Yamaguchi University

Yamaguchi University
Research Activities

Research Activities
2014 Vol.2

2014 Vol.2

Yamaguchi University Research Activities

Masaaki OKA
President

Yamaguchi University is comprised of eight faculties and ninegraduate schools. The university has its origins in Yamaguchi
Kodo, a private school founded in 1815 by Ueda Hoyo, a feudal
clansman of Choshu Province; Yamaguchi University will
therefore celebrate its 200th anniversary in 2015. It is locatedin an area which had a great eﬀect on the Meiji Restoration,
Japan s period of modernization. This area was signiﬁcant for
creating a unique cultural climate which prepared the country
for the challenges of the new world. This spirit is still alive andis reﬂected in the university s philosophy A Place of Wisdom:
Discover it, Nourish it, and Realize it. Along with its focus on
education, research, and social contribution, the university aims
to contribute to the development of Yamaguchi Prefecture,
Japan, and the world.
More than ever before, the university is expected to promote
globalization, create innovations through research, and contribute to the revitalization of the region. The university conducts
research that exhibits its strength as a university boasting adiverse range of courses and cross-faculty research. Further, italso recognizes that research activities require international
networking and cooperation.
The brochure Yamaguchi University Research Activities
has been issued for the purpose of introducing the university s
remarkable research activities at home and abroad. I hope that
this brochure will promote cooperation among researchers andenhance interest among potential students in studying at Yamaguchi University.

Individual researchand interdisciplinary collaboration
The research vision and strategic research initiatives of Yamaguchi University
Yamaguchi University has some strategic initiatives to promote interdisciplinary research activities. One of these is the Core Clusters for Research Initiatives of Yamaguchi University , where
several groups conduct research in priority areas designated by the university. Through thisproject, teams of researchers expand their research communities and advance interdisciplinary
research, starting from basic research to applied research and then to commercialization. 21
research groups in the ﬁve priority research areas are participating at present.
The Research Institute for Time Studies at Yamaguchi University was established in 2000. The
objective of the Institute is to establish time studies as a new interdisciplinary research area
through understanding diﬀerent ﬁelds of studies from the viewpoint of time, and to present researchﬁndings to the public. It is the only institute for time studies, pursuing research through integrating
the humanities and sciences. Through diverse activities, the Research Institute for Time Studies
aims to become an international center of time studies through presenting its ﬁndings to the world.
Yamaguchi University advances the promotion of all research activities of the university throughthese strategic initiatives. It aims to establish research centers which will conduct leading research.
For this purpose, the university encourages international exchange of research at home and abroad
and aims to produce world-class research ﬁndings through interdisciplinary collaboration among
researchers in specialized ﬁelds.

Hidetoshi MIIKE
Trustee（Academic Research, Academic Information）
Vice President
Director of The Organization for Research Initiatives

C o n t e n t s
Individual research and interdisciplinary collaboration ─ 1
The research vision and strategic research initiatives of Yamaguchi University

FEATUREThe Research Institute for Time Studies

The Research Institute for Time Studies ─ 2Core Clusters for Research Initiatives of Yamaguchi University
The priority research areas:１.

to develop technology that will contribute to realizing a low-carbon and sustainable society.

２.

to create innovation in the ﬁelds of life science and medicine.

Manipulating Light: Innovative Artiﬁcial Metamaterials ─ 8

３.

to contribute to the development of the history, society and culture of Yamaguchi, and also of (South)

Unraveling the secrets of microbes ─ 12

４.

Overcoming intractable disease by uncovering
the molecular mechanisms underlying the stress response ─ 14

５.

Core Clusters for Research Initiatives of Yamaguchi University［Interview］

East Asia.

Exploring hyper functional materials and devices based on metamaterials

to develop technology contributing to providing information on the environment, climate variability,
predictability, and disaster prevention etc.

Microbial evolution in function and their environmental adaptation

to integrate the humanities and sciences, leading to the future and the 200th anniversary of Yamaguchi
University.

New approaches to understand and treat stress-related diseases

1T h e R e s e a rc h I n s t i t u t e f o r
T im e St udies
山口大学

Yamaguchi University Research Activities

The Research Institute for Time Studies

FEATURE

時間学研究所Interview with Prof. Shoichi Kai, Director of The Research Institute for Time Studies
Comments on expectations for the development of RITSTOPICS

Prof. Kai met Dr. Heisuke Hironaka

COLUMNTime and Free Will

Introduction to Research
REPORT

The mysterious "Cutaneous Rabbit” illusion –Postdiction–

RITS held an academic symposium in Fukuoka

Introduction to Research

Findings related to the biological clock

Information on The Research Institute for Time Studies

Interview with Prof. Shoichi Kai,
Director of The Research Institute for Time Studies
You became the director of The Research Institute forTime Studies (RITS) in June 2014. Could you please tell
us your past relationship with RITS, if any?
Prof. Kai I was a guest professor of RITS for three years
from 2010 and once gave a seminar at RITS in somerelation with time studies. The title of my seminar at thattime was something like Rhythm and Noise , in which I
discussed how noises are related to the formation of
periodic rhythms and I also showed that they play arather positive role in this formation. Such a role of noises
was a new ﬁnding and unexpected. Another occasion was
maybe around 5 years ago when I gave a lecture at RITS
as an invited speaker at the annual meeting of the Japan
Society of Time Studies. Though I don t remember thetitle and content of the talk anymore, I think it was
related to pattern formation.

Shoichi KAI

Director of The Research Institute for Time Studies
Professor Kai received his PhD degree from Kyushu University in 1977.

Photos below are posters of symposiums and seminars held by RITS

Since then he worked at Kyushu University as a research associate
We have heard that you conduct research in various(Department of Electronics), at Stanford University as a postdoc
ﬁelds. What is your research as your life work?
(Department of Chemistry from 1979 to 1981), at Kyushu Institute ofTechnology as an associate professor and later full professor ofProf. Kai My research has been in physics in nonlinear
Electrical Engineering. From 1994 he was a professor of Applied Physics
dynamics and complex materials over for 40 years. Muchat Kyushu University and retired in 2012 (Professor emeritus of Kyushu
University).
of my research has focused on fundamental studies toclarify the mechanism of pattern formation in various
nonlinear systems. I conduct research on both non-living and living systems, e.g. ﬂuids, crystals, polymers, liquid
crystals, chemical reactions, brains, bacteria and plants. If I gave you keywords about my work, they would becomplex physics, electro-convection, turbulence, chaotic behavior and oscillations, that is, chaotic and regularstructures in space and time. My goal was then to ﬁnd the formation principle and formation universality for such
structures as fundamental physics in systems far from thermal equilibrium. Unfortunately I could not successfully
achieve my goal before my retirement because too many diﬃcult problems were involved.

