Metabolic systems biology

The first full genome sequences were established in the mid-1990s. Shortly thereafter, genome-scale metabolic network reconstructions appeared. Since that time, we have witnessed an exponential growth in their number and uses. Here I discuss, from a personal point of view, four topics: (1) the placement of metabolic systems biology in the context of broader scientific developments, (2) its foundational concepts, (3) some of its current uses, and (4) some of the expected future developments in the field.     

Maps, books and other metaphors for systems biology

We briefly review the use of metaphors in science and progressively focus on fields from biology and molecular biology to genomics and bioinformatics. We discuss how metaphors are both a tool for scientific exploration and a medium for public communication of complex subjects, by various short examples. Finally, we propose a metaphor for systems biology that provides an illuminating perspective for the ambitious goals of this field and delimits its current agenda.     

系统生物学和合成生物学研究在生物燃料生产菌株改造中的应用

基于生物质资源生产环境友好的生物燃料,对经济和社会的可持续发展具有重要意义,但其生产成本高的问题十分突出,而高效生产菌株的获得是解决这一问题的根本出路。以下综述了利用系统生物学研究所获得的信息进行菌种改造的过程,重点论述了生产菌株胁迫耐受性方面的研究进展,并讨论了系统生物学、合成生物学和代谢工程技术在改造生物燃料生产菌株中的应用,展望了合成生物学在构建高效生物能源生产菌株方面应用的前景。     

Vaccinology in the era of high-throughput biology

Vaccination has been tremendously successful saving lives and preventing infections. However, the development of vaccines against global pandemics such as HIV, malaria and tuberculosis has been obstructed by several challenges. A major challenge is the lack of knowledge about the correlates and mechanisms of protective immunity. Recent advances in the application of systems biological approaches to analyse immune responses to vaccination in humans are beginning to yield new insights about mechanisms of vaccine immunity, and to define molecular signatures, induced rapidly after vaccination, that correlate with and predict vaccine induced immunity. Here, we review these advances and discuss the potential of this systems vaccinology approach in defining novel correlates of protection in clinical trials, and in infection-induced ‘experimental challenge models'' in humans.     

合成生物学

近年来用化学合成的手段合成生物物质的研究进展很快。有感染活力的小儿麻痹症病毒RNA与φX-174噬菌体基因先后合成成功。估计2006年可能会有能合成1百万bp DNA的仪器问世。此外,目前已能向蛋白质中引入80种非常见氨基酸,从而使蛋白质获得新的性质。化学合成的进展使合成与改造生命成为现实,这对研究生物学基本规律有很大的意义,但这也是一把“双刃剑”,带来伦理与反恐的问题及对可能的潜在威胁的担忧。2004年6月在美国麻省理工学院举行了第一届合成生物学国际会议。2005年8月在美国旧金山举行的合成生物学会议,讨论了生物合成这个领域对药物发展、细胞重编程、生物机器人等方面的潜在意义。     

New tools and new biology: Recent miniaturized systems for molecular and cellular biology

Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology.     

Building momentum for systems and synthetic biology in India

Biological systems are inherently noisy. Predicting the outcome of a perturbation is extremely challenging. Traditional reductionist approach of describing properties of parts, vis-a-vis higher level behaviour has led to enormous understanding of fundamental molecular level biology. This approach typically consists of converting genes into junk (knock-down) and garbage (knock-out) and observe how a system responds. To enable broader understanding of biological dynamics, an integrated computational and experimental strategy was formally proposed in mid 1990s leading to the re-emergence of Systems Biology. However, soon it became clear that natural systems were far more complex than expected. A new strategy to address biological complexity was proposed at MIT (Massachusetts Institute of Technology) in June 2004, when the first meeting of synthetic biology was held. Though the term ‘synthetic biology’ was proposed during 1970s (Szybalski in Control of gene expression, Plenum Press, New York, 1974), the usage of the original concept found an experimental proof in 2000 with the demonstration of a three-gene circuit called repressilator (Elowitz and Leibler in Nature, 403:335–338, 2000). This encouraged people to think of forward engineering biology from a set of well described parts.     

Whither systems biology

Cell biologists are interested in how complexity arises from the interaction of different molecules. However, cells are many orders of magnitude larger than the protein-binding interfaces. To bridge these vast difference in scales, biologists construct hierarchies of organization of cellular structures. I describe how systems biology provides an approach to bridge these different scales.     

