CHIBARESEARCH
Highlights of innovative andcollaborative research

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University Library/Academic Link Center

Guided by its motto “Always aim higher,” CHIBA UNIVERSITY strives to nurture
globally minded students who have broad outlooks. The university values academic
diversity and actively conducts leading-edge fundamental and applied research.
Chiba University was founded as a national university in Japan in
1949, when Chiba Normal School, established in 1874, merged with
Chiba Medical College and several other educational institutions.
Currently composed of 10 faculties and 13 graduate schools, Chiba
University is one of Japan’s largest national universities, having
about 11,000 undergraduate students, 3,500 graduate students

and 3,000 faculty members on 4 campuses located near Tokyo.
The main campus at Nishi­- Chiba occupies an area of almost
400,000 square meters (100 acres) and is conveniently locatedbetween Tokyo Station (about 40 minutes by train) and Narita
International Airport. The 850-bed University Hospital, a core
hospital for the region, is adjacent to the School of Medicine on
the lnohana campus.

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TA BLE OF CONTENTS

mes of Medicago truncatula.

Chromosomes of
Glycyrrhiza uralensis.

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8M U LT I M O DA L M E D I C A L E N G I N E E R I N GCHINESE LIQUORICE GENOME
In 2016, Kazuki Saito sequenced theentire draft genome of Chinese liquorice(Glycyrrhiza uralensis), a plant used in
traditional medicine and as a natural
sweetener. Experimental and clinicalstudies suggest that Chinese liquorice
has a wide range of pharmacologicaland protective properties.
This diagram is a circular representationof the G. uralensis chromosome (red)compared with another legume whose
FIGHTING PATHOGENSC AT
HI B ATHEIRU N I V E R SPOINTI T Y | R E S E A R C H
chromosome had beenpreviously
sequenced, Medicago truncatula (grey),
OF ENTRY including
their gene densities and genes
involved in the production ofa sweetening compound.

TOWARD IMAGE-BASEDDISEASE DIAGNOSTICSCHIR A L M ATER IA LS SCIENCE
INTER NATIONA L CENTER
Novel, high-precision imaging techniques are being used to provide
non-invasive disease diagnosis andFOR
guide future
HAtreatments
DRON ASTROPHYSICSUSING LIGHT TO ESTABLISH A
NEW FIELDMUCOSA L IMMUNOLOGY A ND
A LLERGY THER A PEUTICS

OF CHIR AL MATERIALS

Optical images are overlaid
REVE ALING HIDDEN MESSAGES
with two other forms of imaging
get a clearer picture of the
FROM THE COSMOS todiseased
tissue.

H I G H L I G H T S

10Non-invasive, precise diagnosis of
diseases using advanced medical
imaging technologies could one
day replace traditional techniques
based on biopsy and dissection.
With this prospect in mind,
researchers at the Multimodal
Medical Engineering program are
combining medical and engineeringexpertise to create novel, noninvasive imaging-based methods
for diagnosing and treating disease.
The program uses
various scanning techniques,or ‘modalities’, including
computerized tomography,
magnetic resonance imaging (MRI)and ultrasound, to analyze cellularand organ variations caused bydifferent diseases.
The program’s goal is to develop
highly precise, non-invasive imaging
methods, while boosting existing
imaging techniques to improve
resolution and enable more-detailed
tissue analysis, says program leader
Hideaki Haneishi.
“Many current diseasediagnostics, particularly for cancer,
involve highly invasive, unpleasant
procedures to clarify the type andstage of the disease,” explains
Haneishi. “We are investigating,for example, the developmentof a system to diagnose
breast cancer using very-highfrequency ultrasound.”Rather than physically samplingand dissecting lymph nodes frompotentially cancerous tissue, his

12

ONE WORLD, MANY VOICES

Despite widespread differences inlanguage, customs and cultures, theworld is becoming an increasinglyinterconnected. Creating a society
where people of all cultures,countries and backgrounds aretreated with fairness and equality
requires a global effort.

Genes involvedin the productionof the sweetening
compound,glycerryzhin.
Comparing thesegenes in two
species could
help researchers
to identify
those that haveuseful biological
functions.

CENTER FOR INNOVATIVEMICROWAVE R EMOTE SENSINGPHY TOCHEMICA L PL A NT
MOLECUL A R SCIENCES

THE NE XT WAVE IN REMOTE SENSING

Gene density in M. truncatula

UNLOCKINGTHE POTENTIAL OFWe
defi
neG.fairness
the
grey)
and
uralensisas(red).
asic element of justice,” says
PHY TOCHEMICALSo Mizushima. “We embracelues such as equality and liberty.”

16

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CH I B A U N I V E R S I T Y

Pathologic
are sliced, digreconstru
jigsa

1 1

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MULTIMODA L MEDICA L
ENGINEER ING

LAYERING THE BRAIN
Multimodal imaging techniques can offer a moredetailed insight into health and disease. In this example,
researchers at Chiba University have combined different
kinds of imaging taken of a cancer patient’s brain toassess tumor pathology.

TOWARD IMAGE-BASED DISE ASE
DIAGNOSTICS
be highlighted. This may eventuallyteam has shown that it is possible
to analyse cell characteristics oflymph nodes using ultrasound. Theirtechnique highlights metastasis
positive and negative cells in
lymph nodes, enabling rapid,
painless diagnosis.
Haneishi and his team are also
devising ways to combine datafrom two or more modalities. For
example, in 2016 they developed
an image registration method thattransforms two data sets into one
coordinated system using MRI andpathological images of brain tumors.
“If we can establish thetechnology for registering two
kinds of images, then MRI featuresthat are strongly related to thepathological features of tumors can

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allow us to diagnose using only
MRI,” says Haneishi. “Determining
the relationships between different
data sets helps us build up detailed
pictures of what is going on inside
the body, not only for diagnosis but
also to improve our understandingof disease development,” he adds

NOVEL OPTICAL PROBES
Alongside conventional imaging
techniques, the researchers arealso exploring novel optical probes.
One example involves a method
for monitoring microcirculation —the flow of red blood cells — inthe body. The probe comprises
multicolored light-emitting diodes

CHIBA STUDIES ON GLOBA L
FA IR SOCIET Y

HIGH-EFFICIENCY ENERGYCON V ER SIONFORGING A FAIRER WORLDTOWARD A ZERO -EMISSION SOCIET Y

A DIFFERENT APPROACH TO FIGHTINGCANCER

22

24

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INTEGRATED RESEARCH CENTER

MEDICA L M YCOLOGYR ESE A RCH CENTER

NEXT-GENER ATION 3 D DISPL AY
A ND ME ASUR EMENTSTEEPED IN STEM CELLSMANIPUL
ATING MICROBES FOR HUMAN
RestofHE ALTHJapan
7%

FUTURE IMAGES — MORE THAN MEETSTHE EYECA NCER EPIGENOME CENTER

14

Chiba
prefecture 21%

Other 7%

America
ON REGENERATIVE SYSTEMS
5%

Global iodine production

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Japan is the second-largest producerof iodine in the world, after Chile,accounting for close to 30% of global
production. About 75% of thisproduction takes place in Chiba
prefecture, a hook-like peninsula
on Japan’s eastern coast.

CH I B A U N I V E R S I T Y

25

30

32

20

17

15
10
5

Total production:
MEDICINE FOR
33,720IMMUNE
tons/year (2013)

R EL ATED R A R E DISE ASES

01970 VATION
1975
SOFT MOLECUL A R ACTIFOR INTELLIGENT M ATER IA LS

INNOVATIVE APPROACH OFFERS HOPEFOR INTR ACTABLE PROBLEMSCATALYZING THE FUTURE OF
SMART MATERIALS
Chile 60%

1980

CENTER
OF EXCELLENCE
1985
1990
1995
FOR END OF LIFE CA R E

2000

PUT TING THE CARE BACK INTO END - OFLIFE CARE

2005

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R E ACHI NG N E W
HOR IZONS
Welcome to the inaugural issue of Chiba Research, a new publicationthat showcases the diverse and innovative work being undertaken at
the Institute for Global Prominent Research (IGPR), Chiba University.
The institute was established in 2016, with the ambitious goalof becoming a global hub for top-class research in fields as farreaching as neutrino astronomy, the science of plant-based medicine,
three-dimensional holography, and the creation of a fair, egalitarian society.
The institute is an exciting new initiative at Chiba University. It was set
up to nurture key research projects being conducted at the universitythat are deemed to be of special significance. This issue introduces
the fifteen innovative projects currently underway at IGPR. All ofthese projects were selected by an advisory board that included
external experts.
Three of these projects have been singled out as being of top importance— Toshinori Nakayama’s work on finding unconventional vaccines thatare administered via the mouth, nose or other mucosal system throughwhich most pathogens enter the body (see page 4); Takashige Omatsu’s
research into spiral-shaped laser beams that exhibit left- and righthandedness and can be used to create helical nanostructures (see page6); and Shigeru Yoshida’s use of ghost-like elementary particles known as
neutrinos to explore the high-energy Universe (see page 8).
We trust you will become as enthusiastic as we are about this new
initiative, and we look forward to presenting the latest findings from2

CH I B A U N I V E R S I T Y© agsandrew/iStock/Getty Images Plus

these projects over the coming years.

