Biotechnology Research Institute for Drug Discovery
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Glycoscience and Glycotechnology Research Group

Proteins which are secreted into body fluids, such as blood, and those integrated into the membrane, e.g., cell surface, are mostly glycosylated. The attached glycans are considered to play an important role to express and regulate the glycoprotein functions. However, the analysis of glycan functions is technically difficult due to the diverse and heterogeneous structure of glycans. Thus far, a series of technologies to analyze protein glycosylation has been developed at AIST. We applied them to develop disease glycobiomarkers and succeeded in commercialization of a marker M2BPGi to assess the degree of liver fibrosis. Currently, we are consulting on further development of the technologies for structural analysis, production, modification, detection, and information analysis of glycoproteins aiming at development of other biomarkers and seeds for therapeutic agents and at translation of them to the society.

Group's Research Theme

Glycomics & glycoproteomics technologies

Development and application of the technologies for glycomics and glycoproteomics

It is essential to reveal the status and alteration of glycome and glycoproteome in tissues and body fluids for development of disease glycobiomarkers and glyco-targeting drugs. To achieve this, we establish a series of glycomic and glycoproteomic technologies based on the lectin array and mass spectrometry (MS), and apply them to contribute to development of diagnostic and therapeutic agents.

Glycoprotein production by yeast cells and enzymatic reactions and its application
 





Glycoprotein production by yeast cells and enzymatic reactions and its application

We develop the technologies to produce glycoproteins with desired glycan structures for development of novel biomarkers and innovative drugs related to glycans.
Since the yeast is eukaryote and can secrete glycoproteins, it is expected to be one of good organism as a production host of glycoproteins. We therefore proceed with analyses of the enzymes related to yeast glycans, GPI-anchor biosynthesis, and glycan hydrolases. We also develop yeast cells that can produce human-compatible glycans and glycoproteins by molecular breeding of biosynthetic pathways in the yeast cells. Production of glycoproteins with homogeneous glycans by the activity of several glycosyltransferases and glycosidases is also one of our objectives and goals. The produced glycoproteins could be used for innovative drug development and as a tool for biomarker detection.

Disease-related phenotypes of glycogene-modified mice
Disease-related phenotypes of
glycogene-modified mice







Functional analysis using glycan modification technology

Protein glycosylation is controlled by the products of glycogenes, such as glycosyltransferases and sulfotransferases localized in the endoplasmic reticulum and Golgi apparatus. To clarify the functions of glycans, the most direct method is alteration of glycogene expressions. However, glycan synthesis is a consequence of coordinated and competitive enzyme reactions of about 200 kinds of glycogenes. Therefore even a change of single gene expression may cause various structural changes of glycans resulting in several functional changes. In our group, glycogene-modified cell lines and mice are generated and analyzed by glycoproteomics technologies to identify in detail that “which glycans, at which sites, and on which proteins” are affected by modification of one specific gene. We also analyze the changes in cellular functions including proliferation, metastatic potential, and viability and the disease-related phenotypes such as cancer, immunity, and infection aiming comprehensive understanding of structures and functions of glycans.

Enhancement of the integrated glycoscience database and international collaboration
 









Enhancement of the integrated glycoscience database and international collaboration

Our group has been participating in the integrated database project of the National Bioscience Database Center (NBDC), Japan Science and Technology Agency (JST), to convert the various databases of glycoscience in Japan into semantic web so that a broad field of scientists can efficiently use the accumulated data. Moreover, we collaborate with the researchers in other Asian countries and serve as the management and secretariat of the information infrastructure as resources of the Asian Community of Glycoscience and Glycotechnology (ACGG) to support establishment of the cooperative framework. We also contribute to the establishment and maintenance of the international glycan structure repository system (GlyTouCan) in cooperation with other research institutes aiming not only advancement of the glycan-related database but also enhancement of the international collaboration systems.

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Research Achievements

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Staff Members

Position & Name Email Address & Web SiteWeb Site
Group Leader
Hiroyuki KAJI
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Principal Research Manager
Hisashi NARIMATSU
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Chief Senior Researcher
Yasunori CHIBA
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Chief Senior Researcher
Atsushi KUNO
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Senior Researcher
Takehiko YOKO-O
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Senior Researcher
Akira TOGAYACHI
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Senior Researcher
Takashi SATO
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Researcher
Chiaki NAGAI-OKATANI
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Web Sitehttp://researchmap.jp/nagaic/
Invited Senior Researcher
Kiyohiko ANGATA
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Invited Senior Researcher
Nobuyoshi TAKASAKI
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Invited Senior Researcher
Toshihide SHIKANAI
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AIST Postdoctoral Researcher
Elena SOLOVIEVA
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AIST Postdoctoral Researcher
Erika NORO
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