生物工程与生物物理

生物工程包含众多的领域如细胞工程、酶工程、膜工程、医学生物工程、基因工程、蛋白质工程等.在有限的篇幅内不可能涉及所有方面,本文仅选择遗传工程、蛋白质工程以及膜通道最新的一些进展谈一些粗浅看法,以期引起生物物理学工作者的兴趣来共同关心和促进生物工程有关领域的发展.     

Knowledge sharing and collaboration in translational research, and the DC-THERA Directory

Biomedical research relies increasingly on large collections of data sets and knowledge whose generation, representation and analysis often require large collaborative and interdisciplinary efforts. This dimension of 'big data' research calls for the development of computational tools to manage such a vast amount of data, as well as tools that can improve communication and access to information from collaborating researchers and from the wider community. Whenever research projects have a defined temporal scope, an additional issue of data management arises, namely how the knowledge generated within the project can be made available beyond its boundaries and life-time. DC-THERA is a European 'Network of Excellence' (NoE) that spawned a very large collaborative and interdisciplinary research community, focusing on the development of novel immunotherapies derived from fundamental research in dendritic cell immunobiology. In this article we introduce the DC-THERA Directory, which is an information system designed to support knowledge management for this research community and beyond. We present how the use of metadata and Semantic Web technologies can effectively help to organize the knowledge generated by modern collaborative research, how these technologies can enable effective data management solutions during and beyond the project lifecycle, and how resources such as the DC-THERA Directory fit into the larger context of e-science.     

Lignocellulosic biomass: Biosynthesis,degradation, and industrial utilization

Lignocellulose biomass derived from plant cell walls is a rich source of biopolymers, chemicals, and sugars, besides being a sustainable alternative to petrochemicals. A natural armor protecting living protoplasts, the cell wall is currently the target of intense study because of its crucial importance in plant development, morphogenesis, and resistance to (a)biotic stresses. Beyond the intrinsic relevance related to the overall plant physiology, plant cell walls constitute an exquisite example of a natural composite material that is a constant source of inspiration for biotechnology, biofuel, and biomaterial industries. The aim of the present review is to provide the reader with an overview of the current knowledge concerning lignocellulosic biomass synthesis and degradation, by focusing on its three principal constituents, i.e. cellulose, hemicellulose (in particular xylan), and lignin. Furthermore, the current industrial exploitation of lignocellulose from fast growing fibre crops (such as hemp) is highlighted. We conclude this review by suggesting approaches for further research to fill gaps in our current knowledge and to highlight the potential of biotechnology and bioengineering in improving both biomass biosynthesis and degradation.     

Evolving patterns in a collaboration network of global R&D on monoclonal antibodies

We investigated the evolution process of collaborative inter-organizational network of the research and development (R&D) on monoclonal antibody (mAb) over the past 30 y. The annual detection of the collaboration network provides dynamics on network structures and relationship changes among different organizations. Our research showed continuous growth of the network's scale and complexity due to the constant entry of new organizations and the forging of new partnering relationships. The evolving topological features reveal a core-periphery structure that became clearer over time and an increasing heterogeneity within the collaborative mAb R&D network. As measured by the number of network participants, dedicated biotechnology firms (DBFs) were the dominant organization form in the field of mAb development, but their average centrality was reduced during the period of 2004–2009, when pharmaceutical companies took over the positions of DBFs. Along with the network evolution, 2 waves of substitution on the leading positions were driven by technological innovations and mergers and acquisitions (M&A). In addition, this study analyzed organizational-level behaviors to help understand the evolution of network structures over the field of mAb development across the different technologically innovative or economic contexts.     

Valuable products from biotechnology of microalgae

The biotechnology of microalgae has gained considerable importance in recent decades. Applications range from simple biomass production for food and feed to valuable products for ecological applications. For most of these applications, the market is still developing and the biotechnological use of microalgae will extend into new areas. Considering the enormous biodiversity of microalgae and recent developments in genetic engineering, this group of organisms represents one of the most promising sources for new products and applications. With the development of sophisticated culture and screening techniques, microalgal biotechnology can already meet the high demands of both the food and pharmaceutical industries.By continuing the works and ideas of Dr. Gross, that he could not proceed by himself due a tragic fate in the year 2003, we will keep his place in future not only in the research community but also among all colleagues and other persons who knew him.     

Research Data Management and Libraries: Relationships,Activities, Drivers and Influences

The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a ‘jurisdictional’ driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against the data and model in order to inform ongoing RDM activity.     

