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The fundamental structure of biomembranes is a lipid bilayer which can be reconstituted using a single species of lipids. However, there are thousands of lipid molecular species in our body. Although the reason for this diversity of lipids is not elucidated, recent advance in the field uncovered the role of minor lipid components as lipid messengers and the importance of the assembly of lipid molecules as platforms of signal transduction as well as membrane traffic. Many diseases such as atherosclerosis, heart disease and metabolic syndrome are known as lipid disorders. However, unlike proteins, lipids are not the primary product of nucleic acids. In addition, the water-insoluble, yet amphiphilic nature of lipids adds an additional layer of complexicity to these experiments. Because of these specific properties and the sheer number of lipid species, lipid research is lagging behind the research of proteins and nucleic acids. However, recent advances of mass spectrometry and microscope techniques enabled the study of metabolism, distribution and dynamics of individual lipid.

In this project, we will employ highly original techniques of advanced lipid research, such as lipid imaging, single cell mass spectrometry and single molecular dynamics of lipids and proteins, to elucidate the fundamental functions of lipids. We will also try to develop novel diagnostic, curative and preventing methods for the treatment and prevention from lipid disorders.

We will perform the project as a collaboration of 3 sub-projects. The Advanced Lipidomics sub-project is focusing the development of lipid-specific probes to visualize lipids which will be used in the whole project. This group also screens inhibitors/regulators of lipid metabolism/distribution /dynamics which will be used in other sub-groups. In addition, this group will analyze lipid samples from the whole group using comprehensive and one-cell mass spectrometry. The Molecular Protein Lipidology sub-group will study molecular interaction of lipids and proteins. The Dynamic Lipid Physiology sub-group will study the function of lipids in neurons, immune cells and adipocytes as collaboration with other sub-groups. We believe that the successful collaboration will provide the new concept in lipid biology.

Lead researcher 2014-2015: Toshihide Kobayashi (Lipid Biology Laboratory)

In the fiscal year of 2016, “Integrated Lipidology” has embarked on its third year as part of RIKEN’s pioneering projects. Along with the transfer of the Integrated Lipidology project founder Toshihide Kobayashi to the French National Center for Scientific Research (CNRS), the project was restructured at the end of the year 2015. We welcomed Masanori Arita, team leader at RIKEN Center for Sustainable Resource Science (CSRS), as the leader of our sub-project: Advanced Lipidomics. At the same time, I have assumed the role of the overall representative of the project, while Research Director Kobayashi will be joining the research from abroad as a major member of the project.

Even when simply referring to the topic of lipids, the width of their range of roles cannot be underrated. To maintain its integrity as a functional unit of life, it is indispensable for cells that lipids form a bilayer to separate the organelles from the outer-cell environment. Lipids that possess diverse molecular characteristics are unevenly distributed on the bilayer and they form domains that integrate specific membrane proteins in order to carry out a highly efficient intracellular signaling. In addition, free fatty acids act as mediators in the intestine, pancreas, adipose tissue, immune cells, nervous system, etc., thereby involving in activities such as maintenance of homeostasis and formation of neural circuitry. Furthermore, various lipid metabolites by gut microbiota affect human health in conditions such as lifestyle diseases.

Up to this point, our project has been able to clarify a part of the roles of the abovementioned lipids. From 2016 onwards, we will continue to promote the search for novel functions of lipids and the elucidation of its principles through a combination of further strengthening the joint research efforts and use of lipid analysis techniques accomplished in each of our sub-projects up until last year. Hereby, I would like to strive for an understanding of lipid bioregulatory systems across the hierarchical organization of life from the molecular level to the organism.

Lead researcher since 2016: Yasushi Sako (Cellular Informatics Laboratory)

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