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FORGING AHEAD WITH
CREATIVE AND ORIGINALRESEARCH
A one-day kickoff symposium provided a glimpse into the innovative researchunderway at Chiba University
A symposium at Chiba University on
14 November 2016 marked the establishmentof the Institute for Global Prominent
Research (IGPR). The gathering, attended byapproximately 300 participants, introduced
15 innovative research projects that have been
selected for the IGPR, and gave members of thedifferent projects the opportunity to interact.
“IGPR’s mission is to cultivate groups
that perform novel and original researchby strategically allocating resources topromote world-level research,” explained
Ryoji Matsumoto, vice president for research
at Chiba University. Of the 15 programs, somestrategic priority areas of research will bepromoted intensively and others have been
designated incubator programs.
The day began with an address by
Akihiro Sato from the Japanese Ministryof Education, Culture, Sports, Science andTechnology (MEXT), who encouraged
participants to pursue world-class research
at Chiba University. His talk followed with an
overview of IGPR by Chiba University President
Takeshi Tokuhisa.
In the keynote lecture, Toshio Hirano,president of the National Institutes for
Quantum and Radiological Science andTechnology (QST), drew on his previous
experience as president of Osaka University
and spoke on the importance of instituting
reforms at universities.
Two guest lecturers were invited to speak at
the launch. Immunologist Kensuke Miyake fromthe University of Tokyo shared his team’s workon the use of nucleic acids to sense molecularmechanisms in the innate immune system. And
chemist Marc Koper of Leiden University in
the Netherlands elaborated on his theoreticalanalysis of electrochemical reactions forgenerating carbon-dioxide-neutral fuels.
The gathering gave the heads of threestrategic priority research promotion programs
the opportunity to introduce their work.
Toshinori Nakayama of the Graduate School of
Medicine is exploring unconventional vaccines.
These novel vaccines would be administered,
not by injection, but via the mouth, nose

A poster session at the Institute for Global Prominent Research Kickoff Symposium gave young
researchers the chance to showcase their findings and to learn about the work others are doing indifferent fields.

or other mucosal systems. His team has
also discovered the molecular mechanisms
underlying the generation and maintenance of
immunological memory, which provides thebasis for developing vaccines.
Aya Ishihara from the International
Center for Hadron Astrophysics (ICEHAP),
Graduate School of Science, is using ghost-likeelementary particles known as neutrinos toclarify how extremely high-energy cosmic rays
are generated. ICEHAP is a key collaborator in
IceCube, the international neutrino detector
in Antarctica.
Takashige Omatsu of the Graduate Schoolof Advanced Integration Science is employing
special laser beams — dubbed optical vortices
because of their helical structures — to create
nanostructures with unique features. Just
as gloves come in pairs — a left and a righthand — so do optical vortices. This property
is known as chirality and is very important inmany areas of science.
The IGPR symposium also featured three
talks on incubator projects: Kazuki Saito on themolecular investigation of bioactive compounds
found in plants that have beneficial properties,
Hideaki Haneishi on the development ofmultimodal medical engineering to realize
precision medicine; and Josaphat Tetuko Sri
Sumantyo on innovative microwave remotesensing for disaster management.
Young and ambitious researcherspresented their findings during a one-hourposter session. “The poster session was avaluable chance for young researchers tointeract with scientists from other groups,”
said Matsumoto. “Such interaction can spawn
interdisciplinary projects.”
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IN TER NATIONA L CEN TER OF EXCELLENCE IN M UCOSA L
I M M U N O L O G Y A N D I N N OVA T I V E A L L E R G Y T H E R A P E U T I C S

FIGHTING PATHOGENSAT THEIR POINT OF ENTRY

The mucous membranes that line many of
the tracts and structures in the body are
the first lines of defense against foreign
invaders. Equipped with a powerful andhighly specialized immune system, thesemucosal sentinels protect the surfaces and, byextension, the body interior, against the threatof gastrointestinal, respiratory and sexuallytransmitted infections, as well as cancer,
allergies and more.
If these immune cells let their guard down,
pathogens such as bacteria and viruses caninvade. On the other hand, if they are overly
vigilant, hyper-reactive conditions like asthma
or autoimmune inflammatory bowel disease
can take hold.
Getting the balance right is the goal of
the International Center of Excellence inMucosal Immunology and Innovative Allergy
Therapeutics.
Launched as a joint initiative between Chiba
University and the University of California,
San Diego, in 2016, the center aims to harness
the power of the mucosal immune system
to develop the next generation of preventive
vaccines against infectious, allergic andinflammatory diseases.
Most vaccines in use today are administeredby injection. But since most infectious
agents enter the body at mucosal surfaces,
vaccinating through the nose, mouth, or someother mucosal route could provide more
protection. Since transmission often occurs atthese sites, boosting the body’s ability to blockthat transmission could stop an infection or
autoimmune reaction at its source.
“While existing injectable vaccines are able
to prevent serious conditions from developing,they are not effective enough to defend
against infection,” notes program director,
Toshinori Nakayama.
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FROM BASIC RESEARCH TO
CLINICAL APPLICATIONSBefore new treatments can be developed,
however, much more needs to be learned
about the molecular architecture of themucosal immune system. That is why theInternational Center of Excellence is focusing
on basic research while simultaneously
advancing clinical applications. It is also
strengthening ties between researchers
and industry in the hope of translating its
discoveries into therapies for patients.
To this end, Nakayama is building a robust
pipeline of talented scientists who can moveresearch findings seamlessly from the labbench to the hospital bedside.
“The research system we are creating isunprecedented,” says Nakayama, who is also
vice president of Chiba University and deanof the Graduate School of Medicine and theFaculty of Medicine.
Projects at the International Center of
Excellence fall into three categories: Hiroshi
Kiyono and Satoshi Uematsu are studying thebasic mechanisms of mucosal immunology inresponse to microbial infections and assorted
diseases; Nakayama and colleagues, including
Mark Bix, Atsushi Onodera, Motoko Kimura
and Osamu Ohara, are focusing on allergic
reactions and novel treatments that target
the mucosa; and Hiroshi Nakajima, Yoshitaka
Okamoto and Naoki Shimojo belong to theclinical research team that is developing new
vaccines and adjuvants for pathogens endemic
to Japan and around the world.
Chiba has initially committed US$2 million
over five years to this alliance. Together witha matching contribution from UC San Diego,
the project will facilitate joint research andexchanges between investigators and students
on both sides of the Pacific.

© Science Photo Library/Alamy Stock Photo

Vaccines that induce immune responses at mucosal membranesof the intestines, lungs and other organs could help prevent deadly infections

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MUCOUS MEMBRANE
IN THE AIRWAY
Mucous coat layered
with tiny hairlike cilia.

Immune cells in the
mucous membraneprotect the bodyagainst invasion bypathogens such asbacteria and viruses,
but if they are too
vigilant they cancause disease.
Vaccines that directly
target the mucosal
surface could provide
more protection than atypical injection.

Epithelium

Connective
tissueCH I B A U N I V E R S I T Y

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CHIR A L M ATER IA LS SCIENCE

USING LIGHT TOESTABLISH A NEW
FIELD OF CHIRAL
MATERIALS
Understanding the universal property of chirality
could lead to new materials and technologies
for photonics and other applications

Of the many mysteries still to be
unraveled in the natural sciences,
one of the most compelling is theorigin and power of chirality — theproperty of a molecule or object
that has two mirror-image forms— like our left and right hands.
Chirality is universal in biology,
chemistry and physics. It criticallyaffects the biochemical processes
underpinning life, is a vital aspectof drug discovery, and crops up
in particle physics. Light can havechiral properties that affect how itinteracts with matter. But how can
the power of chirality be harnessed

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and controlled? And what new
discoveries and technologies might
this give rise to? These are some ofthe questions Takashige Omatsu andhis team are asking.
Light beams can be chiral when
they are imparted with so-called
helical wavefronts, that is, polaritythat rotates either left or right.
“We can use ‘optical vortices’ totwist the physical properties ofmetals, semiconductors and organic
materials on the nanoscale to createchiral nanostructures with uniquefeatures,” says Omatsu. “Our goal isto establish chiral photonic materials

The property of
having two mirrorimage forms — likea left and a righthand — is known
as chirality andabundant in nature.

as an original research field and topioneer new technologies such as
chiral plasmonics and metasurfaces
for nanoscale chiral chemical
reactors, chiral-selective imagers andchiral sensors,” he explains.
LIGHT CORKSCREWS
Omatsu’s team focuses on theinteraction between helical light andmaterials, and the physical properties
and potential uses of such modified
materials. The electromagnetic fieldof helical light rotates as the lightmoves through space. When this fieldinteracts with conductive materials

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LEFT-HANDED
MATERIAL

RIGHT-HANDED
MATERIAL© ANDRZEJ WOJCICKI/SCIENCE PHOTO LIBRARY/Getty

A LIGHT TWISTIn optical vortices, light twists likea corkscrew in either a right or left
direction. This vortex appears as a ring oflight on a flat surface moving in a specificdirection. Optical vortex illumination
can be used to twist materials to form
nanostructures that have either a left- orright-handed symmetry, giving themdifferent properties.