Sequence-structure mapping errors in the PDB: OB-fold domains

The Protein Data Bank (PDB) is the single most important repository of structural data for proteins and other biologically relevant molecules. Therefore, it is critically important to keep the PDB data, as much as possible, error-free. In this study, we have analyzed PDB crystal structures possessing oligonucleotide/oligosaccharide binding (OB)-fold, one of the highly populated folds, for the presence of sequence-structure mapping errors. Using energy-based structure quality assessment coupled with sequence analyses, we have found that there are at least five OB-structures in the PDB that have regions where sequences have been incorrectly mapped onto the structure. We have demonstrated that the combination of these computation techniques is effective not only in detecting sequence-structure mapping errors, but also in providing guidance to correct them. Namely, we have used results of computational analysis to direct a revision of X-ray data for one of the PDB entries containing a fairly inconspicuous sequence-structure mapping error. The revised structure has been deposited with the PDB. We suggest use of computational energy assessment and sequence analysis techniques to facilitate structure determination when homologs having known structure are available to use as a reference. Such computational analysis may be useful in either guiding the sequence-structure assignment process or verifying the sequence mapping within poorly defined regions.     

Farm animal genomics and informatics: an update

Farm animal genomics is of interest to a wide audience of researchers because of the utility derived from understanding how genomics and proteomics function in various organisms. Applications such as xenotransplantation, increased livestock productivity, bioengineering new materials, products and even fabrics are several reasons for thriving farm animal genome activity. Currently mined in rapidly growing data warehouses, completed genomes of chicken, fish and cows are available but are largely stored in decentralized data repositories. In this paper, we provide an informatics primer on farm animal bioinformatics and genome project resources which drive attention to the most recent advances in the field. We hope to provide individuals in biotechnology and in the farming industry with information on resources and updates concerning farm animal genome projects.     

传统与未来的碰撞：食品发酵工程技术与应用进展

随着生物技术的飞速发展,作为食品生物工程的主要组成部分,食品发酵工程技术不断升级,在传统发酵食品的菌种、发酵过程、产品品质得到改善的同时,生物制造的功能食品组分、未来食品等新型产品也应运而生。首先概述了由生物技术和信息技术的进步带来的食品发酵研究手段与生产方式的多层面变革,并重点阐释了利用食品合成生物学设计构建细胞工厂的思路和方法,以及食品生物工程在微生物分析、过程工程和分离工程方面的智能化进程。其次,介绍了现代食品生物工程技术在改善传统发酵食品品质及安全性、生产功能食品组分、添加剂和酶制剂、创制未来食品和开发新型益生食品方面的应用进展。最后,对全球和我国食品发酵产业面临的挑战和未来发展趋势进行了总结和展望,以期为食品发酵的技术革新和工业化应用提供参考。     

Environmental Impact of the Production of Mealworms as a Protein Source for Humans – A Life Cycle Assessment

The demand for animal protein is expected to rise by 70–80% between 2012 and 2050, while the current animal production sector already causes major environmental degradation. Edible insects are suggested as a more sustainable source of animal protein. However, few experimental data regarding environmental impact of insect production are available. Therefore, a lifecycle assessment for mealworm production was conducted, in which greenhouse gas production, energy use and land use were quantified and compared to conventional sources of animal protein. Production of one kg of edible protein from milk, chicken, pork or beef result in higher greenhouse gas emissions, require similar amounts of energy and require much more land. This study demonstrates that mealworms should be considered a more sustainable source of edible protein.     

Towards precise reconstruction of gene regulatory networks by data integration

Background: More and more high-throughput datasets are available from multiple levels of measuring gene regulations. The reverse engineering of gene regulatory networks from these data offers a valuable research paradigm to decipher regulatory mechanisms. So far, numerous methods have been developed for reconstructing gene regulatory networks. Results: In this paper, we provide a review of bioinformatics methods for inferring gene regulatory network from omics data. To achieve the precision reconstruction of gene regulatory networks, an intuitive alternative is to integrate these available resources in a rational framework. We also provide computational perspectives in the endeavors of inferring gene regulatory networks from heterogeneous data. We highlight the importance of multi-omics data integration with prior knowledge in gene regulatory network inferences. Conclusions: We provide computational perspectives of inferring gene regulatory networks from multiple omics data and present theoretical analyses of existing challenges and possible solutions. We emphasize on prior knowledge and data integration in network inferences owing to their abilities of identifying regulatory causality.     