Improved understanding of gene expression regulation using systems biology

This article reviews the current state of systems biology approaches, including the experimental tools used to generate ‘omic’ data and computational frameworks to interpret this data. Through illustrative examples, systems biology approaches to understand gene expression and gene expression regulation are discussed. Some of the challenges facing this field and the future opportunities in the systems biology era are highlighted.     

Paper alert: Plant biology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in plant biology.     

系统生物学

分析了生命复杂性问题的产生及其由来,从复杂性问题研究的角度对系统科学与系统生物学的含义及其相互关系进行了深入的讨论。     

Cell biology

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Plant Biology.     

Reproductive biology of Lactoris fernandeziana (Lactoridaceae)

Lactoris fernandeziana, monotypic in its family, is endemic to the cloud forests of Robinson Crusoe Island. Although there has been considerable study of the relationships of Lactoris, as a rare species and as a putative primitive paleoherb, little is known of its reproductive biology. Knowledge of the latter is essential for effective conservation programs. The species is gynomonoecious. The overall proportion of flowers is ∼1 female:1 hermaphrodite. The inconspicuous semipendulous green flowers, usually in mixed-gender inflorescences, do not produce rewards. Hermaphrodite flowers are herkogamous and protogynous. Pollen grains are shed from the extrorse anthers in permanent dry tetrads. There is a mean of 12879 tetrads per hermaphrodite flower. Both flower types bear an average of ∼18 ovules. The P/O (pollen/ovule) ratios imply facultative or obligate xenogamy, but hand pollinations show that Lactoris is self-compatible. No floral visitors were ever observed, but stigmata of open-pollinated flowers bore tetrads, and 64% of such styles had pollen tubes. Flowers enclosed in large mesh (1 mm) bags bore similar numbers of tetrads and pollen tubes. Thus, we conclude that Lactoris is anemophilous, a syndrome perhaps reflected by the P/O ratio. Low genetic diversity (isozymes and DNA) supports selfing and implies limited distance wind pollen dispersal. The small size of the island, the ± 1000 extant Lactoris plants, coupled with anemophily, self-compatibility, and pendant flower position, have yielded a geitonogamous system with high seed set and low genetic diversity. If inbreeding depression is expressed, it is in seed germination and seedling vigor, for Lactoris is very difficult to cultivate. For this species, effective conservation practices need to focus on habitat preservation and promotion of outcrossing.     

Network design meets in silico evolutionary biology

Cell fate is programmed through gene regulatory networks that perform several calculations to take the appropriate decision. In silico evolutionary optimization mimics the way Nature has designed such gene regulatory networks. In this review we discuss the basic principles of these evolutionary approaches and how they can be applied to engineer synthetic networks. We summarize the basic guidelines to implement an in silico evolutionary design method, the operators for mutation and selection that iteratively drive the network architecture towards a specified dynamical behavior. Interestingly, as it happens in natural evolution, we show the existence of patterns of punctuated evolution. In addition, we highlight several examples of models that have been designed using automated procedures, together with different objective functions to select for the proper behavior. Finally, we briefly discuss the modular designability of gene regulatory networks and its potential application in biotechnology.     

Reproductive biology of Trichocentrum pumilum: an orchid pollinated by oil-collecting bees

The reproductive biology, reward production and pollination mechanism of Trichocentrum pumilum were studied in a gallery forest in the interior of the State of São Paulo, southeast Brazil. The floral visitors and pollination mechanism were recorded, and experimental pollinations were carried out in order to determine the breeding system of this species. Trichocentrum pumilum blooms in spring. Each paniculate inflorescence bears an average of 85 flowers that present a central yellow callus and finger‐like trichomes on the lateral lobes of the lip. A lipoidal substance is produced and stored among these trichomes. In the studied population, T. pumilum is exclusively visited and pollinated by two bee species (Tetrapedia diversipes and Lophopedia nigrispinis). Pollinaria are deposited on mouthparts of bees during collection of the lipoidal substance from the lateral lobes of the labellum. Trichocentrum pumilum is self‐incompatible and pollinator‐limited. Natural fruit set was low (9%, compared to 45% in experimentally cross‐pollinated flowers). Potentially viable seed exceed 97% in fruits obtained through cross‐pollination and in natural conditions (open pollination).