R E S E A R C HSpace in thenanoscale“Our research might
one day allow us toanswer the scientificmystery: ‘Why does
handedness exist
in nature?’” says
Takashige Omatsu.

10µm

10µm

5µm

5µm

5µm

5µm

© Reproduced, with permission, from K. Toyoda et al. Nano Letters 12, 3645–3649 © 2012 American Chemical Society, under terms of ACS AuthorChoice license

Orbital angularmomentum

Scanning electron microscopy images oftwisted nanoneedles fabricated by
Omatsu’s team using
optical vortexes.

like metals, nanoscale corkscrew-likevariations in physical properties canbe inscribed on the material’s surface.
The modified surface can then react
differently to left- and right-handedchiral molecules or helical light,
giving rise to a range of interesting
possibilities for chemical sensing,synthesis and imaging.
“We can use helical light to create
nanostructures such as twisted
needles, twisted reliefs and twisted
fibers,” says Omatsu. “We have also
found that the same process canpolymerize fullerene — a well-known
functional organic molecule that isnormally not conductive. This causes
fullerene to form a novel conductive
metallic phase, which could be
used as the basis for fabricating
electronic devices without metals
and semiconductors.”
Omatsu believes ‘nanovortices’
will one day be used for nanoscaleprecision control of light polarization,
electron orbital motion and theaggregation of chiral molecules.
“Our research will lead to materials
for next-generation photonics andelectronics, and new applications
in chemical synthesis, pharmacy,
biology and medicine,” he says.

“It might also allow us one day toanswer the scientific mystery: ‘Why
does handedness exist in nature?’”Omatsu has collaborated withmany Japanese and international
researchers, and is always looking
for students and early career
researchers. “Our research center
brings together physicists, chemists,biologists and even medical doctors,
and we frequently have brainstorming meetings to think up ideas
for new projects,” he says. “Several
international researchers work here.
There is a wonderful diversity ofbackgrounds and expertise.”

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IN TER NATIONA L CEN TER FOR H A DRON A STROPH YSICSREVEALING
HIDDEN MESSAGESFROM THE COSMOS
From a remarkable observatory buried deep inthe south polar ice, Chiba University astrophysicists are
helping to explore the origins of the Universe

Humans have been observing the stars
for tens of thousands of years, first with
our eyes, then with optical telescopes, andmore recently using devices that can detect
light at the extremes of the electromagnetic
spectrum far beyond the visible range. Yet
despite phenomenal progress in astronomy
over the past half century, much of the
Universe remains completely hidden fromview, obscured by other matter, otherradiation sources, and light’s interaction
with the interstellar medium.
Now, scientists are on the verge ofbeing able to peer into some of the mostmysterious corners of the cosmos using
not light but neutrinos — near-massless
subatomic particles that travel close to the
speed of light across the Universe without
being deflected by magnetic fields orabsorbed by matter.
The International Center for Hadron
Astrophysics (ICEHAP) led by Shigeru
Yoshida is part of the global collaboration
responsible for constructing the IceCube
Neutrino Observatory deep in the ice at
the South Pole’s Amundsen–Scott station.
“One of the longest standing puzzles inastrophysics is the origin of high-energy
cosmic rays and neutrinos,” says Yoshida.
“The new windows to our Universe

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opened by neutrino observations,combined with powerful computer
simulations of cosmic plasma, have great
potential to finally resolve this mystery.”THE ICECUBE COLLABORATION
Neutrinos are the most abundantparticles in the Universe after photons(light particles). They originate in someof the most violent and least understoodcosmological phenomena like supernovas,
galactic cores and black holes. After
their birth, they travel in straight lines
from their source with almost no
deflection or absorption, making them
ideal messengers from the heart of thesemysterious astronomical objects. But
these same properties also make themexceedingly difficult to detect.
The IceCube collaboration, involving
300 physicists from 48 institutions in 12
countries, has gone to extreme lengths
to detect these ghost-like, high-energy
particles. The IceCube observatory is a
cubic kilometer of crystal-clear ice, deep
below South Pole Station — the only place
on Earth where such large volumes ofclear, pure and stable ice can be foundalong with the infrastructure needed tosupport scientific research.

AmundsenScott station in
Antarctica.

By suspending thousands of delicate
photodetectors on strings in a networkof vertical holes drilled through the ice,
physicists can capture the rare explosionof energy that occurs when a neutrino
collides with an oxygen or hydrogen
nucleus. Of the trillion, trillion neutrinos
that pass through IceCube every day,the facility records just a few hundred
collisions from high-energy neutrinos — aminute fraction of the neutrino flux but
more than enough to stimulate some very
exciting research.
Another important contribution of
ICEHAP to understanding the high-energy
Universe is its supercomputer-based
massive numerical simulation programfor deep investigation of the physicalmechanisms behind high neutrino
production. “We are proud of having been
key players in the discovery of high-energy
cosmic neutrinos, which astrophysicists
have been dreaming about for more than
30 years,” says Yoshida. “This is a big
step forward in astrophysics. Throughour simulations we are helping to uncover
the hidden messages carried by theseneutrinos and to reveal the physicalmechanism by which high-energy cosmic
rays are accelerated at their source.”

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Image courtesy of Felipe Pedreros, IceCube/NSF

Two towers receive
information from 5,160
light-detecting sensors buried
2,500 meters beneaththe South Pole.

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THE ICECUBE NEUTRINO OBSERVATORY, at
the South Pole’s Amundsen–Scott station. The
International Center for Hadron Astrophysics is partof the global collaboration constructing IceCube.

Strings of opticalsensors reach
depths almost
eight times theheight of theEiffel Tower.

Neutrinos are subatomic
particles that typicallypass freely through matter.
Other particles cannot
penetrate the Earth, so
below the ‘Dark Sector’
near the South Pole,
free from every otherinterference, it is quiet
enough for the neutrinos
to be detected.

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PH Y TOCHEMIC A L PL A N T MOLECU L A R SCIENCE S

UNLOCKING THE POTENTIAL
OF PHYTOCHEMICALSAdvanced genetic and genomic techniques are transforming our understandingof how phytochemicals can improve human health

Since ancient times, people have used
the natural compounds in plants, known
as phytochemicals, for medicinal andnutritional use. Now, scientists at Chiba
University are using advanced genetic
and genomic techniques to verify
how phytochemicals are generated inplants, how they can be manipulated
to optimize certain plant groups, andhow they may help tackle lifestyle- andaging-related diseases.
Plants naturally generate chemicals
for various purposes, including for
attracting pollinators and defending
themselves. These specialized
metabolites allow plants to colonize
specific niches in the food chain, adapt
to new environments and evolve tosurvive potential stressors. Crucially,
phytochemicals also exhibit properties
that can help treat human diseases.
Examples in modern medicine include
morphine, the antimalarial drug
artemisinin and chemotherapy agents
derived from taxanes.
ENLISTING PHYTOCHEMICALSTO FIGHT DISEASE
Kazuki Saito, who leads the
Phytochemical Plant Molecular
Sciences program, says that because
phytochemicals display considerable
natural diversity, they have huge

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potential to fight disease. “Althoughphytochemicals have been used inpharmaceuticals and ancient remedies
for many years, it is only now, withthe advent of next-generation DNA
sequencing, that we can really begin tounderstand how they work and unlock
their full potential,” says Saito.
The program consists of threecollaborative research groups, eachworking on a specific theme.
One group is focusing on the
genomics of medicinal plants and foodcrops with the key aim of revealing the
genomic principles of phytochemical
production. Employing state-of-the-art
technologies, the researchers identify andclarify the roles of unknown genes, aswell as investigate plant metabolism.
In 2016, Saito’s team assembled adraft genome for licorice (Glycyrrhiza
uralensis), which is used worldwide asa natural sweetener and a medicinalcomponent. They identified several
components known to play a positiverole in human health within the plant,
while pinpointing key genes, themanipulation of which could lead tocrop improvements.
The second team is identifying novel
phytochemicals and active products ina wide variety of plants, searching for
drug components to tackle diseases

such as cancer, dementia and diabetes.
As well as isolating and analyzing
promising molecules, the groupconducts animal trials to assess thepharmaceutical potential of molecules.
In particular, they have extensively
investigated Lycopodium alkaloids(LAs), molecules found in the vascularplant Lycopodiaceae, which may
help to treat Alzheimer’s disease andschizophrenia.
The third group is investigating
how plants respond to different
environmental stresses by growing
plants in different artificial environments
and monitoring their responses
to change.
“Our aim is to optimize plants
so that they produce high-quality
phytochemicals that we can harvest for
use in medicines and functional foods,”
explains Saito. “Our insights will enable
us to grow rare plants more successfully
and will also inform agricultural practices
for commercial crops in the future.”
While the group is focusing on
phytochemicals, it also conducts
wide-ranging interdisciplinary studies
and hence welcomes researchers andstudents with backgrounds in chemistry,horticulture, genetics and pharmacy who
are interested in this exciting and rapidly
developing area of research.