Comments on expectations for the development of RITS
Hidetoshi MIIKE, Vice President of Yamaguchi University
Dr. Heisuke Hironaka hoped to develop a unique research ﬁeld at Yamaguchi University when he
was the president (1996-2002). At that time, an active research group in the ﬁeld of ʻchronobiologyʼ
of Yamaguchi University was one of the world leaders in the ﬁeld. Then Dr. Hironaka decided tostart the new area of research ʻtime studiesʼ by integrating the humanities and sciences, and The
Research Institute for Time Studies was established in 2000.
Currently, lots of research related to time studies is being conducted at RITS by researchers of
RITS and many guest researchers. International symposiums and seminars are held regularly by
RITS in order to present research ﬁndings and to familiarize the public with time studies.
I think it is important for the expansion of RITS and time studies to steadily let people know about
our research activities. This will increase the number of fellow researchers wishing to participate.
I expect RITS will become a core research center and many top level researchers of the world will
come to research at RITS.

2

3

FEATURE

Yamaguchi University Research Activities

The Research Institute for Time Studies

Assoc. Prof. Takuo Aoyama joined
the RITS as a lecturer in 2006. He
was appointed as an associate
professor since December 2009. He
was awarded the Ishimoto Prize of
the Philosophy of Science Society
Japan in 2006

COLUMNTime and Free Will Takuo AOYAMA
What is the relation between your research and Time Studies?
Prof. KAI When I was a guest professor of RITS, I noticed, from the viewpoint of interdisciplinary science basedon nonlinear dynamics, that Time Studies was very similar to Complex Physics and Sciences . I would say now
both almost overlap each other and must have the same goal.

My philosophical research interests are time, language, freedom and the mind-body

As the director of RITS, what is your opinion of Time Studies now and what does the future hold for Time
Studies?
Prof. Kai The ﬁeld Time Studies is not yet well established and it is in a similar situation to Complex Sciences
some years ago. The word Complex Sciences was born in the 90s, i.e. already more than 20 years ago. At the
beginning, research ﬁelds covered by Complex Sciences were not completely established, and neither was its
meaning. But now most scientists understand what it is and how broad. As Time Studies is younger than that,it has not yet reached such a level and it is still localized in narrower and more individual ﬁelds. Knowing thecurrent development of the ﬁeld Complex Sciences , however, I am quite sure that it has a great opportunity,
perspective and possibility for future development.

movement of hands is determined by the brain activity prior to the conscious will toPlease tell us your expectations and goals for the future of RITS.
Prof. Kai At ﬁrst I expect that researchers from broad ﬁelds, such as mathematics, physics, chemistry, biology,
medicine, economics, sociology, philosophy, the humanities, literature and so on, would participate together andexchange ideas on time studies at RITS as a unique center. The most important role of RITS is not to make cooperative research in similar ﬁelds but rather to encourage theexchange of fresh ideas from researchers to researchersamong quite diﬀerent ﬁelds, that is, the creation of intellectual
capacity and knowledge. We should not require short term
output but long term incubation and ripening of ideas as wellas collaboration. As a result the ﬁeld Time Studies will beestablished as a really interdisciplinary science. After that, I
wish, it will spread out from RITS to all over the world. Thisis currently my dream and, I guess, would be also an aim ofProfessor Emeritus Heisuke Hironaka who is the founder of
RITS, a former President of Yamaguchi University and a
Fields Prize winner as well.

relationship. More recently, I have been thinking about the problem of time and freewill, a problem that concerns both the humanities and sciences. For example, arecent introductory book* explains clearly how the progress of neuroscience andsocial psychology aﬀects our understanding of free will. Assume that the voluntary
move. (Some scientiﬁc data partly support this hypothesis.) In that case, can we say
the movement is caused by free will? If so, how should we deﬁne free will ? These
questions are not mere intellectual speculation, but they are tightly connected to our
ethical practice in assigning responsibility. I would like to continue researching these
topics and reporting the results to society, mainly from the viewpoint of time studies.
* A. R. Mele (2013) A Dialogue on Free Will and Science

Introduction to Research

Lectures on
Analytic Philosophy
Takuo Aoyama (2012)
Chikumashobo Ltd.

The Philosophy ofTime Travel(New Edition)
Takuo Aoyama (2011)
Chikumashobo Ltd.

The mysterious "Cutaneous Rabbit illusion ‒Postdiction‒

Prof. Makoto Miyazaki of RITS uses psychological and neurophysiologicalapproaches to investigate the mechanisms of the brain s information processing.
Sensory illusions provide clues for such mechanisms. One well-known sensory
illusion is called the cutaneous rabbit, where one feels as if a small rabbit ishopping along the skin (Fig.1). When physical stimuli are presented in rapid
succession, the second and third stimulations are perceived to occur not at the actual
location of the stimulations, but at locations closer to each other, as shown in orange
in Figure 1. It was reported that the region corresponding to the points of perceived
cutaneous illusion is activated in the somatotopic map of the brain. This is the resultof Stimulus 3, which occurs later, retroactively inﬂuencing the perception of Stimulus
2 that has already occurred; this is a very mysterious phenomenon as it appears tocontradict our established views of the physical world. This eﬀect demonstrates what
has been termed as postdiction and is attracting widespread attention.
Prof. Miyazaki s recent studies have shown that the cutaneous rabbit is felt not only on one s skin, but is also perceived along an
external object that is being held in one s hand (Fig.2). This suggests that the brain processes the external object as part of the body.
Application of this theory to the development of instruments such as prostheses is eagerly anticipated.

