding or enabling engineering can either be seen as incommensurable or ‘two sides of one coin’.     

A “Living” Machine

Biomimetics (or bionics) is the engineering discipline that constructs artificial systems using biological principles. The ideal final result in biomimetics is to create a living machine. But what are the desirable and non-desirable properties of biomimetic product7 Where can natural prototypes be found7 How can technical solutions be transferred from nature to technology? Can we use living nature like LEC, O bricks for oonstmction our machines? How can biology help us? What is a living machine? In biomimetic practice only some “part“ (organ, part of organ, tissue) of the observed whole organism is utilized. A possible template for future super-organism extension for biornimetic methods might be drawn from experiments in holistic ecological agriculture (ecological design, permacuhure, ecological engineering, etc. ). The necessary translation of these roles to practical action can be achieved with the Russian Theory of Inventive Problem Solving (TRIZ), specifically adjusted to biology. Thus, permaculture, reinforced by a TRIZ conceptual framework, might provide the basis for Super-Organismic Bionics, which is hypothesized as necessary for effective ecological engineering. This hypothesis is supported by a case study-the design of a sustainable artificial nature reserve for wild pollinators as a living machine.     

Synthetic circuits,devices and modules

The aim of synthetic biology is to design artificial biological systems for novel applications. From an engineering perspective, construction of biological systems of defined functionality in a hierarchical way is fundamental to this emerging field. Here, we highlight some current advances on design of several basic building blocks in synthetic biology including the artificial gene control elements, synthetic circuits and their assemblies into devices and modules. Such engineered basic building blocks largely expand the synthetic toolbox and contribute to our understanding of the underlying design principles of living cells.     

A day of systems and synthetic biology for non‐experts

From understanding ageing to the creation of artificial membrane‐bounded ‘organisms’, systems biology and synthetic biology are seen as the latest revolutions in the life sciences. They certainly represent a major change of gear, but paradigm shifts? This is open to debate, to say the least. For scientists they open up exciting ways of studying living systems, of formulating the ‘laws of life’, and the relationship between the origin of life, evolution and artificial biological systems. However, the ethical and societal considerations are probably indistinguishable from those of human genetics and genetically modified organisms. There are some tangible developments just around the corner for society, and as ever, our ability to understand the consequences of, and manage, our own progress lags far behind our technological abilities. Furthermore our educational systems are doing a bad job of preparing the next generation of scientists and non‐scientists.     

Synthetic biology between technoscience and thing knowledge

Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called ‘thing knowledge’. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world—knowledge that, in turn, can be accessed via continuous experimental interrogation.     

Scientific perspectivism: A philosopher of science's response to the challenge of big data biology

Big data biology—bioinformatics, computational biology, systems biology (including ‘omics’), and synthetic biology—raises a number of issues for the philosophy of science. This article deals with several such: Is data-intensive biology a new kind of science, presumably post-reductionistic? To what extent is big data biology data-driven? Can data ‘speak for themselves?’ I discuss these issues by way of a reflection on Carl Woese’s worry that “a society that permits biology to become an engineering discipline, that allows that science to slip into the role of changing the living world without trying to understand it, is a danger to itself.” And I argue that scientific perspectivism, a philosophical stance represented prominently by Giere, Van Fraassen, and Wimsatt, according to which science cannot as a matter of principle transcend our human perspective, provides the best resources currently at our disposal to tackle many of the philosophical issues implied in the modeling of complex, multilevel/multiscale phenomena.     

Structural and organisational conditions for being a machine

Although the analogy between macroscopic machines and biological molecular devices plays an important role in the conceptual framework of both neo-mechanistic accounts and nanotechnology, it has recently been claimed that certain complex molecular devices (consisting of biological or synthetic macromolecular aggregates) cannot be considered machines since they are subject to physicochemical forces that are different from those of macroscopic machines. However, the structural and physicochemical conditions that allow both macroscopic machines and microscopic devices to work and perform new functions, through a combination of elemental functional parts, have not yet been examined. In order to fill this void, this paper has a threefold aim: first, to clarify the structural and organisational conditions of macroscopic machines and microscopic devices; second, to determine whether the machine-like analogy fits nanoscale devices; and third, to assess whether the machine-like analogy is appropriate for describing the behaviour of some biological macromolecules. Finally, the paper gives an account of ‘machine’ which, while acknowledging the physicochemical and organisational differences between man-made machines and biological microscopic devices, nevertheless identifies a common conceptual core that allows us to consider the latter ‘machines’.     

