Systems biology in animal sciences

Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed 'omics' technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A 'system' approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with 'system approaches' in animal sciences, providing exciting opportunities to predict and modulate animal traits.     

传统中国医药与现代系统生物学研究理论的殊途同归

系统生物学是研究一个生物系统中所有组成成分(基因、mRNA、蛋白质等)的构成与组分之间相互关系的学科,近年来,系统生物学作为后基因组学时代研究的一个重要内容,已广泛深入到生命科学和医药学的各个领域。而作为中国传统医学而言,似乎与之相去甚远,然而当我们对这两个新老学科基础理论进行比较时,我们发现:传统中国医药与现代系统生物学研究理论的殊途同归。有鉴于此,本文论述了系统生物学和中医学的思想起源、相互联系,基于系统生物学的发展、研究思路和方法,阐述了生物学由还原论的研究方法过渡到系统论的研究方法,强调对生命现象从系统和整体的层次进行研究和把握,对传统中医学研究方法的变革起到了推动作用,最后对系统生物学在中医药学未来发展进行了评价。     

Ins and Outs of Systems Biology vis-à-vis Molecular Biology: Continuation or Clear Cut?

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology and ‘transcends’ its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement.     

Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine

The emergence of systems biology is bringing forth a new set of challenges for advancing science and technology. Defining ways of studying biological systems on a global level, integrating large and disparate data types, and dealing with the infrastructural changes necessary to carry out systems biology, are just a few of the extraordinary tasks of this growing discipline. Despite these challenges, the impact of systems biology will be far-reaching, and significant progress has already been made. Moving forward, the issue of how to use systems biology to improve the health of individuals must be a priority. It is becoming increasingly apparent that the field of systems biology and one of its important disciplines, proteomics, will have a major role in creating a predictive, preventative, and personalized approach to medicine. In this review, we define systems biology, discuss the current capabilities of proteomics and highlight some of the necessary milestones for moving systems biology and proteomics into mainstream health care.     

Designing de novo: interdisciplinary debates in synthetic biology

Synthetic biology is often presented as a promissory field that ambitions to produce novelty by design. The ultimate promise is the production of living systems that will perform new and desired functions in predictable ways. Nevertheless, realizing promises of novelty has not proven to be a straightforward endeavour. This paper provides an overview of, and explores the existing debates on, the possibility of designing living systems de novo as they appear in interdisciplinary talks between engineering and biological views within the field of synthetic biology. To broaden such interdisciplinary debates, we include the views from the social sciences and the humanities and we point to some fundamental sources of disagreement within the field. Different views co-exist, sometimes as controversial tensions, but sometimes also pointing to integration in the form of intermediate positions. As the field is emerging, multiple choices are possible. They will inform alternative trajectories in synthetic biology and will certainly shape its future. What direction is best is to be decided in reflexive and socially robust ways.     

计算系统生物学:理论、方法及在药物研发中的应用

计算系统生物学是一个多学科交叉的新兴领域,旨在通过整合海量数据建立其生物系统相互作用的复杂网络。数据的整合和模型的建立需要发展合适的数学方法和软件工具,这也是计算系统生物学的主要任务。生物系统模型有助于从整体上理解生物体的内在功能和特性。同时,生物网络模型在药物研发中的应用也越来越受到制药企业以及新药研发机构的重视,如用于特异性药物作用靶点的预测和药物毒性评估等。该文简要介绍计算系统生物学的常见网络和计算模型,以及建立模型所用的研究方法,并阐述其在建模和分析中的作用及面临的问题和挑战。     

Applying modelling experiences from the past to shape crop systems biology: the need to converge crop physiology and functional genomics

Functional genomics has been driven greatly by emerging experimental technologies. Its development as a scientific discipline will be enhanced by systems biology, which generates novel, quantitative hypotheses via modelling. However, in order to better assist crop improvement, the impact of developing functional genomics needs to be assessed at the crop level, given a projected diminishing effect of genetic alteration on phenotypes from the molecule to crop levels. This review illustrates a recently proposed research field, crop systems biology, which is located at the crossroads of crop physiology and functional genomics, and intends to promote communications between the two. Past experiences with modelling whole-crop physiology indicate that the layered structure of biological systems should be taken into account. Moreover, modelling not only plays a role in data synthesis and quantitative prediction, but certainly also in heuristics and system design. These roles of modelling can be applied to crop systems biology to enhance its contribution to our understanding of complex crop phenotypes and subsequently to crop improvement. The success of crop systems biology needs commitments from scientists along the entire knowledge chain of plant biology, from molecule or gene to crop and agro-ecosystem.     

Calculating life? Duelling discourses in interdisciplinary systems biology

A high profile context in which physics and biology meet today is in the new field of systems biology. Systems biology is a fascinating subject for sociological investigation because the demands of interdisciplinary collaboration have brought epistemological issues and debates front and centre in discussions amongst systems biologists in conference settings, in publications, and in laboratory coffee rooms. One could argue that systems biologists are conducting their own philosophy of science. This paper explores the epistemic aspirations of the field by drawing on interviews with scientists working in systems biology, attendance at systems biology conferences and workshops, and visits to systems biology laboratories. It examines the discourses of systems biologists, looking at how they position their work in relation to previous types of biological inquiry, particularly molecular biology. For example, they raise the issue of reductionism to distinguish systems biology from molecular biology. This comparison with molecular biology leads to discussions about the goals and aspirations of systems biology, including epistemic commitments to quantification, rigor and predictability. Some systems biologists aspire to make biology more similar to physics and engineering by making living systems calculable, modelable and ultimately predictable-a research programme that is perhaps taken to its most extreme form in systems biology's sister discipline: synthetic biology. Other systems biologists, however, do not think that the standards of the physical sciences are the standards by which we should measure the achievements of systems biology, and doubt whether such standards will ever be applicable to 'dirty, unruly living systems'. This paper explores these epistemic tensions and reflects on their sociological dimensions and their consequences for future work in the life sciences.     