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R E S E A R C HDistribution of genes in Medicago
truncatula chromosome.

Distribution of genes in
Glycyrrhiza uralensis
chromosome.

© 2016 K. Mochida et al. The Plant Journal 89, 181–194

CHINESE LIQUORICE GENOME
In 2016, Kazuki Saito sequenced theentire draft genome of Chinese liquorice(Glycyrrhiza uralensis), a plant used in
traditional medicine and as a natural
sweetener. Experimental and clinicalstudies suggest that Chinese liquorice
has a wide range of pharmacologicaland protective properties.
This diagram is a circular representationof the gene distribition in the G. uralensis
chromosome (red) compared withanother legume whose chromosome
had been previously sequenced,
Medicago truncatula (grey), mapped
against their gene densities and genes
involved in the production ofa sweetening compound.

Gene density inM. truncatula (grey) and
G. uralensis (red) chromosomes.

Genes involvedin the productionof the sweetening
compound,glycerryzhin.
Comparing thesegenes in two
species could
help researchers
to identify
those that haveuseful biological
functions.

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C E N T E R F O R I N N O VA T I V E M I C R O WAV E R E M O T E S E N S I N G

THE NEXT WAVE INREMOTE SENSING
Five meters long, with awingspan of 6 meters, JX-2
has a light carbon framethat can carry 25 kilos of
sensor equipment.

The Josaphat Microwave Remote Sensing
Laboratory (JMRSL) is far more than alaboratory. It is an experimental aerospace
workshop where world experts in remotesensing collaborate with mechanical andaerospace engineers to construct state-ofthe-art microsatellites and airborne sensors.
The JMRSL specializes in microwave-radar
technology for detecting ground movements
and earthquake predictors as part of a newgeneration of remote sensing technologies.
“Microwave radiation is particularly usefulfor remote sensing because it penetrates cloud,haze and fog, allowing us to observe the Earth’s
surface from space,” explains Josaphat Tetuko
Sri Sumantyo, the laboratory’s namesake.
The core area of research at the JMRSL
is the development of synthetic apertureradars (SARs) for microwave remote sensing
to monitor land deformation. SAR emits a
microwave signal in the direction of the target
and then detects microwaves scattered fromthe target. By comparing SAR images obtained
before and after a change such as an earthquake
or a landslide, researchers can determine howmuch the land has moved.
The JMRSL has a well-developed researchand-development program with 15 researchers,
25 students and facilities for designing,
manufacturing, calibrating and operating SAR
for both aircraft and microsatellite applications.
ADVANCED AEROSPACE FACILITIES“Our facilities include an anechoic chamber
for calibrating sensors, a satellite–groundcommunication system, and microsatellite
calibration and measurement systems. We
also have a simulator for designing microwave
circuits and antennas, along with a suite of
manufacturing equipment,” says Sri Sumantyo.
“We even have our own 6-meter experimental
unmanned aerial vehicle, the JX-1, which wedeveloped in this laboratory.”

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The JMRSL has already developed SAR
sensors for circularly polarized (CP) microwave
radiation in the L, C and X bands, which havebeen deployed on both large and small aircraft,as well as on the JX-1. The CP-SAR sensor is thefirst of its kind, utilizing interference between
left- and right-handed circularly polarized
light to obtain precise information about the
Earth’s surface in a compact, lightweight andinexpensive sensor.
“With funding from the governments ofJapan, Malaysia, Indonesia and Korea, wehave developed several techniques based on
SAR imaging to monitor infrastructure andareas affected by disasters such as forest fires,
landslides, subsidence and volcanic eruptions,”
says Sri Sumantyo.
Engineers at the JMRSL are developing two
novel microsatellites. One is equipped with radio
occultation and electron density temperatureprobe sensors for measuring the atmosphericsignatures thought to precede earthquakes,
while the other is a CP-SAR satellite withlightweight gold-coated mesh antenna. Thesesatellites are poised to take the lab’s researchbeyond the stratosphere.
“Our microsatellite program is very exciting
for future SAR sensor applications and planetary
exploration,” says Sri Sumantyo. “We eventually
aim to have five microsatellites in orbit, which
will provide real-time monitoring for global
disaster mitigation and research. Right now,
we are preparing to build our first engineeringmodel, with the flight model to come soon.”
The JMRSL has strong collaborations withJapanese and overseas research institutions andindustry — it has more than 50 agreementswith research and industry partners throughout
the world. The group also encourages
short- and long-stay programs under various
government programs, through which morethan 500 students and researchers from manydifferent countries have worked at the lab.

© Josaphat Microwave Remote Sensing Laboratory, Chiba University

Microsatellites and remote imaging technology
are revolutionizing the way we predict earthquakes
and monitor disaster zones

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JX-2 is the second aircraft built by
Sri Sumantyo’s team, and one ofmany they plan to build, including
smaller aerial vehicles for short- andmedium-range coverage.

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IN PLANE VIEW
Josaphat Tetuko Sri Sumantyo’s teamat Chiba University built the unmanned
aerial vehicle JX-2, which is equipped withmicrowave sensors that can penetrate
clouds to scan the Earth.

Circularly polarized synthetic
aperture radars(CP-SARs) affixed to aircraftor microsatellites can obtain
precise information about the
Earth’s surface.

CP-SAR sensors measure
the microwaves scatteredfrom a target to detectchanges in land, ice, ocean
and forest cover.

Microwave radiation
is a useful tool formonitoring disasterzones or assessing
a site, such as
following a landslide orearthquake.

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M U LT I MODA L M E DIC A L E NGI N E E R I NG

TOWARD IMAGE-BASEDDISEASE DIAGNOSTICS
Novel, high-precision imaging techniques are being used to provide
non-invasive disease diagnosis and guide future treatments
First, optical images arecollected of the diseased tissue.

Non-invasive, precise diagnosis of
diseases using advanced medical
imaging technologies could one
day replace traditional techniques
based on biopsy and dissection.
With this prospect in mind,
researchers at the Multimodal
Medical Engineering program are
combining medical and engineeringexpertise to create novel, noninvasive imaging-based methods
for diagnosing and treating disease.
The program uses
various scanning techniques,or ‘modalities’, including
computerized tomography,
magnetic resonance imaging (MRI)and ultrasound, to analyze cellularand organ variations caused bydifferent diseases.
The program’s goal is to develop
highly precise, non-invasive imaging
methods, while boosting existing
imaging techniques to improve
resolution and enable more-detailed
tissue analysis, says program leader
Hideaki Haneishi.
“Many current diseasediagnostics, particularly for cancer,
involve highly invasive, unpleasant
procedures to clarify the type andstage of the disease,” explains
Haneishi. “We are investigating,for example, the developmentof a system to diagnose
breast cancer using very-highfrequency ultrasound.”Rather than physically samplingand dissecting lymph nodes frompotentially cancerous tissue, his

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LAYERING THE BRAIN
Multimodal imaging techniques can offer a moredetailed insight into health and disease. In thisexample, researchers at Chiba University havecombined different kinds of imaging taken of a cancer
patient’s brain to assess tumor pathology: optical,
pathological and magnetic resonance images.

team has shown that it is possible
to analyse cell characteristics oflymph nodes using ultrasound. Theirtechnique highlights metastasis
positive and negative cells in
lymph nodes, enabling rapid,
painless diagnosis.
Haneishi and his team are also
devising ways to combine datafrom two or more modalities. For
example, in 2016 they developed
an image registration method thattransforms two data sets into one
coordinated system using MRI andpathological images of brain tumors.
“If we can establish thetechnology for registering two
kinds of images, then MRI featuresthat are strongly related to thepathological features of tumors canbe highlighted. This may eventually
allow us to diagnose using only
MRI,” says Haneishi. “Determining
the relationships between different
data sets helps us build up detailed
pictures of what is going on inside
the body, not only for diagnosis but
also to improve our understandingof disease development,” he adds
NOVEL OPTICAL PROBES
Alongside conventional imaging
techniques, the researchers arealso exploring novel optical probes.
One example involves a method
for monitoring microcirculation —the flow of red blood cells — inthe body. The probe comprises
multicolored light-emitting diodes

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Pathological images
are then sliced,
digitized andreconstructed like a
jigsaw puzzle.

