On microRNA and the need for exploratory experimentation in post-genomic molecular biology

This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion.     

Metabolic modeling of microbial strains in silico

The large volume of genome-scale data that is being produced and made available in databases on the World Wide Web is demanding the development of integrated mathematical models of cellular processes. The analysis of reconstructed metabolic networks as systems leads to the development of an in silico or computer representation of collections of cellular metabolic constituents, their interactions and their integrated function as a whole. The use of quantitative analysis methods to generate testable hypotheses and drive experimentation at a whole-genome level signals the advent of a systemic modeling approach to cellular and molecular biology.     

Exploratory experimentation and scientific practice: metagenomics and the proteorhodopsin case

Exploratory experimentation and high-throughput molecular biology appear to have considerable affinity for each other. Included in the latter category is metagenomics, which is the DNA-based study of diverse microbial communities from a vast range of non-laboratory environments. Metagenomics has already made numerous discoveries and these have led to reinterpretations of fundamental concepts of microbial organization, evolution, and ecology. The most outstanding success story of metagenomics to date involves the discovery of a rhodopsin gene, named proteorhodopsin, in marine bacteria that were never suspected to have any photobiological capacities. A discussion of this finding and its detailed investigation illuminates the relationship between exploratory experimentation and metagenomics. Specifically, the proteorhodopsin story indicates that a dichotomous interpretation of theory-driven and exploratory experimentation is insufficient and that an interactive understanding of these two types of experimentation can be usefully supplemented by another category, "natural history experimentation". Further reflection on the context of metagenomics suggests the necessity of thinking more historically about exploratory and other forms of experimentation.     

From philosophy to science (to natural philosophy): evolutionary developmental perspectives

This paper focuses on abstraction as a mode of reasoning that facilitates a productive relationship between philosophy and science. Using examples from evolutionary developmental biology, I argue that there are two areas where abstraction can be relevant to science: reasoning explication and problem clarification. The value of abstraction is characterized in terms of methodology (modeling or data gathering) and epistemology (explanatory evaluation or data interpretation).     

Trends in computational biology: a summary based on a RECOMB plenary lecture, 1999.

Computational biology, a term coined from analogy to the role of computing in the physical sciences, is now coming into its own as a major element of contemporary biological and biomedical research. Information science and computational science provide essential tools for next generation biological science efforts, from focusing the direction of experimental studies to providing knowledge and insight that can not otherwise be obtained. Going beyond the revolution in biology reflected in the successes of the genome project and driven by the power of molecular biology techniques, computational approaches will provide an underpinning for the integration of broad disciplines for development of a quantitative systems approach to understanding the mechanisms in the life of the cell.     

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.     

展望21世纪的生命科学

对本世纪以来发展迅猛异常的生物科学的概况,特别是近对二三十年来,在分子生物学的带动下,生命科学在结构分子生物学;中心法则及其后的生物学细节研究;基因表达、调控和发育生物学;基因组计划和应用生物学及生物技术的发展;宏观生物学等方面讨论了生命科学的发展和特点,并从四个主要方面对２１世纪生命科学（包括生物技术）的发展趋势进行了预测,以达到综览生命科学全局,明确今后发展方向的目的。     

Systems biology,emergence and antireductionism

This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed.Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist–antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported.     

Microfluidics-based systems biology

Systems biology seeks to develop a complete understanding of cellular mechanisms by studying the functions of intra- and inter-cellular molecular interactions that trigger and coordinate cellular events. However, the complexity of biological systems causes accurate and precise systems biology experimentation to be a difficult task. Most biological experimentation focuses on highly detailed investigation of a single signaling mechanism, which lacks the throughput necessary to reconstruct the entirety of the biological system, while high-throughput testing often lacks the fidelity and detail necessary to fully comprehend the mechanisms of signal propagation. Systems biology experimentation, however, can benefit greatly from the progress in the development of microfluidic devices. Microfluidics provides the opportunity to study cells effectively on both a single- and multi-cellular level with high-resolution and localized application of experimental conditions with biomimetic physiological conditions. Additionally, the ability to massively array devices on a chip opens the door for high-throughput, high fidelity experimentation to aid in accurate and precise unraveling of the intertwined signaling systems that compose the inner workings of the cell.     