Figure 1:
Stimuli triggering cutaneous rabbit
Stimulus 1, 2
(0.8s interval)

TOPICS

Stimulus 3(<0.1s after Stimulus 2)Prof. Kai met Dr. Heisuke Hironaka
Prof. Kai had a meeting with Director Emeritus Dr. Heisuke Hironaka, former president of theuniversity. Dr. Hironaka said that in his opinion, there were few opportunities for interdisciplinary exchange when he was the president, and that he had felt the importance of such opportunities was not being recognized in Japan, to judge from his experiences at institutes abroadsuch as Harvard University. Therefore, his goal was to create opportunities for discussions
beyond research ﬁelds in the university, and in this way, he decided to establish the RITS. Dr.
Hironaka emphasized that it is important for researchers to express their technical knowledge
simply to others in order to communicate smoothly, and also to listen to researchers of
diﬀerent ﬁelds in order to understand some fundamental concepts relating to their own
research areas. (June 24, 2014)
Dr. Heisuke Hironaka is a mathematician. He was bone in 1931 in Yamaguchi prefecture. He received his Ph.D.
in 1960 from Harvard University. He was awarded the Fields Medal in 1970. He was a president of Yamaguchi
University (1996-2002).

4

Figure 2:
Sensory perception felt on an external object
Stimulus
1, 2
Stimulus3, 
   ms after)(800msinterval)(50 or80ms
Stimulus 2)

Actual stimulation

The “Cutaneous Rabbit” Hopping out of the Body
Miyazaki et al. J Neurosci Science 30(5):1856-1860, 2010

Perceived stimulation

Dr. Heisuke Hironaka

Sensory illusion of three distinct locations being
stimulated in sequence5

Yamaguchi University Research Activities

The Research Institute for Time Studies

FEATUREThe Research Institute for Time Studies

TOPICSThe Research Institute for Time Studies (RITS) at Yamaguchi University was established in April 2000 when Dr. Heisuke

RITS held an academic symposium in Fukuoka

Hironaka was the president of the university. The aim is to create Time Studies as a new interdisciplinary area of study by

RITS held an academic symposium titled Possible application of the internal clock to learning, exercise andbusiness co-organized by the Japanese Society for Time Studies in Fukuoka Prefecture on June 7.
Prof. Makoto Akashi of RITS gave an outline of the mechanism of the biological clock and explained how health risksarise from the ways in which the biological clocks of modern humans are not attuned to natural rhythms.
Fuminori Ono, who is an Associate Professor in the Faculty of Education at Yamaguchi University, reported ﬁndings
showing that we perceive length of time by the rhythm of the day.
Researchers from other universities and laboratories also presented research results related to the biological clock.
An active discussion about the surprising relationships between fundamental abilities and human health to the
biological clock followed, with questions posed and opinions expressed about modern society, where natural rhythms
are not emphasized.
This symposium is held every year on a date close to June 10, Time Day , and topics related to time are discussed.

understanding nature, human, society, and culture from the viewpoint of time, and for society to beneﬁt from the research
results. The activities of RITS provided an important opportunity for the establishment of the Japanese Society for Time
Studies.
RITS is composed of the director, researchers, and administrative staﬀ. About 100 researchers on campus and outside of
Yamaguchi University are involved in RITS activities in various ways.
The lectures include topics on time-related areas such as developmental biology, evolution, the birth of the universe, andsociological time. In particular, students are required to understand the interaction between social time and biological time, andto consider the signiﬁcance and issues of time in human life.
The research organization of RITS consists of four study groups. The researchers work in a wide range of ﬁelds related to timestudies such as biology, medicine, sociology, philosophy, literature, geology, psychology, economics, and social anthropology.

URL: http://www.rits.yamaguchi-u.ac.jp/

Director

Shoichi KAI (Director of the Research Institute for Time Studies)

Researchers（Full-Time Teaching Staﬀ）
Kenta FUJISAWA (Professor of the Research Institute for Time Studies)
Specialty：Radio astronomy, space physics
Makoto MIYAZAKI (Professor of the Research Institute for Time Studies)

LeaﬂetSpecialty：Cognitive neuroscience, sports science
Prof. Makoto Akashi

Makoto AKASHI (Professor of the Research Institute for Time Studies)
Specialty：Chronobiology, molecular biology, cell biology, time medicine
Takuo AOYAMA (Associate professor of the Research Institute for Time Studies)
Specialty：Philosophy, ethics
Hiroki MIGITA (Lecturer of the Research Institute for Time Studies)
Specialty： Sociology (theory of celebration, history of mentalities)
Miho SATO (Research associate of the Research Institute for Time Studies)

Introduction to ResearchSpecialty：Chronobiology, Molecular biology

Findings related to the biological clock

The research results of Akaishi laboratory are shown on the online Cell Reports journal which is
published by Cell Press on May 1 (paper 1) and July 10 (paper2) in 2014.

(paper 1)
In the current model of the mammalian circadian clock, PERIOD represses the activity of the circadian transcription factors, either
independently or together with CRYPTOCHROME. The authors provided evidence that PERIOD has an entirely diﬀerent function fromthat reported previously. Overall, the results support the hypothesis that PERIOD plays diﬀerent roles in diﬀerent circadian phases: anearly phase in which it suppresses CRYPTOCHROME activity, and a later phase in which it acts as a transcriptional repressor withCRYPTOCHROME. This buﬀering eﬀect of PERIOD might help to prolong the period of rhythmic gene expression. These researchﬁndings contribute the development of chronobiology.
(paper2)
The circadian clock is entrained to environmental cycles by external cue-mediated phaseadjustment. However the mechanism of feeding-induced phase resetting remains unclear.
The authors report that insulin may be involved in feeding-induced tissue-type-dependent
entrainment. In the experiments, insulin-induced phase shift in peripheral clocks wasdependent on tissue type, which was consistent with tissue-speciﬁc insulin sensitivity,and peripheral entrainment in insulin-sensitive tissues involved the signaling pathways.
These results suggest that insulin may be an immediate early factor in feeding-mediatedtissue-speciﬁc entrainment. These research ﬁndings are expected to be the ﬁrst step inresolving the entire control mechanism of the circadian clock.
(paper 1) Akashi M, Okamoto A, Tsuchiya Y, Todo T, Nishida E, Node K. A Positive Role for PERIOD in Mammalian Circadian Gene Expression. Cell Reports 7(4):1056-1064, 2014
(paper2) Sato M, Murakami M, Node K, Matsumura R, Akash M. The Role of the Endocrine System in Feeding-Induced Tissue-Speciﬁc Circadian Entrainment. Cell Reports ,Published online (July 10, 2014), DOI:10.1016/j.celrep.2014.06.0l5

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Web siteGroup 1

Fields Related to the Harmony of Social Time and Human TimeIn modern society, as a result of the arrival of the global information society, the tension between social time and human time
has become intense. The aim of this study group is to harmonize social time and human time through the scientiﬁc research ofthese time categories.

