RESEARCH
Glyco-Molecular Science Division
Purpose / Contents
Understanding the behaviors of each glycan molecule
In the Glyco-Molecular Science Division in the integrated Glyco-Molecular Science Research Center (iGMOL), our goal is to elucidate the principles of the behavior of individual glycans in cells. To achieve this, we aim to synthesize individual glycans, elucidate their biosynthetic mechanisms, and determine their structures. Additionally, we analyze the dynamics of individual glycans by utilizing single molecule imaging with synthesized glycan probes and NMR. Glycan-related metabolites are also analyzed for their structure and quantity.
Through these approaches, we will clarify the dynamic behavior and biosynthetic mechanisms of each glycan molecule in living cells. Integrating the knowledge about individual glycans will lead to a better understanding and regulation of their behaviors, biosynthesis, and overall functions.
Examples
Innovation of glycan synthesis
For example, we have recently developed a new innovative method for chemical synthesis of sialylated glycans (Komura et al., Science, 2019, 364, 677-680). Developing such techniques, we try to construct glycan libraries.
The fastest single glycan imaging
We also develop novel glycan probes by labeling glycans with fluorescence or search for new glycan binding molecules. Using these probes, we visualize the dynamics of a single glycan in cell membrane (Komura et al., Nat. Chem. Biol., 2016, 12, 402-410).
Understanding, prediction and remodeling of glycan biosynthesis
We focus on glycan-biosynthetic enzymes (glycosyltransferases) and aim to elucidate the mechanisms of their reactions and regulation using biochemical and genetic approaches. We also integrate glycosyltranasferase data to predict and remodel cellular glycan structures (Nagae et. al., Nat. Commun., 2018, 9, 3380, Huang et. al., Dev. Cell, 2021, 56, 1195-1209).
Members List
Hiromune Ando
Vice-DirectorDivision of Glyco-Molecular Science
- Research interests
- Carbohydrate chemistry, chemical biology, sialic acid, molecular probe, virus infection
- Research subject
- We particularly focus on the chemical synthesis of glycans containing sialic acid, which is a sugar present on the cell surface. Sialic acid-containing glycans are closely related to diseases, such as viral invasion and malignant transformation of cancer. We have developed a powerful method for chemical synthesis and succeeded in synthesizing more than 300 kinds of sialic acid-containing glycans. Recently, we have succeeded for the first time in the world in visualizing dynamically moving glycans in the plasma membrane of living cells through interdisciplinary research with biophysics. By further advancing such research, we aim to unveil the real picture of glycans, which has not been possible to observe, and to understand the functions of glycans in biological processes.
Yasuhiko Kizuka
ChairDivision of Glyco-Molecular Science
- Research interests
- Glycosyltransferase, N-glycan
- Research subject
- We focus on glycosyltransferases which form branching structures of N-glycans and try to reveal the regulation mechanisms of their activity and disease relevance. We take a biochemical approach in combination with structural biology, chemistry, and glycomics. We have revealed that deficient mice for a specific glycosyltransferase show the improved Alzheimer’s disease pathology, and tertiary structures and acceptor protein selectivity of cancer-related glycosyltransferase GnT-V and diabetes-related GnT-IV. Moreover, we develop glycan probes and glycosyltransferase inhibitors.
Kenichi G. N. Suzuki
Division headDivision of Glyco-Molecular Science
- Research interests
- Single molecule imaging, super resolution imaging, glycolipid, GPI-anchored protein, signal transduction
- Research subject
- Using single molecule and super-resolution imaging techniques, we aim to elucidate the organization and functions of cell membranes. In particular, we aim to elucidate the roles of glycans in dynamic microdomain formation on living cell membranes and in the promotion and regulation of signal transduction.
Hideharu Ishida
Division of Glyco-Molecular Science
- Research interests
- Bioactive compound, enzyme inhibitor, ligand of lectin, immune regulation
- Research subject
- We focus on proteins that recognize glycans (glycosidases and lectins) and design and synthesize their inhibitors or antagonists to develop biologically active compounds. We have succeeded in developing an inhibitor of influenza virus sialidase, a selective inhibitor that acts only on NEU1 among the four types of human sialidases, and an antagonist of the inhibitory B cell receptor siglec-2. These compounds have been applied to elucidate the pathogenesis of related diseases and to control biological reactions.
Tomio Yabe
Division of Glyco-Molecular Science
- Research interests
- Proteoglycan, heparan sulfate, sulfation pattern, dietary fiber, intestinal epithelial cell
- Research subject
- We aim to elucidate the regulatory mechanism of physiological actions of heparan sulfate by controlling sulfation patterns in heparan sulfate. In particular, we focus on the mechanism of action of intestinal epithelial cells that respond specifically to the polysaccharide structure of dietary fiber. We analyze the mechanism by which heparan sulfate structures at the basement membrane are regulated by interaction between cell surface proteins and dietary fiber.