Sharing Individual Participant Data from Clinical Trials: An Opinion Survey Regarding the Establishment of a Central Repository

Background

Calls have been made for increased access to individual participant data (IPD) from clinical trials, to ensure that complete evidence is available. However, despite the obvious benefits, progress towards this is frustratingly slow. In the meantime, many systematic reviews have already collected IPD from clinical trials. We propose that a central repository for these IPD should be established to ensure that these datasets are safeguarded and made available for use by others, building on the strengths and advantages of the collaborative groups that have been brought together in developing the datasets.

Objective

Evaluate the level of support, and identify major issues, for establishing a central repository of IPD.

Design

On-line survey with email reminders.

Participants

71 reviewers affiliated with the Cochrane Collaboration''s IPD Meta-analysis Methods Group were invited to participate.

Results

30 (42%) invitees responded: 28 (93%) had been involved in an IPD review and 24 (80%) had been involved in a randomised trial. 25 (83%) agreed that a central repository was a good idea and 25 (83%) agreed that they would provide their IPD for central storage. Several benefits of a central repository were noted: safeguarding and standardisation of data, increased efficiency of IPD meta-analyses, knowledge advancement, and facilitating future clinical, and methodological research. The main concerns were gaining permission from trial data owners, uncertainty about the purpose of the repository, potential resource implications, and increased workload for IPD reviewers. Restricted access requiring approval, data security, anonymisation of data, and oversight committees were highlighted as issues under governance of the repository.

Conclusion

There is support in this community of IPD reviewers, many of whom are also involved in clinical trials, for storing IPD in a central repository. Results from this survey are informing further work on developing a repository of IPD which is currently underway by our group.     

Use of network analysis of metabolic systems in bioengineering

Basic ideas and recent developments in network analysis of metabolic systems and various applications of this analysis in bioengineering are reviewed. Central concepts are the null-space to the stoichiometry matrix and the elementary flux modes. The applicability of elementary-modes analysis in biotechnology is illustrated by the synthesis of the cyclooctadepsipeptides PF1022 in the fungus Mycelia sterilia. Network analysis is also useful in metabolic flux analysis. In particular, a procedure for finding out which reaction rates can be uniquely calculated in underdetermined reaction networks is outlined. The concept of 'enzyme subsets' is explained and its use for analysing genetic regulation is demonstrated. In particular, the correlation between expression data concerning the diauxic shift in yeast and the enzyme subsets in yeast metabolism is discussed.     

Going forward: Increasing the accessibility of imaging mass spectrometry

The driving force behind the high and increasing popularity of imaging mass spectrometry is its demonstrated potential for the determination of new diagnostic/prognostic biomarkers and its ability to simultaneously trace the distributions of pharmaceuticals and their metabolites in tissues without the need to develop expensive radioactively-labeled analogues. Both of these applications would benefit from standardized methods, for the development of novel MS-based molecular histology tests and governmental-approved MS-based assays for pharmaceutical development. In addition, the broader scientific community would benefit from the increased accessibility of the technique. Currently imaging MS studies are individual endeavors, utilizing the individual expertise and infrastructure of a single laboratory and their immediate collaborators. A wide array of tissue preparation, data acquisition and data analysis techniques has been developed but lacks an international collaborative structure and data sharing capabilities. Such a collaborative framework would enable methodological exchange and detailed comparisons of analytical capabilities, to explore synergies between the different methods and result in the development of robust standardized methods. Here we describe the activities of a new European imaging MS network that will explicitly compare and contrast existing methods to provide best practice guidelines for the entire healthcare research community.     

Sustainable mobility indicators for Indian cities: Selection methodology and application

Various indicators of sustainable mobility have been developed. It is difficult to select the most relevant indicators that are useful in a specific context, and that are measurable and achievable at the same time. Indicator selection frameworks – criteria based; causal chains and causal networks have been proposed and used in the past. All three frameworks have certain limitations and strengths.In this study we have proposed a systematic approach of selecting sustainable mobility indicators for Indian cities by combining – criteria based, causal chain and causal network frameworks. The methodology involves both subjective judgments for evaluation of indicators against a set of criteria and objectivity during development and assessment of causal network. The method results in identifying 20 relevant factors for which 32 indicators are shortlisted. Further work is required to develop measurable indicators related to accessibility to the disadvantaged, speed limit restriction and street lighting. These have not been discussed in detail in the existing literature. The 20 factors are classified as root nodes, central and end-of-the-chain nodes that helps in identifying levers of attaining sustainable mobility in Indian cities.The developed causal network is evaluated for its ability to address all sectors associated with sustainable mobility. The causal network has low density and centralization index and therefore accounts for multiple factors. The shortlisted indicators are proposed for preparing low carbon mobility plan (LCMP) for three medium size Indian cities. The indicators are checked for data availability and ease of measurability based on the data collected for preparing the three LCMPs. The analysis shows that the data are available from secondary sources like census to measure root node indicators, whereas central indicators require conducting primary surveys and specific models are required to measure end-of-the-chain indicators.Based on the position of indicators within causal network, it is interpreted that pricing policy, urban form and infrastructure are the levers of sustainable mobility. The indicators of energy consumption, emissions and accessibility are the sustainable mobility targets that we want to achieve.     