(LEDs). As the LED light is scatteredthrough the tissue, it is partly absorbed
by molecules in the red blood cells,
generating a clear, detailed picture of thecells and their microcirculatory network.
Building on previous work, the teamhopes to use this probe to estimatefeatures such as the oxygen saturationof each blood vessel in areas aroundsuspected tumors in real time. This
could aid diagnosis and further our
understanding of vascular behavior in
and around tumors. “Ultimately, we
would like to build on these imaging

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techniques and use machine learningand artificial intelligence technologies torelate measured signals and diagnoses, todevelop a comprehensive understandingof different diseases,” says Haneishi.
The Multimodal Medical Engineering
program has access to highly specialized
equipment and technologies that canhelp realize researchers’ ideas.
“We welcome engineers andmedical researchers who wish towork at the cutting-edge of researchand development with direct clinicalapplications,” says Haneishi.
Finally, the optical andpathological images aresuperimposed onto threedimensional magnetic
resonance imaging slices to
get an in-depth view of thecancerous tissue.

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C H I B A S T U DI E S O N G L O B A L FA I R S O C I E T Y

FORGING A FAIRER WORLDA multidisciplinary team of researchers looks at how tocreate a fair society — on a global scaleWith globalization comes the need toensure that people from all cultures,countries and backgrounds aretreated fairly and equally. The drive tocreate a just global society requires
solid foundations in all countries,
backed by informed government
policies and strong support networks
at local, regional and national levels.
Much previous research into justiceand social change has been dominatedby studies of Western societies, but
the rapid changes experienced by
Asian countries in recent decades
have spawned a growing field of
research focused on building fairsocieties in Asia.
Researchers in law, politics,
economics and social sciences
have recently established the Chiba
Studies on Global Fair Society
project, with the aim of creating
an interdisciplinary research baseto inform future local, national andinternational policies.
Lead researcher on the project,
Jiro Mizushima, says the key concept
is fairness. “We define fairness as thebasic element of justice,” he explains.
“In fact, we argue that it exceeds
justice in most cases. At the sametime, we embrace values such as
equality and liberty.”
Mizushima, whose researchinterests lie in welfare state reformin Europe, says the project aims to
go beyond the traditional discussionof equality — it seeks to construct
new principles that value diversity
among people in a global society.
HOW DO WE ACHIEVE A
FAIR SOCIETY?
The project consists of fourinterrelated research groups and afurther six teams working to publicize
the findings to a wide audience.
Their focus is on challenging andovercoming unfair practices on all
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scales, investigating issues such as
gender inequality, widening income
gaps, migration, and the collapse ofregional and marginal communities,
both in Japan and around the world.
The key aims of the project are
to investigate the development,
transformation and limitations ofexisting welfare state models andto provide empirical evidence for
how a fair society can be achievedin the 21st century. Mizushima has
spent considerable time researchingaspects of the welfare state in the
Netherlands, including how it has
responded to social challenges suchas global economic fluctuations andan aging population.
“Fairness has been the core oflegal and political philosophy sinceancient times, and so another of
our teams is examining equality
and fairness from a historicalperspective, comparing political,
economic and legal standpoints overtime,” he says. “Another group will
analyze the meaning of fairness inthe 21st century, providing us with
fundamental guidelines to underpin
our program.”
The team plans to form networksof academics across the globe. To
this end, they have hosted two highly
successful international symposiums
and another one is planned for later
this year. “Many of our members are
involved in local and national policymaking committees, and they are
key to informing policy makers of ourwork,” says Mizushima.
The project welcomes thoseinterested in all aspects of social
science, from law and politics tosociology and economics. Students
and researchers alike will receive
training from scholars in their own
field and other program members,
allowing them to broaden theirresearch interests.

The Chiba Studies on Global
Fair Society project goes beyond
traditional discussions of equality
to construct new principles thatvalue diversity among people in a
global society.

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ONE WORLD, MANY VOICES

Despite widespread differences inlanguage, customs and cultures,the world is becoming increasinglyinterconnected. Creating a society
where people of all cultures,countries and backgrounds aretreated with fairness and equality
requires a global effort.
“We define fairness as thebasic element of justice,” says
Jiro Mizushima. “We embracevalues such as equality and liberty.”

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Solar cell technologies
today are not efficientenough to produce
energy on a large scale.

HIGH-EFFICIENCY ENERGY CON V ER SIONTOWARD A ZEROEMISSION SOCIETY
The future of clean energy production lies in perfecting
the nanoscale details of fuel cell components to create aninnovative carbon-neutral energy system

The race is on to find ways to replace
our reliance on fossil fuels with clean,sustainable methods of generating power.
Current solar and hydrogen technologies
are not yet efficient enough to produce
energy on a large scale. With this in mind,
researchers from the High-Efficiency Energy
Conversion program aim to improve current
solar and hydrogen fuel cells, while finding
ways to reduce the pollutants already inthe environment.
“We hope to develop efficient energy
conversion systems that don’t emit carbon
dioxide and pollutants,” says Nagahiro Hoshi,
lead researcher on the program. “We will
create a system that generates power
fueled by sunlight and water. To do this,
we must perfect the structures of thenanomaterials used to make solar andhydrogen fuel cells to optimize their ability toharness energy.”
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Hoshi’s team works with various
nanostructures, including nanoparticles,
single-crystal surfaces and organic
nanoassemblies, to build devices thatcan capture as much energy as possible
without wastage.
ENHANCING ENERGY CONVERSION
The surface structures of catalysts used insolar cells and hydrogen fuel cells can have aremarkable impact on conversion efficiency.
For example, the orientation of atoms on asolar cell’s surface significantly affects the
distribution of light across the cell.
One way of enhancing a solar cell is tocoat its surface with a dye. The dye’s atomic
make-up contributes to the cell’s ability togenerate electric current when exposed
to light, providing it is adsorbed onto an
appropriate surface. The researchers recently
explored the effects of using a zinc porphyrin(ZnP) dye on single-crystal titanium dioxide(TiO2) substrate surfaces. They trialed threedifferent TiO2 substrates and found that theirsurface structures significantly altered theability of the ZnP dye to generate an electric
current efficiently. In fact, one of the ZnP
TiO2 substrates had an incident photon-tocurrent conversion efficiency 13 times higher
than one of the others.
Hoshi attributes the high conversion
efficiency on this substrate to the bent
configuration of the adsorbed porphyrin ring,which results in a shorter distance between
the ring and surface. Such attention to detailin terms of nanoscale surface structures will
generate the breakthroughs needed to create
highly efficient, scalable and cost-effective
solar power.
At present, hydrogen is mainly
manufactured by using heat and pressure
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Altering
the surface
structure ofcatalysts usedin solar cells
can improvetheir efficiency
exponentially.

120,000 terawatts(TW) of energy
flow from the Sun
constantly.

SOLAR POWER
POTENTIAL© gerenme/E+/Getty

Global solar electricity potential exceeds current andprojected capacity by several orders of magnitude.

this manufacturing process also creates large
amounts of carbon dioxide, scientists are
exploring ways to generate hydrogen from waterinstead. When burned, hydrogen releases only
water and steam, and it has the potential to fuelall kinds of systems. Hoshi’s team has developed
a hydrogen-based method that could transform
excess carbon dioxide into usable fuel.
“We are researching photocatalysts capableof decomposing pollutants such as carbon
oxides, ammonia and waste oil,” says Hoshi.
“We have had recent success in investigating
the photocatalytic conversion of carbon dioxide
into methane — the reaction pressure needed
to reduce the carbon dioxide was created usinghydrogen gas.”
To help realize this vision of a zeroemission society, Hoshi and his team welcome
collaborations with researchers and privatecompanies interested in this burgeoning fieldof nanotechnology.

21.6 TW global
electricity demandin 201225.8 TW projecteddemand in 2020

36.5 TW projecteddemand in 2040

0.09 TW global
solar capacity
in 20120.35 TW projected
capacity in 2020

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C A NCER EPIGENOME CEN TERA DIFFERENT APPROACH
TO FIGHTING CANCER

Methyl tags
attached to
DNA can turngenes on or off.