Synthetic biology advancing clinical applications

The 'omics' era, with its identification of genetic and protein components, has combined with systems biology, which provided insights into network structures, to set the stage for synthetic biology, an emerging interdisciplinary life science that uses engineering principles. By capitalizing on an iterative design cycle that involves molecular and computational biology tools to assemble functional designer devices from a comprehensive catalogue of standardized biological components with predictable functions, synthetic biology has significantly advanced our understanding of complex control dynamics that program living systems. Such insights, collected over the past decade, are priming a variety of synthetic biology-inspired biomedical applications that have the potential to revolutionize drug discovery and production technologies, as well as treatment strategies for infectious diseases and metabolic disorders.     

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.     

Designer Condensates: A Toolkit for the Biomolecular Architect

Protein phase separation has emerged as a novel paradigm to explain the biogenesis of membraneless organelles and other so-called biomolecular condensates. While the implication of this physical phenomenon within cell biology is providing us with novel ways for understanding how cells compartmentalize biochemical reactions and encode function in such liquid-like assemblies, the newfound appreciation of this process also provides immense opportunities for designing and sculpting biological matter. Here, we propose that understanding the cell’s instruction manual of phase separation will enable bioengineers to begin creating novel functionalized biological materials and unprecedented tools for synthetic biology. We present FASE as the synthesis of the existing sticker-spacer framework, which explains the physical driving forces underlying phase separation, with quintessential principles of Scandinavian design. FASE serves both as a designer condensates catalogue and construction manual for the aspiring (membraneless) biomolecular architect. Our approach aims to inspire a new generation of bioengineers to rethink phase separation as an opportunity for creating reactive biomaterials with unconventional properties and to encode novel biological function in living systems. Although still in its infancy, several studies highlight how designer condensates have immediate and widespread potential applications in industry and medicine.     

More on how and why: cause and effect in biology revisited

In 1961, Ernst Mayr published a highly influential article on the nature of causation in biology, in which he distinguished between proximate and ultimate causes. Mayr argued that proximate causes (e.g. physiological factors) and ultimate causes (e.g. natural selection) addressed distinct ‘how’ and ‘why’ questions and were not competing alternatives. That distinction retains explanatory value today. However, the adoption of Mayr’s heuristic led to the widespread belief that ontogenetic processes are irrelevant to evolutionary questions, a belief that has (1) hindered progress within evolutionary biology, (2) forged divisions between evolutionary biology and adjacent disciplines and (3) obstructed several contemporary debates in biology. Here we expand on our earlier (Laland et al. in Science 334:1512–1516, 2011) argument that Mayr’s dichotomous formulation has now run its useful course, and that evolutionary biology would be better served by a concept of reciprocal causation, in which causation is perceived to cycle through biological systems recursively. We further suggest that a newer evolutionary synthesis is unlikely to emerge without this change in thinking about causation.     

On the road to synthetic life: the minimal cell and genome-scale engineering

Synthetic biology employs rational engineering principles to build biological systems from the libraries of standard, well characterized biological parts. Biological systems designed and built by synthetic biologists fulfill a plethora of useful purposes, ranging from better healthcare and energy production to biomanufacturing. Recent advancements in the synthesis, assembly and “booting-up” of synthetic genomes and in low and high-throughput genome engineering have paved the way for engineering on the genome-wide scale. One of the key goals of genome engineering is the construction of minimal genomes consisting solely of essential genes (genes indispensable for survival of living organisms). Besides serving as a toolbox to understand the universal principles of life, the cell encoded by minimal genome could be used to build a stringently controlled “cell factory” with a desired phenotype. This review provides an update on recent advances in the genome-scale engineering with particular emphasis on the engineering of minimal genomes. Furthermore, it presents an ongoing discussion to the scientific community for better suitability of minimal or robust cells for industrial 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.     

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.