系统生物学对医学的影响

系统生物学是21世纪最前沿的科学之一,它是随着生命科学飞速发展而产生的一门新兴生物学分支[1],它综合数学、信息科学和生物学的各种工具来阐明和理解大量的数据所包含的生物医学意义,从而使人们能够从整体上理解生物医学系统并精确、量化地预测生物医学系统的行为。随着系统生物学的发展及其理论的突破,将在疾病诊治、新药开发、预防医学方面发挥重要的作用,有助于弥补传统医学缺陷并促进其发展。     

Live cell imaging using wide-field microscopy and deconvolution

The use of fluorescence imaging methods, most recently based on fluorescent protein technology, and the availability of high quality fluorescence imaging systems have driven a revolution in cell and molecular biology. Live cell imaging, especially using fluorescence, is now used in a wide variety of assays in academic and commercial laboratories. The use of this technology requires particular attention to be paid to cell engineering, the design of the image acquisition system, the imaging protocol, and subsequent processing and analytic methods. In this review, we discuss each of these steps, highlighting practical techniques developed by us and others.     

The Barcode of Life Data Portal: bridging the biodiversity informatics divide for DNA barcoding

With the volume of molecular sequence data that is systematically being generated globally, there is a need for centralized resources for data exploration and analytics. DNA Barcode initiatives are on track to generate a compendium of molecular sequence-based signatures for identifying animals and plants. To date, the range of available data exploration and analytic tools to explore these data have only been available in a boutique form--often representing a frustrating hurdle for many researchers that may not necessarily have resources to install or implement algorithms described by the analytic community. The Barcode of Life Data Portal (BDP) is a first step towards integrating the latest biodiversity informatics innovations with molecular sequence data from DNA barcoding. Through establishment of community driven standards, based on discussion with the Data Analysis Working Group (DAWG) of the Consortium for the Barcode of Life (CBOL), the BDP provides an infrastructure for incorporation of existing and next-generation DNA barcode analytic applications in an open forum.     

Biochemical individuality reflected in chromatographic, electrophoretic and mass-spectrometric profiles

This review discusses the current trends in molecular profiling for the emerging systems biology applications. Historically, the methodological developments in separation science were coincident with the availability of new ionization techniques in mass spectrometry. Coupling miniaturized separation techniques with technologically-advanced MS instrumentation and the modern data processing capabilities are at the heart of current platforms for proteomics, glycomics and metabolomics. These are being featured here by the examples from quantitative proteomics, glycan mapping and metabolomic profiling of physiological fluids.     

Taking the Relational Turn: Biosemiotics and Some New Trends in Biology

A cluster of similar trends emerging in separate fields of science and philosophy points to new opportunities to apply biosemiotic ideas as tools for conceptual integration in theoretical biology. I characterize these developments as the outcome of a “relational turn” in these disciplines. They signal a shift of attention away from objects and things and towards relational structures and processes. Increasingly sophisticated research technologies of molecular biology have generated an enormous quantity of experimental data, sparking a need for relational approaches that could help to find recurrent patterns in the mass of data. Earlier conceptions of relational biology and cybernetics, once deemed too abstract and speculative, are now resurrected and applied by means of new computational and simulation tools. I think this receptivity should be extended to incorporate nets of semiotic relations as heuristic guides for discerning global patterns of interactions in living systems. In this article I review aspects of systems biology and new directions in evolutionary theory, focusing on the role of circular and downward causation in relational structures and dynamical networks. I also indicate promising avenues of integration of some ideas of biosemiotics with those emerging from these new currents in biology. Relational developments in biology bear a telling similarity to a parallel relational turn presently manifest in the philosophy of science, rooted in the philosophy of physics and mathematics and in different varieties of structural and informational realism. The recognition of the relational nature of reality within these disciplines entails a tacit repudiation of nominalistic biases in science that have hindered the reception of semitiotic conceptions in biology. In previous investigations I explored connections between two kinds of relational structures: the networks of self-referential circular loops that appear pervasively in living systems, and the triadic relational structures that Peircean semiotics places at the basis of all semiotic transactions. Current relational views in the sciences seem oblivious to the difference between dyadic and triadic relations. Incorporating this essential distinction from biosemiotics into other fields could be a first step in seizing the opportunities opened by the relational turn for a renewal of biology and of natural philosophy in general, across disciplinary boundaries.     