Biosecurity in an age of open science

The risk of accidental or deliberate misuse of biological research is increasing as biotechnology advances. As open science becomes widespread, we must consider its impact on those risks and develop solutions that ensure security while facilitating scientific progress. Here, we examine the interaction between open science practices and biosecurity and biosafety to identify risks and opportunities for risk mitigation. Increasing the availability of computational tools, datasets, and protocols could increase risks from research with misuse potential. For instance, in the context of viral engineering, open code, data, and materials may increase the risk of release of enhanced pathogens. For this dangerous subset of research, both open science and biosecurity goals may be achieved by using access-controlled repositories or application programming interfaces. While preprints accelerate dissemination of findings, their increased use could challenge strategies for risk mitigation at the publication stage. This highlights the importance of oversight earlier in the research lifecycle. Preregistration of research, a practice promoted by the open science community, provides an opportunity for achieving biosecurity risk assessment at the conception of research. Open science and biosecurity experts have an important role to play in enabling responsible research with maximal societal benefit.

The risk of biotechnology being misused is growing and may even be increased by moves towards open science. How can we ensure that the goals of both open science and biosecurity are met?     

Engineering biological systems using automated biofoundries

Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges.     

OBPC Symposium: maize 2004 &; beyond—Can agricultural biotechnology contribute to global food security?

Summary Bioengineering approaches provide unprecedented opportunities for reducing poverty, food insecurity, child malnutrition, and natural resource degradation. Genetic engineering offers outstanding potential to increase the efficiency of crop improvement. Thus agricultural biotechnology could enhance global food production and availability in a sustainable way. Small farmers in developing countries are faced with many problems and constraints which biotechnology may assist. Yet, there are varying levels of opposition to the use of this technology in most countries and it is especially intense in Europe. While there is certain public apprehension with the use of bioengineering in food improvement, the primary hurdles facing this technology are the stringent and burdensome regulatory requirements for commercialization, opposition from the special interest groups, apprehension by the food industry especially with the whole foods, and trade barriers including rigid policies on traceability and labeling. Bioengineered crops such as soybean, maize, cotton, and canola with a few traits have already made a remarkable impaet on food production and environmental quality. But, in the developing world, bioengineering of crops such as bananas, cassava, yams, sweet potatoes, sorghum, rice, maize, wheat, millet, and legumes, along with livestock, can elearly contribute to global food security. However, the integration of biotechnology into agricultural research in developing countries faces many challenges which must be addressed: financial, technical, political, environmental, activism, intellectual-property, biosafety, and trade-related issues. To ensure that developing countries can harness the benefit of this technology with minimal problems, concerted efforts must be pursued to create an awareness of its potential benefits and to address the concerns related to its use through dialog among the various stakeholders: policy makers, scientists, trade groups, food industry, consumer organizations, farmer groups, media, and non-governmental organizations. Biotechnology holds great promise as a new tool in the scientific toolkit for generating applied agricultural technologies; however, per se it is not a panacea for the worlds problems of hunger and poverty.     

GEOmetadb: powerful alternative search engine for the Gene Expression Omnibus

The NCBI Gene Expression Omnibus (GEO) represents the largest public repository of microarray data. However, finding data in GEO can be challenging. We have developed GEOmetadb in an attempt to make querying the GEO metadata both easier and more powerful. All GEO metadata records as well as the relationships between them are parsed and stored in a local MySQL database. A powerful, flexible web search interface with several convenient utilities provides query capabilities not available via NCBI tools. In addition, a Bioconductor package, GEOmetadb that utilizes a SQLite export of the entire GEOmetadb database is also available, rendering the entire GEO database accessible with full power of SQL-based queries from within R. AVAILABILITY: The web interface and SQLite databases available at http://gbnci.abcc.ncifcrf.gov/geo/. The Bioconductor package is available via the Bioconductor project. The corresponding MATLAB implementation is also available at the same website.