Masato Ikeda
Division of Glyco-Molecular Science
- Research interests
- Supramolecular chemistry, nanobiomaterial, chemical biology
- Research subject
- We design and synthesize new hybrid molecules that have multiple molecules as modules, including glycans. We study their biological functions, construction of nanostructures by molecular assembly, and generation of biofunctional materials.
Morihisa Fujita
Division of Glyco-Molecular Science
- Research interests
- Endoplasmic reticulum, intracellular trafficking, GPI-anchored protein, glycan remodeling
- Research subject
- We focus on the "life cycle of glycoproteins (biosynthesis, intracellular transport, and degradation)" and aim to elucidate the regulatory mechanisms of the life cycle of glycoproteins. In particular, we analyze the biosynthesis and intracellular dynamics of glycosylphosphatidylinositol (GPI)-anchored proteins and paucimannose-containing glycoproteins using genetic, biochemical, and cytological methods. Furthermore, we aim to develop tools to visualize glycan metabolic pathways and to construct glycan-modified host cells, for producing biopharmaceutical glycoproteins.
Natsuhisa Oka
Division of Glyco-Molecular Science
- Research interests
- Franoside, stereoselective synthesis, domino reaction, inositol, carbasugar
- Research subject
- We develop efficient methods for the synthesis of various chiral cyclopentenes and cyclohexenes by domino reaction using heteroarylsulfones derived from sugars. We will explore efficient routes to convert the resulting cyclopentenes and cyclohexenes into useful compounds such as bioactive natural products, inositol derivatives, and carbasugars.
We also develop a highly stereoselective furanosylation reaction using iodinated sugars as glycosyl donors. This reaction proceeds with complete 1,2-cis selectivity and efficiently yields stereochemically pure furanosides. We aim to use this reaction for efficient synthesis of cell surface glycans.
Hide-Nori Tanaka
Division of Glyco-Molecular Science
- Research interests
- Glycan, ADP ribose chain, selective synthesis, protection-free synthesis, chemoenzymatic synthesis
- Research subject
- Based on synthetic chemistry, we aim to unveil and manipulate the biological functions of glycans and ADP-ribose chains, which are post-translational modifications of proteins.
Synthetic chemistry is extremely important in life science research because it can provide molecules that are structurally homogeneous and pure, but the synthesis of these molecules requires a great deal of effort and time. This has been the bottleneck in research on both molecules. Therefore, I work on the rapid and efficient synthesis of glycans and ADP-ribose chains by using selective synthesis, protection-free synthesis, and chemoenzymatic synthesis. Our unique synthetic chemistry will break through the bottleneck and dramatically advance life science focusing on both molecules.
Naoko Komura
Division of Glyco-Molecular Science
- Research interests
- Sialic acid, ganglioside, lipid rat
- Research subject
- We are engaged in chemistry study on sialic acid-containing glycans and chemical biology study using the synthesized glycans. In particular, we focuse on the functions of sialic acid-containing glycolipids (gangliosides) in lipid rafts, which are responsible for signal transduction on the cell membrane.
Akihiro Imamura
Division of Glyco-Molecular Science
- Research interests
- 有機合成、反応開発、糖脂質
- Research subject
- 有機化学的手法による糖鎖合成および糖の誘導化に必要な反応開発。単糖の誘導化からオリゴ糖、多糖まで幅広くターゲットにし、糖鎖科学の発展に寄与する糖誘導体を創出している。
Rinshi S. Kasai
Division of Glyco-Molecular Science
- Research interests
- G-protein coupled receptor, dimer/oligomer formation, secreted glycoprotein, in-plane cell polarity, single molecule imaging techniques
- Research subject
- Focusing on signal transduction pathways involved in cell polarity, we aim to elucidate the mechanisms of novel intercellular communication mediated by extracellular vesicles including secretory glycoprotein Wnt. In order to observe the molecules exchanged between cells and to quantify the intracellular signals generated by them, we develop and use several fluorescence microscope-based methods to study molecular behavior, such as single molecule tracking, dimer/oligomer quantification, and super-resolution observation.
Yoshinori Muto
Division of Glyco-Molecular Science
- Research interests
- Bioinformatics, anaerobic bacteria, genome, sphingolipid, molecular evolution
- Research subject
- Using bioinformatics methods, we conduct comparative genomic and molecular evolutionary analyses of anaerobic bacteria to elucidate drug resistance and host symbiosis mechanisms. We also focus on the biological functions of sphingolipids in gut-commensal anaerobic bacteria, and study the molecular evolution of metabolic enzymes and their relationship to the host (human).
Research Division
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