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Group Introduction

Structure Physiology Research Group

Introduction to research

We investigate the structure of protein complexes, cells and tissues using a combination of Transmission Electron Microscopy (TEM), our original Atmospheric Scanning Electron Microscopy (ASEM) and molecular dynamics (MD). By combining large numbers of TEM images using single particle analysis (SPA), we determine a high-resolution 3D structure of various membrane proteins complexes using our newly-developed image analysis algorithms. We have developed an in-solution observation microscope ASEM and other environmental microscopy techniques. We develop new MD methodologies. These are applied to study the molecular mechanisms of signaling complexes, including ion channels, receptors, and antibodies. Cell level techniques are also developed to study carcinogenesis and metastasis.

  • Development of cryo-TEM single particle reconstruction and environmental microscopies
  • Development of new molecular dynamics method
  • Study of Carcinogenesis and cancer metastasis
  • Development of immune technologies and antibody productions

  • For example, structure determination of membrane proteins is important to understand the signaling systems in our cells and also for drug design. However, their crystallization is generally hard. We have been developing structure determination methods using cryo-TEM without protein crystals (SPA) for more than ten years. This methodology recently reached atomic resolution and is expected to be widely applied to determine the structure of membrane proteins and molecular complexes. We focus on solving the mechanisms of the signaling proteins and their complexes, including channels, receptors and sensors, to understand the molecular machinery realizing our physiological functions.

    Structure of IP3 receptor revealed by TEM reconstruction

    ASEM has been developed to realize high resolution observation of a sample immersed in aqueous liquid in a readily accessible, open ASEM dish. Fixed cells or tissues in radical scavenger solution (10 mg/ml glucose) can be directly observed by SEM through a thin silicon nitride (SiN) film in the base of the ASEM dish. The observable depth of ASEM is 2-3 mm and the resolution is 8 nm. Using ASEM, we have successfully observed protein complex formations in cells or in small synaptic connections. It could be applied for quicker intra-operative diagnosis of cancer or infectious diseases.

    ASEM image of fine synapses between neurons

    We combine microscopy techniques and MD method to comprehensively understand the signaling complex formations including channels, immune responses for antibody production, carcinogenesis and metastasis.

    List of Publications

    20172016201520142013201220112010

    Staff:

    • Chikara Sato (Research Group Leader)

    • Toshihiko Ogura

    • Yuto Komeiji

    • Yoshiro Hanyu

    • Joutarou Yamamoto