Group 2

Fields Related to Biological Time, Evolution and Environmental Change

The research members are studying to understand how environmental changes and biological evolution interact with each otherthroughout the never-ending and everlasting time. The goal of the research is to elucidate what time is for organisms byobtaining experimental data using various organisms ranging from protozoa to mice.

Group 3

Fields Related to Representations of Time in Multicultural Areas

The question of how to represent time is closely related to cultures and organizations. We examine the diﬀerence ofrepresentations of time in multicultural areas from the perspective of thought, literature, linguistics, and so on. In addition, westudy the conceptual base of time from philosophy and time-related arts.

Group 4

Various Fields in Time Studies

Time is an important concept in a variety of study ﬁelds. The concept of time is slightly diﬀerent in each study ﬁeld. In thisstudy group, time is considered from many diﬀerent perspectives in ﬁelds such as medicine, agriculture, physics, andengineering, and the possibilities of time studies are investigated.

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Core Clusters for
Research Initiatives

Yamaguchi University Research Activities

Exploring hyper functional materials and devices based on metamaterials

are referred to as left-handed materials. Left-handed materials havegained great attention because they have unusual negative refractive
indices: when light strikes a left-handed material, the ray of the lightbends with a negative angle of refraction, in the opposite direction tothat which occurs with a normal material (Fig. 1). The ﬁrst
demonstration of left-handed metamaterial suﬀered from inevitablenarrow band and high loss characteristics due to the intrinsic
resonant nature of its constituents. Therefore, I took a diﬀerent
approach and proposed a new theory based on the transmission line
approach of circuit theory. Luckily, I succeeded in experimental
veriﬁcations of the theory with a novel left-handed metamaterial
with an extremely wide band and low loss characteristics. A numberof novel, epoch-making devices and antennas with extreme
characteristics have been developed at microwave frequency regions
so far, based on my theory.

Invisible cloak for real?

［Interview］

Manipulating Light:
Innovative Artiﬁcial Metamaterials
Metamaterials might not be a commonly used terminology now; however they canpotentially change future daily life by opening up an unusual and new side of the world wehave never experienced. Since the possibility of the realization of metamaterials was
suggested at the beginning of this century, metamaterials have fascinated many physicists,scientists and engineers. Prof. Atsushi Sanada, a leading scientist in the ﬁeld, speaks about
the potential and future of metamaterials.

Atsushi
SANADA
Professor
Graduate School of
Science and Engineering

Prof. Atsushi Sanada received his B.E. in 1989 and
his Ph.D. in Engineering in 1994 from Okayama
University. He joined Yamaguchi University as an
assistant, and became a professor of Graduate
School of Science and Engineering in 2001.He
studied in outer institutes several times as a guest
researcher, in 1994-95 and 2002-03 at UCLA, in
2005-06 at ATR. In 2005, he was a special
researcher in the NHK science & technology researchlaboratory as well. Currently, he is the Coordinator ofIEEE MTT-S AdCom Region 10(Asia-Paciﬁc).

What is Left-handed metamaterial ?
−First of all, tell us about the metamateirals you are working on.
Brieﬂy, what are metamaterials?
Prof. Sanada Brieﬂy speaking, metamaterials are artiﬁciallystructured materials consisting of anarray of small sub-wavelength pieces ofmaterial that mimic natural atoms or
molecules. They possess unusualelectromagnetic properties that natural
materials never exhibit, like an invisible
cloak in science ﬁction movies or
Left-handed metamaterial realization
animations ﬁlms, for instance.
with negative refractive indices−When did you start working on metamaterial research?
Prof. Sanada At the end of the 90s. I was working on
magneto-electric eﬀects of metals, magnetic materials,
superconducting materials, and the like at the end of the 90 s at YU.

8

It had been known that the magneto-electric eﬀect can be enhanced
by combining materials of diﬀerent kinds, and I was trying to realize
novel materials with enhanced magneto-electric properties based on
the artiﬁcial material concept. In 2002, my research proposal was
accepted by the Ministry of Education, Culture, Sports, Science andTechnology of Japan and I decided to go to UCLA to proceed to theresearch area of metamaterials.
In the US, a DARPA program on metamaterials had just beenlaunched at that time and the lab I joined was involved. The main
topic in the program was physics, theory, and applications ofleft-handed metamaterials, so I focused on the subject at the moment.
Left-handed materials are materials with simultaneous negative
permittivity and negative permeability and this leads to negativerefractive indices. In left-handed materials, the electric ﬁeld vector E,
the magnetic ﬁeld vector H, and the wavenumber vector k of light orelectromagnetic waves form a left-handed triplet. That is why they

■ Figure 1 Law of refraction n1sinθ1=n2sinθ2
natural material

Left-handed metamaterial−You mentioned that an invisible cloak could be realized bymetamaterials, but how does it work?
Prof. Sanada When you see something, say an object for instance,
your eyes are detecting rays of light shone, reﬂected, or scattered by
the object. If you have another obstacle just between you and theobject, the rays of lights are obstructed and cannot reach you,resulting in the object becoming invisible. In this case, you see the
obstacle instead of the object. Suppose we can bend the rays of lightand make a detour for the rays around the obstacle, you will again
be able to see the object. In this case, the obstacle looks transparent
and disappears and you cannot even ﬁgure out that the obstacle
exists (Fig. 2). Invisible cloaks provide detours for the rays of light.
More speciﬁcally, invisible cloaks realize transformations ofcoordinate systems around obstacles. For instance, according toRelativity, rays of light can be bent by a space coordinatetransformation caused by gravity. This has already been conﬁrmed
by a well-known observation of light from a distant star behind
another heavy star. The invisible cloak actually performs an
operation equivalent to a space coordinate transformation.
■ Figure 2−In a Harry Potter movie or Doraemon cartoon, people put on
an invisible cloak to visually hide from others. How realistic is theinvisible cloak?
Prof. Sanada Good question. The concept of the invisible cloak has
already been demonstrated and will be operational in practicalapplications in no time, sometime within 10 years, maybe. So far, it isdemonstrated at lower frequencies, like the microwave region, andscientists are making extensive progress toward realizing it in the
optical region of visible light. Flexible and wearable cloaks may havea lot more issues to overcome but are potentially possible in thesame manner.
In addition, similar but diﬀerent camouﬂage or illusion technologies
have been demonstrated recently. For instance, let me explain an
illusion carpet technology developed in my lab. The illusion carpet
hides a bump on a ﬂoor or a mirror and you cannot see the bumpover the carpet at all. The illusion carpet consists of an array of ﬁne
metallic transmission lines, and transforms the space above thebump into a square one with a ﬂat ﬂoor. Therefore, light waves
refracted or diﬀracted by the transformed space can appear exactly
the same as those refracted or diﬀracted by the ﬂat ﬂoor and one
cannot see the bump at all (Fig. 3).
■ Figure 3