UNRAVELING MOLECULAR MECHANISMS
Kaneda points to ongoing investigations ofgastric cancer as an example of this strategy
in action. Patients with this cancer exhibit
different levels of DNA methylation in theirtumor cells, depending on the pathogen
responsible for the disease. The cancer-

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causing bacterium Helicobacter pylori is one
source of irregular methylation, infection
with Epstein Barr virus is another. Both seemto have profound epigenetic impacts on
stomach cells, leading to the silencing of manytumor suppressors.
Kaneda and his colleagues are using clinicalsamples and cell experiments to unravel themolecular mechanisms that induce hyperactive
methylation patterns following infection withthese pathogenic agents. They ultimately hopeto stop the process in its tracks.
Similar projects are ongoing to combat
colorectal cancers — which Chiba researchers
have shown can be categorized into three
types, depending on methylation levels —as well as blood cancers and other typesof tumor.
With an eye to developing novel
therapeutics, chemists at the Cancer
Epigenome Center are working on new
methods to efficiently synthesize moleculesthat can act on epigenetic aberrations. One
such group of molecules is the pyrroleimidazole polyamides. These molecules
can bind to DNA at specific sites in the
genome, and when coupled to an epigenetic
inhibitor they can prevent methylation-based
gene silencing. Kaneda hopes to deploy themolecules to edit the epigenome at targeted
regions to regulate tumor formation.
The Cancer Epigenome Center includes
researchers from a wide range of backgrounds
and specialties. This multidisciplinary teamapproach, says Kaneda, is essential forturning the center’s discoveries into clinicallymeaningful treatments and diagnostic tools.
“We will help determine the mechanisms ofcancers and develop new cancer drugs throughcollaborating with experts in medicine, physics
and pharmacy,” he says.

© National Institute Of General Medical Sciences/National Institutes Of
Health/Science Photo Library/Spl Creative/Getty

Cancer is thought of as a genetic disease, with
mutations to a cell’s DNA causing a normal
cell to give birth to a malignant tumor. Yet
epigenetic alterations, which leave the DNA
sequence intact, can be just as important ina cell’s transformation to cancer. Even thoughepigenetic regulation through mechanisms
such as methyl tags and histone modifications
does not alter the DNA sequence, it canchemically modify the genome to signal
which genes should be turned on and off.
When tumor-suppressor genes are silenced
or oncogenes are activated in this way, manydifferent forms of cancer can result.
Fortunately for medicine, epigenetic
alterations are not permanent. They can beundone to prevent or reverse cancer, leaving
a cell with its entire complement of normal
DNA intact.
This is exactly what researchers at theCancer Epigenome Center are striving to do.
Led by Atsushi Kaneda, the center is seeking tounderstand the various epigenetic drivers that
contribute to different types of cancer and thendevelop new drugs that overturn these effects.
“We will explain key epigenomic aberrations
and their molecular causes,” says Kaneda.
“And then, taking advantage of small
molecules that bind to DNA in a sequencespecific manner, we will develop drugs thatcan rewrite the accumulated epigenomic
aberrations or prevent them accumulating intargeted genomic regions.”© lumpynoodles/DigitalVision Vectors/Getty

A new center aims to combat cancer by rewriting the epigenetic
modifications harbored by tumor cells

DNA winds aroundspool-like proteins
known as histones.

Chromatin refers
to DNA that is
wrapped aroundhistone proteins likebeads on a string.

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The human genome
contains anestimated 3 billion
base pairs in linked
strands that twist toform a double-helix
structure.

Histone tails
chemically modify
histone complexes
to signal whether
a region of DNA
should be ignored or
activated. The more
tightly wrapped thehistone complex, theless accessible it isfor translation.

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THE EPIGENOME
The combination ofchemical tweaks in acell that affect gene
expression without
directly altering the
DNA sequence is known
as the epigenome.
Differences in the waythat DNA expression isregulated can explain thediversity of cell types inthe body, but can also be
a powerful mechanismof disease.

Bacteria and viruses
can disrupt thenormal process of
DNA methylation,
which can cause
cancer.

A nucleosome is
one structural unit consistingof some DNA coiled arounda histone.

The chromosome is atightly wrapped structure
containing part or all of thegenetic code of an individual.
Most human cells have a
total of 46 chromosomes ofscrunched DNA.

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IN TEGR ATED R ESE A RCH CEN TER ON R EGENER ATI V E SYSTEMS A ND DISE A SESSTEEPED IN STEM CELLS
New cell therapies, drugs and disease insights should flowfrom a coordinated approach to stem cell research

Stem cells have the remarkablecapacity to both self-renew andgive rise to many types of more
specialized cells in the body, which
explains their great therapeuticpotential in regenerative medicine.
But that is not the only reason stem
cells have become such a hotbedof scientific inquiry — these cellulartransformers are also an invaluable
research tool for probing thedisease mechanisms that underpin
cancer, aging and a host of other
health problems.
At the Integrated ResearchCenter on Regenerative Systems andDiseases, Chiba University scientists
are advancing both these avenues ofstem cell research. Some researchers
are focused on developing new kindsof therapies based on stem cells,
while others are gaining important
insights into disease biology.
However, they all share the common
goal of improving the lives of patientsusing stem cells as their tool.
The center, which opened in 2016,is divided into three main researchgroups. The first is dedicated tousing stem cells found in the bloodand brain to better understanddisease and normal development; thesecond focuses on reprogramming
tissue biopsies taken from patientsto make disease-specific stem cells
for drug screening; and the third isdeveloping stem cell therapies fortreating diabetes, heart disease andother disorders.
Center director, Atsushi Iwama,
says their work covers a wide
spectrum, from basic to clinical

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Megakaryocytes
are rare bonemarrow cells
formed from stem
cells that can giverise to every typeof blood cell inthe body.

Cell nucleus

STEMMING BLOOD
Koji Eto at Chiba
University and Kyoto
University has developed
a protocol to turn stem
cells (left) into precursorsof platelets (right), withthe long-term goal of
producing enough bloodfor patients in need oftransfusions.

research. Yet despite different
researchers adopting different
approaches, they all work in acollaborative manner, holding regulargroup meetings and retreats where
new data are discussed and newalliances forged.

COLLABORATIVE PARTNERSHIPSAROUND THE WORLDThe Integrated Research Center isalso looking further afield to create across-disciplinary research networkthat spans the globe. It has alreadyformed partnerships with otherC H I B A

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Megakaryocytes can be induced into proplatelets
and cytoplasmic fragmentation, precursors ofplatelets, which are disc-shaped cells found in large
volumes in the blood.

© Koji Eto

The first human trial using platelets derived fromstem cells, led by Eto, could be extended to patientsin need of blood transfusions at Chiba University.

leading stem cell research groups inJapan, Singapore and the United States,
and it hopes to build more international
connections in the future.
One of those partnerships is with
Kyoto University’s Center for iPS Cell
Research and Application, where
Koji Eto has worked for years developing
a protocol for making platelets from
reprogrammed stem cells. Last year,
Chiba University recruited Eto to join
its new center. And while Eto will
maintain a lab in Kyoto, where heplans to run the first human trial ofplatelets derived from stem cells, hehopes to expand the study to include
patients needing transfusions at Chiba
University Hospital.
Other notable members of theIntegrated Research Center on
Regenerative Systems and Diseases
include Koutaro Yokote, a leading expert
on a form of progeria known as Werner
syndrome, and Chiaki Nakaseko, a world
leader on a rare plasma cell disordercalled POEMS syndrome. Yokote ismaking stem cells from patients with
Werner syndrome to better understandthe disease and find new drugs, while
Nakaseko is focused on developing new
kinds of transplantation therapies fromstem cells derived from bone marrow.
These and many other worldrenowned investigators make the new
Chiba center an ideal place to work andtrain the next generation of scientists.
“We hope to recruit many young peopleinterested in stem cell research andclinical translation,” Iwama says.

