Members: Core research groups

Four Principal Investigators (PIs) from the Institute for Integrated Cell-Material Sciences (iCeMS), Mineko Kengaku (Director of the CeMI), John Heuser, Aki Kusumi, and Koichiro Tanaka, as well as the Deputy Director of the CeMI, Takahiro Fujiwara (Associate Professor of the iCeMS), form the core group of the CeMI. In addition, iCeMS PI Pete Carlton and the Visiting Professors Fumiyoshi Ishidate, Yoshihiro Oikawa, and Satoshi Ijuin, cooperatively participate in the CeMI.

Mineko Kengaku (Director of the CeMI) / Neuroscience

The brain is an elaborate network of 10 billion neurons that control all our conscious and unconscious behaviors. We seek to understand the mechanism how the brain is constructed by dynamic movement of developing neurons. We also aim to reconstruct cell architectures of the brain in glass dishes for future application to the therapy of damaged brains.

Akihiro Kusumi / Single-Molecule Cell Biophysics

Our laboratory is dedicated to understanding membrane mechanisms and methodology development for single-molecule observation and manipulation at nanometer precisions in living cells. The development is carried out simultaneously with its application to the studies of nano-bioprocesses occurring in living cells, in particular, signal transduction in the cell membrane and the formation and remodeling of the neuronal network. The smooth liaison between physics/engineering and biomedicine is a key for our biomedical research and methodology developments. On the basis of the knowledge of nano-bioprocesses learned in the cells (e.g., partitioning of the plasma membrane into submicron compartments and transient formation of signaling platforms in the cell membrane) and the single-molecule bionanotechnology developed here, we envisage the next-generation nanotechnology, regenerative medicine, and drug discovery protocols.

Koichiro Tanaka / Teraherz Optical Science

This research group investigates terahelz optics and its application to the materials science and biology.

Current main target of the group is high power THz generation, non-liner Thz spectroscopy and near-field imaging of biological systems.

John Heuser / Freeze-Etch Electron Microscopy

Dr. Heuser's laboratory is devoted to visualizing all sorts of biological samples in the electron microscope, everything from whole cells at the 'macro' end of the scale, down to individual macromolecules and macromolecular assemblies or "machines" on the mesoscale. The laboratory is especially involved in developing new procedures of sample preparation for the electron microscope, procedures that can produce a more natural, realistic, and "life-like" appearance of everything in the electron microscope. To accomplish this, the laboratory has pioneered what is called the "quick-freeze/deep-etch" technique of electron microscopy, and has disseminated throughout the world all the equipment and procedures needed to carry out this special procedure. With this technique, Dr. Heuser's laboratory has succeeded in capturing many rapid and fleeting biological events, including the processes of nerve transmission, muscle contraction, viral fusion, and most recently, cell wounding and healing in the process of DNA-transfection.

Peter Carlton / Meiosis, Chromosome Biology, Optical Microscopy

Fluorescence microscopy is incredibly selective, imaging only a few specific kinds of biomolecules among thousands in the cell. However, its resolution has previously been poor, around 250 nanometers at best. Recently, many sub-diffraction microscopy methods have been developed, which provide unprecedented detail of subcellular complexes with light microscopy. Using these imaging methods in combination with genetics and molecular biology we are investigating the structure and dynamic behavior of chromosomes, with the ultimate goal of understanding the activity and transmission of the genome. We are particularly interested in understanding how meiotic chromosomes perform the essential events (pairing, recombination, segregation) of meiosis.

Takahiro Fujiwara (Deputy director of the CeMI)

 Dr. Takahiro Fujiwara has been making pioneering efforts to develop single-molecule imaging techniques in living cells, and to use the methods for understanding the functional mechanisms of the cellular plasma membrane. Recent findings include the following.

(1) The plasma membrane is much more than just a two-dimensional fluid continuum. As a result of its close association with the actin-based membrane skeleton meshwork, the plasma membrane is compartmentalized into “meso-scale” domains with sizes of ~100 nm, giving rise to hop diffusion of membrane molecules among these compartments once every 1-50 ms. Oligomers or clusters of receptor molecules induced by liganding tend to stay much longer than monomers within a compartment, due to decreased intercompartmental hop probability, providing a mechanism for the memory of the location where the external signal was received and for polarized cellular responses.

(2) For a variety of signaling pathways, he has accumulated evidence showing that molecular complexes of three or more molecules transiently (10-300 ms, a time scale much shorter than most cellular signaling time scales) form in and on the plasma membrane, and that these complexes, rather than simple bimolecular collisions, play critical roles in many signaling cascades.

These discoveries were made possible by a method he developed, which allows him to track “single molecules” in “living cells” at “high time resolutions”. Currently, he is developing the research further along this line. In the methodology development front, he is aiming at dual/triple-color simultaneous single fluorescent-molecule observations with a 10-nm (molecular size) spatial precision and the world’s fastest 33-microsecond temporal resolution (the ultimate frame rate for single fluorophores available today). For the research fronts of elucidating the mechanisms for signal transduction and other plasma membrane functions, he will use these technologies to reveal the mechanisms for the formation and function of signaling molecular complexes as well as clathrin-coated pits and caveolae.

Fumiyoshi Ishidate, Visiting Professor

Development and application of microscope imaging technologies, with a special emphasis on confocal laser scanning fluorescence microscopy (single and multi photon.)

Yoshihiro Oikawa, Visiting Professor

Using fluosecent imaging technologies, such as confocal microscopy or  evanescent field microscopy, I am studying the various methods, applications  or optical systems for living cell dynamic imaging.