Theory of illusion carpets

（a）

（ｂ）

（ｃ）

Theory of invisible cloaks

A bird can be seen in front of the tree.
reﬂected lights（a）Reﬂection from ﬂat ﬂoor（b）Reﬂected light scattered by a bump（c）Reﬂection observed as if without bump

When covered by an invisible cloak,
the bird is no longer visible and thewhole tree can be seen instead.

an invisible cloak(Drawing based on material provided by National
Institute of Science and Technology Policy)

Technically speaking, the structure fully controls all the componentsof permittivity and permeability tensors, and the challenge here is
how to realize it by a structured artiﬁcial material, which is the main
subject of this research and is gaining attention from all over theworld. We have established a rigorous method to design cloak
materials. More speciﬁcally, in order to realize a cloak material, ﬁrst
the cloak space is transformed into an appropriate coordinate system
to accommodate the shape to be hidden, and equivalent material
parameters are determined. Then, the space is discretized into small
subwavelength areas, and the structural parameters in each of thediscretized areas are computed to realize the material tensor
parameters. As a result, cloak structures can be systematicallydesigned to meet speciﬁcations. So far, the cloak design has been
totally empirical and not straightforward. Our approach is the ﬁrst
practical solution for this complicated problem.
(Refer to the Coordinate Transformation.)

9

Core Clusters for
Research Initiatives

Yamaguchi University Research Activities

Exploring hyper functional materials and devices based on metamaterials

Realizing unusual devices and materials

Explanation: The coordinate transformation−You have many computers in your lab, don't you?
Prof. Sanada Yes. They are mostly for full-wave electromagnetic
simulations of metamaterial designs. For instance, in the carpet/cloak
design, dimensions of the small metallic constituents are determinedby solving Maxwell's equations with huge combinations of structuralparameters based upon our theory. Luckily, we have strong support
from some software venders, and selections of simulation tools basedon various kinds of numerical techniques are available in the lab.

bunch of Computers

A coordinate transformation is a conversion from one system toanother, to describe the same space.
A single point P(x, y) on one coordinate is projected onto P (x ,y ) on the other coordinate system,(See Fig. T-1(a)). Generally, both of the original and transformed
coordinates may not be the rectangular coordinates where thebasis e1, e2 cross orthogonally (Orthonormal coordinate).
When Maxwell s equation is satisﬁed beyond the conversion, therays of light will trace corresponding points on both coordinates.
If a circle of radius b, which is shown in Fig. T-1(b), is projected
onto a donut-like region with inner diameter a and outer diameterb as shown in Fig. T-1(c),and if Maxwell s equation is satisﬁed after the transformation, theray of light shown as the yellow line in Fig. T-1(b) will bend byfollowing the yellow line in the transformed coordinate Fig. T-1(c).
In this case, the inner area of the circle of radius a (0<r <a) in
Fig. T-1(c) does not have a corresponding area in Fig. T-1(b).
Therefore, no reﬂection and scattering of electromagnetic wave
appears. This means an object in this area becomes invisible.
The invisible cloak can be realized by placing heterogeneous
anisotropic materials (i.e. metamaterials) in the donut-like orange
colored area of a<r <b in Fig. T-1(d).

−The room looks highly equipped.
Prof. Sanada Indeed. We have introduced quite unique material
measurement systems and nano-fabrication systems supported by
the university and the government. We can evaluate diverse
properties of natural and artiﬁcial materials in a wide range up to
Terahertz frequency regions in the lab. Some of the products are
the ﬁrst ones of their kind or our in-house products developedwith enormous support from other institutes and companies, andare very powerful and unique.

■ Figure 4

A model of an illusion carpet

radio wave darkroom−You travel a lot in the world.
Prof. Sanada Because I have to. I frequently go abroad not only for
lectures and invited talks in conferences or meetings but also forvolunteer eﬀorts in the academic community. I often travel abroadwith my students to help nurture young researchers' ambitions andsense of globalization.
−What do you teach your students in the lab other than research?

In this illusion carpet, tiny swastika metal pieces are placed at precisely
calculated locations.

Prof. Sanada I expect students to have a wide perspective and to
network with others across disciplines. Many of my students get jobs
at companies or institutes in the electronics or communicationindustries, yet I believe networking helps a lot in the rest of theirlife.
−How do you picture the future of your research area?
Prof. Sanada We can easily imagine that future research topics
will rely heavily on a combination of multiple technologies withresearchers in multiple areas. For instance, metamaterial science
covers material and device science, electronics, computational
science, mechanical and nano-fabrication technologies, chemical
science, bio-science and technologies as well as electromagnetics andphysics. Exploiting synergic factors would be of more importance.

Core Clusters for Research Initiatives

Research Area: to develop technology that will contribute to realizing
a low-carbon and sustainable society.

Exploring hyper functional materials anddevices based on metamaterials−Finally, tell us about your dreams.

This research initiative aims to establish basic theories forProf. Sanada I will concentrate on realizing cloaks of invisibility
and illusions in the near future, hoping to see the technology becomecommon in our daily life.

super-functional artiﬁcial materials which have speciﬁc（Interviewed by Masataka Nikaido, URA）

Evaluation and monitoring of the materials, large scale

physical properties and the fundamental technologies todesign, fabricate and evaluate those artiﬁcial materials.
simulation, design of waveguides/devices, nano-fabrication,material measurement systems

10

and chemistry-based fabrication technologies are promoted
by a network of six researchers with Dr. Sanada s leadership.

