UniCarbKB: putting the pieces together for glycomics research

Despite the success of several international initiatives the glycosciences still lack a managed infrastructure that contributes to the advancement of research through the provision of comprehensive structural and experimental glycan data collections. UniCarbKB is an initiative that aims to promote the creation of an online information storage and search platform for glycomics and glycobiology research. The knowledgebase will offer a freely accessible and information-rich resource supported by querying interfaces, annotation technologies and the adoption of common standards to integrate structural, experimental and functional data. The UniCarbKB framework endeavors to support the growth of glycobioinformatics and the dissemination of knowledge through the provision of an open and unified portal to encourage the sharing of data. In order to achieve this, the framework is committed to the development of tools and procedures that support data annotation, and expanding interoperability through cross-referencing of existing databases. Database URL: http://www.unicarbkb.org.     

国际糖生物学战略布局与研究前沿分析

糖生物学与细胞信号转导、发育、免疫等许多领域相关联,是全面、深入理解生命活动所必需的。本文通过分析各国在糖生物学领域的战略布局,并使用ISI Essential Science Indicators数据库和VOS Viewer软件从定量角度分析国际糖生物学领域的研究前沿,为我国制定糖生物学研究相关战略提供借鉴。     

Quantitation by isobaric labeling: applications to glycomics

The study of glycosylation patterns (glycomics) in biological samples is an emerging field that can provide key insights into cell development and pathology. A current challenge in the field of glycomics is to determine how to quantify changes in glycan expression between different cells, tissues, or biological fluids. Here we describe a novel strategy, quantitation by isobaric labeling (QUIBL), to facilitate comparative glycomics. Permethylation of a glycan with (13)CH 3I or (12)CH 2DI generates a pair of isobaric derivatives, which have the same nominal mass. However, each methylation site introduces a mass difference of 0.002922 Da. As glycans have multiple methylation sites, the total mass difference for the isobaric pair allows separation and quantitation at a resolution of approximately 30000 m/Delta m. N-Linked oligosaccharides from a standard glycoprotein and human serum were used to demonstrate that QUIBL facilitates relative quantitation over a linear dynamic range of 2 orders of magnitude and permits the relative quantitation of isomeric glycans. We applied QUIBL to quantitate glycomic changes associated with the differentiation of murine embryonic stem cells to embryoid bodies.     

Establishment of an efficient germ-free animal system to support functional microbiome research

正Germ-free animals are indispensable models for human and animal functional microbiome research Germ-free animals are animals that typically have no microorganisms living in or on them. These animals have become irreplaceable research tools for studying the relationships among single bacteria strains, multiple bacteria strains and hosts.     

Lectin-based structural glycomics: Glycoproteomics and glycan profiling

Structural glycomics (SG) plays a fundamental part of concurrent glycobiology aiming at comprehensive elucidation of glycan functions ( i.e. , functional glycomics) in the context of post-genome sciences. The SG project started in April 2003 and will continue for 3 years in the framework of NEDO (New Energy and Industrial Technology Organization) under the METI (the Ministry of Economy, Trade, and Industry), Japan. The main purpose of the project is the development of high-throughput and robust machines, which should greatly contribute to the structural analysis of complex glycans. In this chapter, 2 major research items, i.e. , (1) glycoproteomics, which enables comprehensive analysis of glycoproteins, and (2) "glycan profiling" by means of lectins, are described. For the latter, frontal affinity chromatography has been adopted as a starting tool for comprehensive analysis of the interaction of 100 lectins and 100 oligosaccharides under the concept of "hect-by-hect," which refers to 100 x 100.     

Insect glycobiology: a lectin multigene family in Drosophila melanogaster.

Glycodeterminants play an important role in mediating cellular and cell-substrate interactions during development and immune-related reactions enabling an organism to distinguish self determinants from non-self or modified-self determinants. One of the hallmarks of sugar recognition molecules (lectins) is their wide range of binding activities and their organisation in multigene families. Here we describe a group of Drosophila genes that are possible members of the C-type lectin family.     

On an infrastructure to support sharing and aggregating pre- and post-publication systems biology research data

The move towards in silico experimentation has resulted in the use of computational models, in addition to traditional experimental models, to generate the raw data that is analysed and published as research findings. This change requires new methods to be introduced to facilitate independent validation of the underlying models and the reported results. The promotion of co-operative research has the potential to help to both validate results and explore wider problem areas. In this paper we leverage and extend two existing software frameworks to develop an infrastructure that has the potential to both promote the sharing of data between researchers pre-publication and enable access to the data for interested parties post-publication. The pre-publication sharing of data would enable larger problem spaces to be explored by distributed research groups; enabling access to the data post-publication would allow reviewers and the wider community to independently verify the published results which would, in the longer term, help to increase confidence in published results. The framework is used to perform reproducible and numerically validated individual-based computational experiments into the onset of colorectal cancer. Existing results are verified and new insights into the top-down versus bottom-up hypothesis of colorectal crypt invasion are given.     

European policy review: Biodiversity research to support European policy

Biodiversity research is essential to underpin the development, implementation and evaluation of policy that impacts on or protects biodiversity. An example is presented on how European terrestrial biodiversity research is being integrated to strengthen policy input. ALTER-Net is a Long-Term Biodiversity, Ecosystem and Awareness Research Network funded by the 6th European Union Framework Programme for Research and Development.     

Structural glycobiology: a game of snakes and ladders

Oligo- and polysaccharides are infamous for being extremely flexible molecules, populating a series of well-defined rotational isomeric states under physiological conditions. Characterization of this heterogeneous conformational ensemble has been a major obstacle impeding high-resolution structure determination of carbohydrates and acting as a bottleneck in the effort to understand the relationship between the carbohydrate structure and function. This challenge has compelled the field to develop and apply theoretical and experimental methods that can explore conformational ensembles by both capturing and deconvoluting the structural and dynamic properties of carbohydrates. This review focuses on computational approaches that have been successfully used in combination with experiment to detail the three-dimensional structure of carbohydrates in a solution and in a complex with proteins. In addition, emerging experimental techniques for three-dimensional structural characterization of carbohydrate-protein complexes and future challenges in the field of structural glycobiology are discussed. The review is divided into five sections: (1) The complexity and plasticity of carbohydrates, (2) Predicting carbohydrate-protein interactions, (3) Calculating relative and absolute binding free energies for carbohydrate-protein complexes, (4) Emerging and evolving techniques for experimental characterization of carbohydrate-protein structures, and (5) Current challenges in structural glycoscience.     

From lectin structure to functional glycomics: principles of the sugar code

Lectins are carbohydrate-binding proteins which lack enzymatic activity on their ligand and are distinct from antibodies and free mono- and oligosaccharide sensor/transport proteins. Emerging insights into the functional dimension of lectin binding to cellular glycans have strongly contributed to the shaping of the 'sugar code'. Fittingly, over a dozen folds and a broad spectrum of binding site architecture, ranging from shallow grooves to deep pockets, have developed sugar-binding capacity. A central question is how the exquisite target specificity of endogenous lectins for certain cellular glycans can be explained. In this regard, affinity regulation is first systematically dissected into six levels. Experimentally, the strategic combination of methods to monitor distinct aspects of the lectin-glycan interplay offers a promising perspective to answer this question.