Satoshi Ijuin, Visiting Professor

Development of application for the biological research of confocal microscope, multi-photon and  super resolution microscope using STED technique.

Koichiro Hirosawa, Research Associate

Single molecule imaging of immuno cell signaling.

Hiroko Hijikata, Research Associate

Preparation of rat primary hippocampal neurons optimized for single fluorescent molecule imaging.

Kazuyoshi Yasugi, Research Support Staff

Yoshiki Sunada, Research Support Staff

Ryota Nakao, Research Support Staff

Satoshi Murata, Research Support Staff

Development of image processing software



World’s Firsts and Bests by the CeMI’s Core PIs

1 Discovered membrane recycling in the cell. 1973, Heuser
2 Invented the "quick-freeze" machine, designed to preserve biological samples for electron microscopic viewing in the most life-like state possible  (named the "slammer", this machine was never patented because it was immediately shared with the whole scientific community, and dozens of machines were supplied to scientists all over the world) 1976, Heuser
3 Using the "quick-freeze" machine, obtained the first-ever electron microscopic pictures of how nerves communicate with each other on the millisecond timescale (which they do by "exocytotic" secretion of neuro-chemical transmitters). 1978, Heuser
4 Created the first method for obtaining truly high-resolution, three-dimensional electron microscopic pictures of whole cells (the "deep-etch" method, designed to be used exclusively with cells preserved by the "quick-freeze" machine). 1980, Heuser
5 Using the "quick-freeze, deep-etch" method, obtained the first-ever electron microscopic images of force-generation by a biological molecular motor (the "dynein-arm powerstroke" of cilia and flagella). 1984, Heuser
6 Developed the first method for "time-lapse" TV-viewing of the actual movements of organelles inside living cells. 1989, Heuser
7 Coined the term “nanobiology”.
1991, Kusumi
8 Performed the world’s first single fluorescent-molecule imaging in water. 1993, Harada
9 Derived the first-ever theoretical formula for confined diffusion (based on the plot of the mean-square displacement against time).
1993, Kusumi
10 Proposed a paradigm shift in the basic structure of the plasma membrane (plasma membrane partitioning/compartmentalization by actin-based membrane skeleton fence and its associated anchored-transmembrane-protein pickets). 1993, 2002, Kusumi
11 Obtained the first-ever "live" images of organizational-rearrangements within biological macromolecules (by "quick-freeze/deep-etch" electron microscopy of the acid-activation of the bacterial toxin, "VacA", and the ATP-activation of the original AAA-ATPase, "NSF"). 1995、Heuser
12 Performed the first-ever real-time observations of single fluorescent molecules on a metal surface. 1998, Harada
13 Discovered the twisting motions of DNA during transcription by RNA polymerase. 2001, Harada
14 Performed single-molecule tracking at the world’s best temporal resolution (6 microseconds, ~5,200-fold improvement). 2002, 2006, Kusumi
15 Beyond single-molecule tracking in living cells, first to observe single-molecule activation in living cells. 2004, Kusumi
16 Developed the first-ever time-resolved terahertz total internal reflection spectrometer (2004, 2007), followed by further broadening of the bandwidth (0.2 THz, 7 THz). 2009, Tanaka
17 Invented a "high-pressure" freezing machine, based on the original "quick-freeze" machine from the '70's, referred to as the "high-pressure slammer". 2004, Heuser
18 Developed the first-ever simultaneous two-color single-molecule tracking system and a method for detecting the binding of two molecules.
2005, Kusumi
19 Directly observed the binding and signal transfer of two signaling molecules in living cells, for the first time ever.
2005, Kusumi
20 Developed the first Raman microscope based on a 1.3-µm infrared laser, creating a new field of non-invasive Raman microscopy for organic and biological molecules. 2005, 2006, Tanaka
21 Patented the "high-pressure slammer"  (United States Patent No. 7,293,426; issued to John Heuser, November 13, 2007).
2007, Heuser
22 Proposed digital signal transduction, based on the results of single-molecule tracking. 2007, Kusumi
23 Developed a microscope for manipulating a single DNA chain to simultaneously measure its hardness and track single fluorescent proteins bound to the DNA chain.
2007, Harada
24 Developed the first-ever method to assess the hydration number (using terahertz spectroscopy), and determined the hydration numbers of various molecules in aqueous solutions.
2007, 2008, 2009, Tanaka
25 Developed single fluorescent-molecule tracking at the highest time resolution ever (100 microseconds; 10-fold improvement).
2008, Kusumi
26 Developed a method for generating broadband and high-power terahertz pulses from a laser with a long pulse-width, which had previously been considered impossible (2008, Tanaka).

2008, Tanaka
27 Determined for the first time ever the complex dielectric constant of the collective vibrational mode of water (6 THz). 2009, Tanaka


Co-sponsoring Companies

Carl Zeiss Microimaging Japan
Hamamatsu Photonics K.K.
JEOL, Ltd.
Leica Microsystems Japan
Nikon Instech Co., Ltd.
Nikon Instruments Company
Olympus Corporation
Photron Limited

Companies supporting the establishment of the CeMI

Astec Co., Ltd.
ANDOR Co., Ltd.
Chokakudo K.K.
Hitachi Appliances, Inc.
Hitachi High-Technologies Corporation
Hitachi Koki Co., Ltd.
Kakimi Kyukodo
Kyoto Science
Masuda Medical Instrumentation Co., Ltd.
Nacalai Tesque, Inc.
Nihon Freezer Co., Ltd.
Nihon Millipore K.K.
Shimadzu Corporation
Vacuum Devices, Inc.
Wakenyaku, Co., Ltd.