Physics Chemistry

Physicalphenomena
AtomMaterial design
Modeling

Designtechnology

Molecule

Material

Deviceengineering

Creationprocessing
technology

Core Clusters for
Research Initiatives
Metamaterials

Evaluation
technology

Systems
engineering

Ultra-functional
materials anddevices creation

11

Core Clusters for
Research Initiatives

Yamaguchi University Research Activities

Microbial evolution in function and their environmental adaptation

Unraveling the secrets of microbes

Rediscovering Paramecium as a bioresource

The world around us is ﬁlled with microbes that cannot be detected by the naked eye. Microbiologists have been studying microbes from
diﬀerent perspectives, including technology, ecology, and pathology. What will happen when these diﬀerent approaches loosely collaborate?

Sharing common interests in target microbes
Nowadays where research disciplines and methods have been highly
segmented, researchers require various motivations to form alliances,including launching large-scale projects, furthering research,increasing eﬃciency by dividing tasks, and brainstorming ideas
through interaction between diﬀerent research ﬁelds. In the ﬁeld oflife sciences, sharing a common interest in target microbes could be
added to the list. The Core Clusters for Research Initiatives
Microbial evolution in function and their environmental adaptationgroup was originally founded in 2005 and is a loose-knit communityof researchers who actively participate in research exchanges. A
total of 32 researchers studying viruses, bacteria, fungi, and protozoa,
come together from various departments, including medicine,science, agriculture, engineering, and veterinary medicine.
Just as the word microbes encompasses a broad spectrum of
species, there is a wide range of research targets for this initiative(Photo 1). The research topics are very extensive, ranging from basic
science to applied science, for example from trying to discovervarious aspects of the phenomenon of life by understanding
microbial life, trying to exploit microbes abilities for industrial
applications, to ﬁghting microbial infections in both humans andplants. So what draws them together? It is their interest in microbes
and the universality that is evident through their research. Figure 1
shows the processes of Holospora infection in Paramecium cells, andListeria infection in mammalian cells. In comparison, there are
surprising degrees of commonality including the host uptake process
through endocytosis, and the invasion into host cytoplasm mediatedby cell membrane-surface protein interactions. The unique nature of
the respective research targets and the universality of the microbesthat sometimes presents itself are an integral part of what makes
this research fascinating, and the academic conference held annuallyat Yamaguchi University allows researchers to share theirfascinations and interests. From the breadth of the initiative s
diverse research activities, we take this opportunity to share theresearches on Paramecium and heat-resistant fermentation.

■ Photo 1: Various microbes as research materials

Cyanidioschyzon merolae

Kluyveromyces marxianus

Saccharomyces cerevisiae

（a）

to

cell

Professor
Graduate School of Scienceand Engineering

Holospora obtusa

Macronucleus

DV-IV

Cytopharynx
EscapeEndocytosis

Research Area: to create innovation in the ﬁeldsof life science and medicine（b）

to Mammalian Cell
Listeria monocytogenes

Ec

Escherichia coli

Endocytosis

Lysosome

×

MRC1

Heat-resistant microbes: promoting new concepts
and returning research results to society
Achieving unprecedented research results and establishing newconcepts in academia is one of researcher s dreams. The researchgroup headed by Professor Mamoru Yamada is promoting the conceptof thermotolerant microbes, whereby microbes that are traditionallyused in fermentation industries are modiﬁed so that their optimal
fermentation temperatures shift 10 to 20 °C upward. Using cutting-edge
technologies in genomics and metabolomics, the research group isstarting to acquire evidence that supports their concept. In theheat-resistant ethanol fermentation project Prof. Yamada is currently
working on, heat-resistant yeast is collected from natural environments
in collaboration with Southeast Asian research institutions in Thailand,Laos, and Vietnam, and improved using selective breeding. Prof.
Yamada is also collaborating with researchers from the Department ofEngineering to design fermentation systems at thermotolerant
temperature ranges. Collaborations are not limited to academia, but also
extend to commercial industries to promote fermentation industry intropical regions where such industrial infrastructure is relatively weak.
As the Convention on Biological Diversity aﬀects the academic
research, international cooperation in the search and utilization ofnatural resources is highly sought after. Prof. Yamada s eﬀorts informing academic collaborations and returning research results tosociety is receiving attention as a case model for research expansion.
(Reported by Yuki Tonooka, URA)

Lysosome

DelayedfusionLysosome

The purpose of this project is to systematically collect, preserveand provide bioresources such as experimental animals, plants
and microbes that are important for the nation to strategicallyorganize. Research institutions with advanced infrastructuresand resources are chosen as core facilities to carry out
collection, preservation, and provision of bioresources.

Ec

Lm

Lm

DV-I

Digestion

FusionPhagosome

FusionDigestion

AcPase activity (-)

AcPase activity (+)

DV-II

Research Groups

Growth and escape

TOPICS

Microbial evolution in function and their environmental adaptation

Functional analysis of microbes

In this initiative, diﬀerent microbial research groups within Yamaguchi University that are investigating
fermenting microbes, parasitic and symbiotic microbes, and environmental microbes, come together toform an integrated inter-departmental microbial research group. It consists of three research groups.
Each research group shares their cutting-edge technologies through workshops within the research
initiative, and with other young researchers at Yamaguchi University and in Southeast Asia. In the
research conference held annually in December, more than 150 researchers attend and over 100
research projects are presented every year. In addition, this research initiative actively collaborates
and interacts with research institutions outside of Yamaguchi University, as well as private industries.

Parasitism, symbiosis and environmental adaptation of microbes
Maintenance and repair of the ecosystem by microbes

Collaborating institutions〇International and domestic aﬃliated universities〇Neighboring universities, research institutions and museums etc.
〇Domestic corporations
http://accafe.jp/microorganisms_yu/

12Masahiro
FUJISHIMA

Paramecium caudatum■ Figure 1: Comparison between the infection processesof bacteria to eukaryotic cells

DV-III

Core Clusters for Research Initiatives

Colletotrichum gloeosporioides

Paramecium is a ciliated protozoon commonly found near humanliving spheres such as in ponds, sewers and irrigation channels. Theircell size is large, ranging from 100 to 250 µm, they possesscharacteristic organelles such as cilia, contractile vacuole,macronucleus, and micronucleus. They have been widely used as amodel organism in cell biology. Furthermore, there is a large body ofresearch into their morphology, reproduction, and behavior, and they
have a long history of being used as research material in the study ofgenetics. For example, the fact that we can easily distinguish most
mutations of paramecia under the microscope is a characteristic notfound in other microbes. Recently Paramecium has been chosen as
part of the National BioResource Project* by Ministry of Education,
Culture, Sports, Science and Technology of Japan, and Prof. Masahiro
Fujishima is serving as the center representative. This project
maintains Paramecium resources of international standards andprovides any researchers who have an interest in Paramecium with
their desired strains. Collections of strains donated by researchers or
sampled from the nature are maintained in a database along with thesampling location, and genetic and morphological characteristics.
Strains used for genome and transcriptome studies, progeny fromthe cross in the laboratories and mutant strains are also available. In

addition, strains which have endosymbiotic bacteria or algae andmonoclonal antibodies (mAbs) for both host Paramecium and their
symbionts developed through the research are also available.