构建基于磁珠微流控芯片的iFlora遗传信息高效获取系统

磁珠以其比表面积大、易与生物分子耦联、操控方便等优点,在生命科学中得到了广泛应用。随着微机电系统（MicroElectroMechanicalSystems,MEMS）技术的发展,将磁珠应用到微流控芯片中构建磁珠微流控分析系统,为生物样品分离、检测提供了一种全新方法。新一代植物志iFlora融入现代DNA测序技术．应用高速发展的信息、网络技术及云计算分析平台,收集、整合和管理植物物种相关信息,以实现物种智能鉴定和数据提取,而包括DNA条形码在内的遗传信息及其获取技术在iFlora中的作用至关重要。本文重点概述了基于纳米磁珠的微流控芯片技术及其在分子生物学领域中的应用,提出构建基于纳米磁珠微流控芯片的iFlora遗传信息采集系统,在微芯片上完成从DNA提取到测序全过程,实现物种遗传信息的快速、高效获取。     

Interview with Sydney Brenner

The following text is an edited version of a recent interview with Sydney Brenner who has been at the forefront of many developments in molecular biology since the 1950s. It provides a participant’s view on current issues in the history and epistemology of molecular biology. The main issue raised by Brenner regards the relation of molecular biology to the new field of systems biology. Brenner defends the original programme of molecular biology—the molecular explanation of living processes—that in his view has yet to be completed. The programme of systems biology in contrast he views as either trivial or as not achievable since it purports to deal with inverse problems that are impossible to solve in complex living systems. Other issues covered in the conversation concern the impact of the human genome sequencing project, the commercial turn in molecular biology and the contested disciplinary status of the science.     

Is There Enough Science for Conservation Action?

We argue that there is not enough science to appropriately support many of the conservation measures currently being proposed, and hence, we cannot be sure of the objectivity of the conservation actions being implemented. The objectivity claimed to be underlying conservation actions is more assumed than real. We also suggest that the approach to conservation is driven more by moral commitments than by tested concepts, and it is further biased by our anthropocentric evaluation of ecological processes and their outcomes. Conservation science is a young subject, which needs to be nourished while it continues to feed on its roots-ecology and evolutionary biology.     

Reverse engineering the embryo: a graduate course in developmental biology for engineering students at the University of Manitoba,Canada

Our desire to educate engineers to be able to understand the component processes of embryogenesis, is driven by the notion that only when principles borrowed from mathematics, fluid mechanics, materials science, etc. are applied to classical problems in developmental biology, will sufficient comprehension be achieved to permit successful understanding and therapeutic manipulation of embryos. As it now stands, biologists seldom possess either skills or interest in those areas of endeavor. Thus, we have determined that it is easier to educate engineers in the principles of developmental biology than to help biologists deal with the complexities of engineering. We describe a graduate course that has been taken, between 1999 and 2002, by 17 engineering students. Our goal is to prepare them to reverse engineer the embryo, i.e., to look at it as an object or process whose construction, albeit self-construction, might be explicable in terms of engineering principles applied at molecular, cellular and whole embryo levels.