Image source: Dynamics and Interactions of OmpF and LPS / Biophysical Journal Volume 110

Glyco-lipidologue Initiative

Our body is consisted of four major macromolecules – glycans, lipids, nucleic acids, and proteins. The “Central Dogma” of biology has explained how proteins are unequivocally defined by the genome (DNA), and for this reason, genome has been considered the blueprint of life. Glycans and lipids, on the other hand, remain as enigmatic bodies not directly controlled by genome; for instance, their structures are often altered in a flexible fashion by various environmental factors.

The uniqueness of glycans and lipids is their unusual complexity: on top of their structural diversity, their composition is drastically different among organelles, cells, tissues and organisms. They can also exhibit multifaceted functionality, for instance, by forming homo- or heteropolymers or complexes. To gain deeper insight into the secret of structural diversity, spatial heterogeneity, and functional polymorphism of glycans/lipids, interdisciplinary approach is essential. In addition to the state-of-the-art RIKEN-original methods for imaging, synthesis, and detection, we integrate the comprehensive, panoramic protocols called “-omics” to clarify the complexity of glycans and lipids.

In this pioneering project, we seek to clarify the “Glyco-lipidologue” i.e. language (=logos) of glycans and lipids toward the full understanding of their diversity, heterogeneity, and polymorphism. Through this research, we also contribute to elucidate complex biological phenomena, such as lifestyle-oriented disease, molecular evolution or gastrointestinal environment from the perspective of glycans and lipids (Figure 1).

Figure 1. Outline of Glyco-Lipidologue Initiative Figure 1. Outline of Glyco-Lipidologue Initiative: Through the power of interdisciplinary collaboration, we aim to clarify the biological meaning of structural diversity, spatial heterogeneity and functional polymorphism of glycans/lipids. 学際的なコラボレーションの力を通じて、糖鎖/脂質の構造的多様性、空間的不均一性、機能的多型の生物学的意味を明らかにすることを目指しています。


我々の体は、DNA, RNA等の核酸に加え、タンパク質、脂質、糖質で構成されています。いわゆるセントラルドグマの考え方では、タンパク質の構造がDNAによって一義的に決定され、DNAこそが生命の設計図となることは周知の事実です。しかし、脂質や糖質などのDNA非コード分子の構造は外的環境に依存して柔軟に組成や構造を変え、その構成要素も、自身による合成に加え、食物などの外的因子に大きく左右され得ることが知られています。


近年、生命の分子進化や生活習慣病をはじめとした疾患、腸内を含む生物共生環境がゲノムのみからは解き明かせず、脂質、糖質の理解が不可欠であることが明らかになりつつあります。我々は独自の技術で脂質、糖質機能を俯瞰的、系統的に理解し、体系化することを目指します。そして脂質、糖質の分析技術を理研内外に幅広く提供するための研究“ハブ”を形成します。多くの研究者が脂質、糖質研究に参入できる道を拓くことで、4つの生体高分子(タンパク質、核酸、脂質、糖質)を統合した生命の理解を目指し、最終的には“glyco-lipidologue” - 生物界で多様な糖質、脂質が、階層性、多相性を生み出すことの本質的な意義 - を理解することを目標とします。

Sub-Project 1: In silico Platform

The “Glyco-lipidologue Initiative” aims to understand the meaning of incredibly varied glyco- and lipid molecules in biological systems. This sub-project, “In silico Platform” functions as a glue to integrate research outcomes from the other two sub-projects using bioinformatics. Through computation, we aim to theorize biological data into reproducible, reusable knowledge. This knowledge is then used for hypothesis generation for the other two sub-projects to create an iterative cycle to improve research. Such knowledge is also essential for connecting researchers in and outside of RIKEN.


Sub-Project 1: In silico Platform image

Sub-project Leader:
Masanori Arita (Metabolome Informatics Team, CSRS)

Yuji Sugita (Theoretical Molecular Science Laboratory, CPR)

Sub-Project 2: Innovative tool development

“Glyco-lipidlogue Initiative” aims to understand the meanings of super-diversity of glycans and lipids found in the biological systems. This sub-project will provide a set of basic tools for the analysis of glycan/lipid (G/L) variations in structural diversity, spatial heterogeneity, and functional polymorphism in the biological systems, which we call “glycan/lipid (G/L) landscape” over the scales of tissues, cells, and organellae.

本サブプロジェクトは、glyco-lipidologue研究の基盤として、糖質・脂質の多様性・階層性・多相性の実体 ”glycan/lipid (G/L) landscape (糖質・脂質の分子地形)” を詳細に解析する画期的な技術を、統合したパッケージとして開発します。

Sub-Project 2: Innovative tool development image

Sub-project Leader:
Yasushi Sako (Cellular Informatics Laboratory, CPR)

Makoto Arita (Laboratory for Metabolomics, IMS)
Tadashi Suzuki (Glycometabolic Biochemistry Laboratory, CPR)
Katsunori Tanaka (Biofunctional Synthetic Chemistry Laboratory, CPR)

Sub-Project 3: Advanced Biology

This sub-project will study various functional roles of glycans/lipids and their protein complexes in specific biological contexts by taking a full advantage of research tools and/or bioinformatics provided by other sub-projects. We realize that distributions of various biomolecules can be a consequence of metabolism/homeostasis in cells/organisms, therefore we aim for the understanding of the whole pictures of their biosynthesis/catabolisms and their defects under pathophysiological conditions. We also aim at clarifying the dynamics of molecular complexes involving glycans/lipids.


Sub-Project 3: Advanced Biology image

Sub-project Leader:
Tadashi Suzuki (Glycometabolic Biochemistry Laboratory, CPR)

Hiroyuki Kamiguchi (Laboratory for Neural Cell Dynamics, CBS)
Yasushi Sako (Cellular Informatics Laboratory, CPR)