MamoruYAMADA

Professor
Graduate School of
Medicine (Agriculture)

The initiative welcomes a new researcher specializing in soil chemistry

In December 2013, Assistant Prof. Yukiko Yanagi from the Department of Agriculture, who specializes in soil chemistry,joined this research initiative. While soil organic matter is the largest reservoir of carbon in terrestrial ecosystems, thedecomposition process of humic substances, the main constituent of soil, is not fully understood. Assistant Prof. Yanagi
has conducted research into the biodegradation of humic substances using microbes and enzymes, and has
demonstrated that biodegradability depends on the speciﬁc characteristics of the substance, and that the abundance ofdegrading microorganisms diﬀers between soil environments. In the future, she plans to focus on enzymatic microbes inorder to study the degradation characteristics of humic substances and analyze the mechanisms of degradation. This
research into loose symbiosis, achieved by investigating the cycling of nutrients and biologically active substances
within the soil biome, is receiving attention as a new approach in the research initiative.

Soil investigation on the Alps in Italy

13

Core Clusters for
Research Initiatives

Yamaguchi University Research Activities

New approaches to understand and treat stress-related diseases

Overcoming intractable disease by uncovering the molecularmechanisms underlying the stress response

Melanoma cell proliferation andstress response
Melanoma cells are known to induce strong adaptive mechanisms
during the stress response to achieve greater stress tolerance, andare even able to proliferate in inferior environments. According toresearch by Prof. Nakai and colleagues, when formation of the
HSF1-RPA complex is inhibited in mice, suppressed levels ofcarcinogenesis are observed, suggesting that the HSF1-RPA complex
plays a key role in melanoma cell proliferation.

Considering homeostasis as a cellular response to stress, and uncovering molecular mechanisms to discovertreatments for cancer and other intractable diseases

Akira NAKAI
A

This research initiative consists of basic medical researchers, including Prof. Nakai, andclinical medicine researchers specializing in intractable diseases. Collaboration between
basic researchers, investigating the cellular mechanisms of the stress response throughepigenomic control (called epigenomic adaptive mechanisms ), and clinicalresearchers, investigating the pathology of intractable diseases from the perspective of
epigenomic adaptive mechanisms, is expected to greatly accelerate this research.
URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/kennkyuusuishin/Kenkyuusuishin-2.html

14

Fig.1 Heat-shock factor 1 (HSF1) alone is unable tobind to DNA organized in nucleosome structures (A),HS

E

with replication protein A (RPA) and recruiting

research institutions and is awarded to collaborative research projects (both internallywithin an institution and inter-institutionally) that are supported by the respective■ Figure. 2 Eﬀect of HSF1-RPA1 interactions
on melanoma cell proliferation

components other than histone proteins (FACT, BRG1).

B

heat-shock protein (HSP) production. Melanoma cells

Proteostatsis /Melanoma cell growthutilize this mechanism to facilitate growth.

Fig.2 Athymic nude mice were injectedsubcutaneously, in two locations in the lower back, with

BRG1

RPA2

FACT RPA1

HSF1

HMV-1 cells, where endogenous heat-shock factor 1(HSF1) was replaced with green fluorescent protein

Pol Ⅱ

HSE

1400

Consequently, proteostasis is achieved by controlling

HSP(GFP), wild-type HSF1 (hHSF1-HA), or interaction

mutants (G87S-HA, G87A-HA) (n = 8). In HMV-1 cells

HSP

Transcription ON

where HSF1-replication protein A formation was

inhibited (2, 4, 5), tumor formation was significantly

1
SCR
GFP

2

3

4

5

HSF1KD1 HSF1-KD1 HSF1-KD1 HSF1-KD1
GFP
HSF1
G87S
G87A

SCR+GFPhHSF1+KD1+GFP
hHSF1+KD1+hHSF1
hHSF1+KD1+GB7S
hHSF1+R1+GB7A

1200
1000
800
600
400

*

200
0
0

4

8

12

16

20

24

28

Days

reduced.

Research Area: to create innovation in
the ﬁelds of life science and medicine

New approaches to understand and treat stress-related diseases

Transcription OFF

but is able to bind successfully by forming a complex

RPA3

Research grants supporting the advancement of medicine in Japan. This grant is for

institutions.

HSF1

▲

Proteins consist of amino acids, strung together in a chain, and theirfunction depends on the correct folding of this chain. However,misfolding can occur due to external stress and genetic factors. In
the case of misfolding, repair mechanisms, which refold or break
down the proteins, are activated; among the most important of theseis the mechanism called the heat-shock response. When cells are
exposed to proteotoxic stress, including heat shock, a set of proteins
known as heat-shock proteins (HSP) are produced, and the correct
molecular protein structures are restored.

*Takeda Science Foundation Special Project Research

Professor
Biochemistry and Molecular Biology
Graduate School of Medicine■ Figure. 1 HSP-coding gene and HSP1-RPA complex

Heat-shock proteins:
Key factors in the heat-shock responseCore Clusters for Research Initiatives

In 2014, this research project, led by Prof. Nakai, was awarded a
research grant from the Takeda Science Foundation*. Further
research developments are eagerly anticipated.
Building on his achievements in stress response research to date,
Prof. Nakai has shifted his focus to understanding the mechanismsof epigenomic control, and is aiming to uncover the pathology ofdisorders related to epigenomic adaptive mechanisms. Since
failure of the stress response can result in dysregulation of gene
expression through reprogramming of the epigenome, which canlead to Alzheimer s disease, Parkinson s disease, cancer andother intractable diseases, Prof. Nakai is devoting his research todiscovering new therapeutic targets associated with the stressresponse.
(Reported by Kumiko Tanaka, URA)

DNA, which contains genes, exists in nucleosome structures
where DNA is wound around histone protein cores. Under normal
conditions, this prevents transcriptional regulators from binding
to the DNA. However, heat-shock factor I (HSF1) is able to bind togenes that code for HSPs to induce transcription. The mechanism
behind this seemingly puzzling phenomenon was ﬁrst discoveredby Prof. Nakai and colleagues.
HSF binds to replication protein A (RPA), which is involved in
DNA replication, to form the HSF1-RPA complex. The HSF1-RPA
complex opens the nucleosome structure by recruiting
components other than histone proteins from the DNA, thereby
allowing HSF1 to bind to genes coding for HSP (Fig. 1). This
induces the production of HSPs and activates the heat-shock
response.