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MEDIC A L M YCOLOGY R E SE A RCH CEN TERMANIPULATINGMICROBES FORHUMAN HEALTH
Detailed investigations of host–microbe interactions
could yield new therapies against infectious agentsand autoimmune diseases

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scholars, together with others from around theworld, convene each November at the Medical
Mycology Research Center for the annual Global
Network Forum on Infection and Immunity.
EXPLORING HOST–MICROBE INTERACTIONS
The team that Yoneyama has put together
is roughly divided into four groups, eachstudying molecular interactions in different
host–microbial systems. One, led by Shinobu
Saijo and Yuumi Nakamura-Matsuoka, isfocused on fungal infections in the skin of miceand humans; another, led by Koichi Hirose
and Tomohiro Tamachi, is investigating the
microbes — both good and bad — that residein the respiratory tract. A third group, which
includes Yoshiyuki Goto, is concentrating on
the gut microbiome and how opportunistic
intestinal infections gain a foothold; while thefourth, led by Akiko Takaya, is working on morebasic mechanisms of immunological memory in
response to microbial invaders.
“Results obtained from our projects will help
efforts to create innovative new therapeutics
against infectious diseases and will eventuallylead to improvements in human health,” says
Yoneyama, whose own research focuses on themechanisms of innate antiviral immunity.
To assist all these research projects,
investigators from each group have access to
the Japanese government’s network of corefacilities — a resource known as the Joint
Usage/Research Center, which is staffed by
specialized researchers and technicians who
can run state-of-the-art experiments, including
with fungi and other microbes. A bioinformatics
unit at Chiba led by Hiroki Takahashi helps withcomputational analyses.

© David Spears FRPS FRMS/Corbis Documentary/Getty

The human body is made up of a staggering
30 trillion cells or so. But just as numerous,
if not more so, are the trillions of microbial
co-inhabitants that teem in and on us. These
commensal bacteria and fungi are essential to
our well-being, and a distortion in the microbialbalance can trigger a wide range of disorders,from acne to obesity.
Only recently, however, have scientists cometo appreciate just how critical this collection of
microbiota is for determining human health anddisease. They are also becoming excited about
the prospect of how manipulating this microbial
ecosystem could form the basis for the next
generation of life-saving therapeutics.
Led by Mitsutoshi Yoneyama, researchers at
the Medical Mycology Research Center havelaunched a comprehensive research effort todissect the intricacies of host–microbe interactionsin the skin, lung, intestines and spleen.
“Dysregulation of host–microbe interactions
can give rise to a wide variety of humandisorders, including opportunistic infections,allergies and autoimmune disease,” explains
Yoneyama. “It is hence crucial to understandhow hosts and commensal microbes
communicate as a superorganism.”
Creating a superorganism is an apt metaphor
for what Yoneyama is trying to achieve because,through the melding of minds from across Chiba
and around the world, the center can make a
far greater impact than any individual scientist
working independently. At Chiba University,
the investigators come from the Graduate
School of Medicine and the Graduate Schoolof Pharmaceutical Sciences, while external
collaborators are based in the United States,
Germany and elsewhere in Japan. TheseC H I B A

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E. coli bacteria

Tissue membrane

FRIENDLY BACTERIA
Rod-shaped Escherichia coli
bacteria line the intestinesof humans and otherwarm-blooded animals.
These bacteria are mostly
harmless and play animportant role in digestion,
but some pathogenic
strains can cause disease.

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N E X T- G E N E R A T I O N T H R E E - D I M E N S I O N A L D I S P L A Y A N D M E A S U R E M E N T

FUTURE IMAGES —MORE THAN MEETS THE EYE
Advances in three-dimensional image display and measurement
techniques have applications in multiple fields, from medicine tocommunication and entertainment

LIGHT SHOW
Holograms are threedimensional (3D) images
created using coherent lightsources such as lasers.

The Chiba system
can handle detailed
images composed of amillion points at speedsthat could bring us
closer to the real-time
production of 3D
holographic movies.

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CH I B A U N I V E R S I T Y

Researchers at Chiba
University have produced
holograms using a techniquethat first calculates the display
with high-speed computers
and algorithms. The 3D
images are then observed byilluminating laser light on aliquid-crystal flat-panel display.

© Timo Buchner/Alamy Stock Photo

Technologies based on threedimensional (3D) image displays andholography may conjure up visionsof science fiction, but the Nextgeneration Three-dimensional Display
and Measurement program aims to
make these advanced tools part ofeveryday life.
Holograms create true threedimensional images, which allow
the viewer to see an object fromall angles. They are created using
coherent light sources such as lasers,
which can store the complex lightinterference patterns required toaccurately recreate an entire 3D
object in full color. However, themain drawback of holography is theimmense computational burden of
producing high-quality holograms, notto mention creating moving 3D video
images in real time.
Leader of the 3D program,
Tomoyoshi Shimobaba says his teamis developing ultrafast algorithms anddedicated computers for holography
to create the world’s first real-time
holographic 3D display system.
“These dedicated computers will
have a computational speed threeor four orders of magnitude higher
than the household computers oftoday,” adds Tomoyoshi Ito, advisor on
the project. “Based on this dedicatedtechnology, we will investigate
holographic projection, digitalholographic microscopy and ultrarapid
holographic imaging techniques.”
Among the team’s recent
successes is a small, inexpensive,
zoomable holographic projection
system, suitable for use inclassrooms, medical applications andentertainment products. Shimobaba’s
team refined mathematical image
manipulation techniques to ensure
a high-resolution, non-grainy
holographic image even whenzooming in and out. The researchers
are further developing algorithms
that can reduce ‘speckle noise’in reconstructed images to avoid
degradation in image quality.

ONE IMAGE, MULTIPLE VIEWS
Another aim is to reconstruct large 3D
images with a large viewing angle —something that is difficult to realize
using current technologies.
“We are also developing
accurate holographic measurement
systems, which will be invaluable inmedical science because they allow
researchers to image and measuresamples in 3D alongside visualizing
moving phenomena in real time,”
explains Shimobaba.
In another exciting field of research,
the team is exploring a form of 3Dimage creation called volumetricdisplays — the difference being that,while holograms can only be seenclearly by a few people at a time,
volumetric displays can be viewed
by multiple people from different
viewpoints. And, in an even morechallenging concept, they are trying
to create multi-viewpoint images
with plural information appearing inspecific directions. In other words,
one person standing at one place will
see one piece of information, while
another standing somewhere else willsee completely different information.
“Our volumetric display
simultaneously provides several
observers with different information,”
explains project researcher
Ryuji Hirayama. “This very exciting
feature is quite new, and we areconsidering new applications for using
it, such as developing multi-language
signage for the Tokyo Olympics in
2020,” he says. Such 3D displays
may benefit from advanced aerial
projection techniques, also underdevelopment by Shimobaba’s team.
“Networking is the key to our
success,” says Shimobaba. “Manystudents who have graduated fromour laboratory move on to conduct
research in academia or in privatecompanies, and we continue to workwith them. In this way, we expand
our project and build fruitful working
relationships across academia
and industry.”R E S E A R C H© 2015 Optical Society of America

C H I B A

Computer-generated holograms of a chessboard (top) composed of 44,647 points and amerry-go-round (bottom) made of 95,949 points
created by researchers at Chiba University.

“OUR
VOLUMETRICDISPLAY
SIMULTANEOUSLYPROVIDES
SEVERALOBSERVERS
WITH
DIFFERENTINFORMATION.”

CH I B A U N I V E R S I T Y

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R E S E A R C H A N D D E V E L O P M E N T N E T W O R K O F I N N OVA T I V E M E D I C I N E
FOR IMM U N E R EL ATED R A R E A ND IN TR ACTA BLE DISE A SESINNOVATIVE APPROACH
OFFERS HOPE FORINTRACTABLE PROBLEMSThe ReDenim network is developing therapies
to treat rare and intractable diseases

Scientists at Chiba University have along track record of excellence in clinicalresearch, particularly for investigations inpatients with immune-related diseases. And
Chiba University researchers have made anumber of important breakthroughs in basic
immunology and disease biology. However,connecting these two areas, a field known
as translational research, has often beenless successful.
That is a problem that Shinichiro
Motohashi wants to fix. Motohashi leads
Chiba’s Research and Development Networkof Innovative Medicine for Immune Related
Rare and Intractable Diseases — ReDenim.
The network is aiming to provide the clinicalsupport and resources needed to takediscoveries from the lab to the clinic.
In particular, ReDenim has singled
out two disease areas for which there
are currently no good treatment
options — deadly forms of cancer, such ashead and neck tumors; and rare diseases
that each afflict fewer than 50,000 people
in Japan, but collectively affect about 10 per
cent of the population.
TWO-PRONGED APPROACH
Motohashi and Daiju Sakurai belong to thetumor immunity team, which intends tocapitalize on Chiba University’s expertisein developing cell-based immunotherapies.
Their approach uses tumor-destroying
natural killer T-cells to search for combination
therapies that can further modulate thetumor immune microenvironment in afavorable way. They also intend to identify

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CH I B A U N I V E R S I T Y

Natural killer T-cells area class of white blood
cells that can quickly
recognize and mountan immune response
against tumor cells.