Towards a systems level analysis of health and nutrition

Although theoretical systems analysis has been available for over half a century, the recent advent of omic high-throughput analytical platforms along with the integration of individual tools and technologies has given rise to the field of modern systems biology. Coupled with information technology, bioinformatics, knowledge management and powerful mathematical models, systems biology has opened up new vistas in our understanding of complex biological systems. Currently there are two distinct approaches that include the inductively driven computational systems biology (bottom-up approach) and the deductive data-driven top-down analysis. Such approaches offer enormous potential in the elucidation of disease as well as defining key pathways and networks involved in optimal human health and nutrition. The tools and technologies now available in systems biology analyses offer exciting opportunities to develop the emerging areas of personalized medicine and individual nutritional profiling.     

系统生物学——生命科学的新领域

系统生物学是继基因组学、蛋白质组学之后一门新兴的生物学交叉学科,代表21世纪生物学的未来.最近,系统生物学研究机构纷纷成立.在研究上,了解一个复杂的生物系统需要整合实验和计算方法.基因组学和蛋白质组学中的高通量方法为系统生物学发展提供了大量的数据.计算生物学通过数据处理、模型构建和理论分析,成为系统生物学发展的一个必不可缺、强有力的工具.在应用上,系统生物学代表新一代医药开发和疾病防治的方向.     

Opportunities for yeast metabolic engineering: Lessons from synthetic biology

Constant progress in genetic engineering has given rise to a number of promising areas of research that facilitated the expansion of industrial biotechnology. The field of metabolic engineering, which utilizes genetic tools to manipulate microbial metabolism to enhance the production of compounds of interest, has had a particularly strong impact by providing new platforms for chemical production. Recent developments in synthetic biology promise to expand the metabolic engineering toolbox further by creating novel biological components for pathway design. The present review addresses some of the recent advances in synthetic biology and how these have the potential to affect metabolic engineering in the yeast Saccharomyces cerevisiae. While S. cerevisiae for years has been a robust industrial organism and the target of multiple metabolic engineering trials, its potential for synthetic biology has remained relatively unexplored and further research in this field could strongly contribute to industrial biotechnology. This review also addresses are general considerations for pathway design, ranging from individual components to regulatory systems, overall pathway considerations and whole-organism engineering, with an emphasis on potential contributions of synthetic biology to these areas. Some examples of applications for yeast synthetic biology and metabolic engineering are also discussed.     

Directed evolution: an evolving and enabling synthetic biology tool

Synthetic biology, with its goal of designing biological entities for wide-ranging purposes, remains a field of intensive research interest. However, the vast complexity of biological systems has heretofore rendered rational design prohibitively difficult. As a result, directed evolution remains a valuable tool for synthetic biology, enabling the identification of desired functionalities from large libraries of variants. This review highlights the most recent advances in the use of directed evolution in synthetic biology, focusing on new techniques and applications at the pathway and genome scale.     

Mass spectrometry-based proteomics for systems biology

Mass spectrometry (MS)-based proteomics has significantly contributed to the development of systems biology, a new paradigm for the life sciences in which biological processes are addressed in terms of dynamic networks of interacting molecules. Because of its advanced analytical capabilities, MS-based proteomics has been used extensively to identify the components of biological systems, and it is the method of choice to consistently quantify the effects of network perturbation in time and space. Herein, we review recent contributions of MS to systems biology and discuss several examples that illustrate the importance of mass spectrometry to elucidate the components and interactions of molecular networks.     

系统生物学(Systems Biology)的几大重要问题

近几年来,系统生物学从正式提出到受到普遍关注和研究,对生物学的研究发展起了革命性的变化。主要从系统生物学的发展及其内容进行分析,讨论了生物数据整合,模型建立和模拟分析等几点关键性的问题,并展望了系统生物学的研究。     

Synthetic biology through biomolecular design and engineering

Synthetic biology is a rapidly growing field that has emerged in a global, multidisciplinary effort among biologists, chemists, engineers, physicists, and mathematicians. Broadly, the field has two complementary goals: To improve understanding of biological systems through mimicry and to produce bio-orthogonal systems with new functions. Here we review the area specifically with reference to the concept of synthetic biology space, that is, a hierarchy of components for, and approaches to generating new synthetic and functional systems to test, advance, and apply our understanding of biological systems. In keeping with this issue of Current Opinion in Structural Biology, we focus largely on the design and engineering of biomolecule-based components and systems.     

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.     

Opportunities in the design and application of RNA for gene expression control

The past decade of synthetic biology research has witnessed numerous advances in the development of tools and frameworks for the design and characterization of biological systems. Researchers have focused on the use of RNA for gene expression control due to its versatility in sensing molecular ligands and the relative ease by which RNA can be modeled and designed compared to proteins. We review the recent progress in the field with respect to RNA-based genetic devices that are controlled through small molecule and protein interactions. We discuss new approaches for generating and characterizing these devices and their underlying components. We also highlight immediate challenges, future directions and recent applications of synthetic RNA devices in engineered biological systems.