Tumor size (m㎥)

The word stress is often associated with psychological factors.
However, the cells in our bodies are constantly exposed to a variety ofstressors, including extreme temperatures and low oxygen levels.
Organisms maintain homeostasis by accurately monitoring andadjusting to ever-changing internal and external environments. When
exposed to stress levels exceeding the capacity of the homeostaticmechanism, or during failures of the homeostatic mechanism itself,
stress can lead to neuronal, metabolic, cardiovascular, andimmunological disorders, and cancer.
Biochemistry and Molecular Biology of The Graduate School of
Medicine, led by Professor Akira Nakai, has consistently demonstrated
the importance of the mechanism that adjusts for elevatedtemperatures, called the heat-shock response. This universal
adaptive mechanism is one of the key processes used by livingorganisms to repair damaged proteins and is integral to human health.
In the past decade, protein homeostasis, through the heat-shock
response, has been established as a signiﬁcant mechanism forsuppressing aging and preventing age-related pathological conditions,such as neuronal disorders. A relationship between this response andthe pathogenesis and growth of cancers has also been reported.
Consequently, this mechanism is now attracting attention as a new
therapeutic target.

Aiming to overcome intractable diseases

Heat-shock factors
regulate the production of HSP▲

Heat-shock response: The key to sustaining life

TOPICS

Basic Research
Molecular Pathway and the role in cell function

Inter-disciplinary
collaboration

Clinical Research
PsychiatricdisorderNeuronal
disorderMetabolicdisorderCardiovascular ImmunologicaldisorderdisorderCancerUncovering the pathology of intractable diseases

Diagnosis
Treatment

FEBS Journal Award for Top-Cited Paper Received By
Members of the Core Clusters for Research Initiatives

Associate Prof. Mitsuaki Fujimoto and Prof. Akira Nakai, who are members of Core Clusters
for Research Initiatives, won the FEBS Journal of Top-Cited Paper Award for their review
article titled The heat shock factor family and adaptation of proteotoxic stress , published in
FEBS Journal in October, 2010. This distinction is awarded to an article that receives a highvolume of citations in the two years following its publication in FEBS Journal, and ispresented by the FEBS Journal Editorial Board. This review article details the researchhistory of the HSF gene family, its proteostatic regulation, and its role in aging andage-related pathological conditions, to which the authors greatly contributed. The award
indicates the high level of international interest in this research.

15

Yamaguchi University Research Activities

Contact

Location

Graduate Schools

URL

Graduate School of Humanities

h t t p ://www.h m t .y am ag u ch i-u .ac.jp /?lan g =en

Graduate School of Educationh t t p ://www.ed u .y am ag u ch i-u .ac.jp /en g lish

Graduate School of Economics

h t t p ://www.econ o.y am ag u ch i-u .ac.jp /g s̲e.h t m l

Graduate School of Medicine

h t t p ://d s22.cc.y am ag u ch i-u .ac.jp /˜ ig ak u b u /m ed ic/EN/inde x. c gi

Graduate School of Science and Engineeringh t t p ://www.g se.y am ag u ch i-u .ac.jp /EN/

Graduate School of Agriculture

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h t t p ://www.eas.y am ag u ch i-u .ac.jp /Graduate School of Innovation and Technology Managementh t t p ://m ot .y am ag u ch i-u .ac.jp /United Graduate School of Veterinary Scienceh t t p ://d s22.cc.y am ag u ch i-u .ac.jp /˜ ren ju /e.h t m l

The United Graduate School of Agricultural
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Tokyo
Yamaguchi

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1hr.30min to Yamaguchi Ube Airport
by airplane

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Yamaguchi
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Kogushi Campus

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Yoshida Campus

1677-1 Yoshida, Yamaguchi-shi, Yamaguchi, 753-8511

Research Institute

URL

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h t t p ://www.rit s.y am ag u ch i-u .ac.jp /?p ag e̲id =33

Graduate School of Humanities, Graduate School of Education, Graduate School of Economics, Graduate School of Medicine (Science, Agriculture), Graduate School of Science and Engineering (Science), Graduate School of Agriculture, Graduate School of East Asian Studies, United
Graduate School of Veterinary Science, The United Graduate School of Agricultural Science, Tottori University, The Research Institute forTime Studies

Kogushi Campus

Tokiwa Campus

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Science and Engineering (Medicine)

Graduate School of Medicine (Engineering), Graduate School of Scienceand Engineering (Engineering), Graduate School of Innovation and Technology Management

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YAMAGUCHI UNIVERSITY
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http://www.yamaguchi-u.ac.jp/english.html■ For Research enquiries:

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http://kenkyu.yamaguchi-u.ac.jp/index.html(Japanese)■ For International Exchange enquiries:

Yamaguchi University
Research Activities
2014 vol.2

Oﬃce for International Aﬀairs Strategy
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International Student Center
http://www.isc.yamaguchi-u.ac.jp/english/top.htm

Published by the Organization for Research Initiatives, Yamaguchi University,
February 2015
Edited by the working group for Yamaguchi University Research Activities
Reports: University Research Administrator (URA) Oﬃce.
English translation: Phlicia Sun (p5 bottom, p12-15)
Cover design and art: Associate Prof. Takeshi Kinoshita (Graduate School of
Science and Engineering), Yumie Fukuda (Kinoshita Laboratory)

Cover design and art
The pictures show some of thefamous sights of Yamaguchi
Prefecture and present its long
history and rich natural beauty.
The vivid color along the bottom
is a traditional Japanese color.

Yamaguchi University

Research Activities

2014 Vol.2