biomarkers that can predict how individual
patients will respond to these treatments.
Led by Sonoko Misawa, the rare-diseaseteam, including Masayuki Kuroda, Akira
Suto and Kiyoshi Hirahara, is using immunemodulating drugs and gene therapies toaddress neurological syndromes, enzyme
deficiencies, inflammatory conditions andrecalcitrant fungal infections.
Kuroda is also working with the cancer
team to develop a transgenic fat cell
technology that has therapeutic applications

for both tumors and the rare metabolism
disorders he is studying.
Importantly, both teams will shareresearch experiences, technology platforms
and manufacturing facilities. “Sharing theknow-how to treat each disease within the
network will accelerate drug development,”
says Motohashi. And the two teams will
also have access to support units at theuniversity’s Core Clinical Research Hospital, adesignation granted to Chiba University underJapan’s Medical Care Act in recognition of

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Cancer cell

© Eye of science/science photo libraryT-cells use membrane
protrusions to explore for
identifiers on the surface ofcancer cells. They kill using
lethal injection.

its ability to apply basic science toward
therapeutic applications. This support
includes consultation services on issues
such as intellectual property, project
management, clinical trial design andother steps needed to fulfill the promise oftranslational medicine.
“Our ultimate goal is to form atherapeutic cluster that can be applied
to a wide variety of rare and intractablediseases,” Motohashi says. He foresees
the infrastructure created through

ReDenim being used to develop new
therapies for common diseases, suchas diabetes or lung cancer. Judging by
the progress they have made so far, theresearchers are well on their way tofulfilling their dream, and their potential
is widely recognized. ReDenim has
already forged collaborations with someof the world’s leading experts in cancer
immunotherapy and rare diseases, and is
working with Japanese drug companies topartner on additional research projects.
CH I B A U N I V E R S I T Y

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S O F T M O L E C U L A R A C T I VA T I O N F O R I N T E L L I G E N T M A T E R I A L S

CATALYZING THE FUTURE
OF SMART MATERIALS
Catalysts developed from soft iodine, graphene and metal complexes could
transform smart material technologies

The very idea of materials that change theirshape or function as required sparks theimagination. Smart materials are impressive
artificial molecules, often inspired by naturally
occurring chemicals, which have the potential
to revolutionize design. They undergo changes
that are reversible and repeatable, meaning
they can function as molecular switches, valvesand sensors. Other smart materials include
shape-memory alloys that return to their
original shape after bending, metal-bearing
polymers that can switch from insulator to
conductor and drug-delivery systems thatslowly release pharmaceuticals where andwhen they are needed.
Researchers at the Soft Molecular Activation
for Intelligent Materials program are leading
investigations into catalysts made from soft
molecules that could one day transform smart
material design.
Lead researcher Takayoshi Arai says the
program is focused on developing powerful
catalysts to create novel smart materials using
three catalyst types. “Firstly, soft halogen
catalysts, predominantly using iodine, can beused to develop highly targeted medications,”
he explains. “A second type is ‘soft ∏-electron’
using carbon nanotubes and graphene, which
would provide a unique reaction sphere forcatalysis. The third type, ‘soft metal’ catalysts
allow us to introduce soft elements such asgold and copper into target molecules.”NEW CATALYST DESIGN
Arai says one of the main goals of the programis to create new asymmetric catalysts, which
are used to generate large numbers of very
specific molecules. Most biological molecules
are chiral, meaning they exist in one of two
mirror-image forms called enantiomers. Many

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CH I B A U N I V E R S I T Y

drugs and smart materials use just one specificenantiomer, and so catalysts are needed todirect the chemical reactions toward forming
the correct enantiomer.
For example, iodine has been used to help
synthesize specific enantiomers of cyclic andring-shaped molecules. “We are lucky that
Chiba prefecture in Japan is one of the world’s
leading producers of iodine,” says Arai. “In fact,
the Chiba Iodine Resource Innovation Center(CIRIC) will open at Chiba University next year.
For this reason, a key goal of our program is toperfect iodine-based soft molecular activation.”
Recent success for Arai’s team includes thedevelopment of an aminoiminophenoxy-copper
carboxylate catalyst that can trigger high yieldsof O-cyclized molecules. These can, in turn, be
used to generate a particular chiral compoundthat is invaluable for use in antimicrobial andantiosteoporotic compounds.
“A crucial part of our research is designing
catalysts that can be reused multiple times,
thereby creating cost-effective, sustainable
methods for generating useful compounds,”
says Arai. His team recently designed arecyclable catalyst made from a zinc-polymeric
ligand complex. The polymeric ligand allows thecatalyst to be separated from the final productby a simple filtration process, meaning it canbe reused — indeed, poly-Zn remained a stable
and active catalyst for creating iodine-based
ring-shaped molecules more than five times.
“By introducing soft elements to target
molecules, our research will facilitate thedevelopment of smart materials with smoothand rapid responses,” says Arai. “We welcome
anyone interested in research at the forefrontof iodine-related soft molecular activation
chemistry to come and work in this diverse andchallenging field at Chiba.”

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Chiba
prefecture 21%

Other 7%

America5%
Rest ofJapan 7%

Global iodine production

Japan is the second-largest producerof iodine in the world, after Chile,accounting for close to 30% of global
production. About 75% of thisproduction takes place in Chiba
prefecture, a hook-like peninsula
on Japan’s eastern coast.
Total production:
33,720 tons/year (2013)© A. & F. Michler/Photolibrary/Getty

Chile 60%

Despite its metallic appearance, iodine is a halogen.

CH I B A U N I V E R S I T Y

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CEN TER OF EXCELLENCE FOR EN D OF LIFE C A R E

PUTTING THE CARE BACKINTO END-OF-LIFE CARE
A new research program recognizes that care for the dying
is an important issue for both public and professionals alikein a rapidly aging society like Japan

Japan is teetering on the precipice of ademographic crisis. Already, people over theage of 65 make up more than one quarter of thecountry’s population. And the fraction of elderly
people is only expected to rise in the years
ahead — it is predicted that in 2060 two out of
every five people in Japan will be senior citizens,
putting huge logistical and financial strains on
the country’s long-term care systems.
The Center of Excellence for End of Life
Care is trying to ease the impact of this skewed
demographic by fostering cooperation between
the public and the professionals who assist
the elderly. The goal, says Center Director
Mariko Masujima, is to develop a coordinatedresearch strategy that ensures all older
Japanese people can live out their final years in
a comfortable and dignified manner with theirwishes and aims fulfilled.
“We have to encourage people in oursociety to talk more openly about their own
end-of-life care,” she says. Only then will thosefacing imminent or distant death have thebest quality of life in the time they have left —regardless of diagnosis, health condition or age.

The new center is housed within the Chiba
Graduate School of Nursing, the oldest school of
its kind in the country. It includes members froma wide range of interdisciplinary backgrounds,
such as ethicists, engineers, health economists
and doctors. These scientists are working
together in four large research groups.
PREPARING FOR LATER LIFE
The first group is focusing on helping the elderly
prepare for what lies ahead. In one project,they have developed a web-based education
tool, which uses a range of animated scenarios
to make users think about common end-oflife problems, such as a health emergency or
the loss of cognitive functions. A prototype ofthe tool received favorable reviews in a small
feasibility study and the team is now adding
new features and functionality to make it moreuser-friendly.
A second group at the new Center of
Excellence is developing a technologicalsurveillance system that deploys remote sensors
to detect physical activity among older residents
in long-term care facilities.

JAPAN’S RAPIDLY AGING SOCIETY“By tracking changes of vital signs andphysical activity in the elderly, the sensors serve
as a tool both for research and for end-oflife care,” explains Masujima. “They can help
nurses and care workers pick up on discomfort
that frail, older residents might not be able toexpress themselves.” The system will soon be
deployed for pilot testing.
The third research group is focusing on
global outreach and has already establishedlinks with researchers in Thailand, Taiwan,
South Korea, Northern Ireland and elsewherein Japan, while the fourth group is developing
educational materials — for both the public andfor other health-care professionals.
“Students need a chance to think more
about end-of-life issues,” Masujima says.
“Unfortunately, our health-care education
focuses almost entirely on treating the living,
but we also need to care for the dying.” The
new center hopes to make that a priority in theface of such a rapidly aging society.

In 2006, Japan earned the‘superaging’ brand, with morethan one-fifth of its population
above 65.

Percentage
of population
above 65

Eldery individuals
accounted for 8%of the world’s total
population in 2015.

By 2050,
projections
estimate thatJapan’s elderly
population willballoon to 40%,
as its overall
population
shrinks by morethan 20%.

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Japan became an ‘aging’society in 1970 when its elderly
population reached 7%.

20
15
10
5
0

1970

1975

1980

1985

Source: Statistics Bureau, Ministry of Internal Affairs and Communications
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CH I B A U N I V E R S I T Y

1990

1995

2000

2005

2010

2015

I N S T I T U T E F OR G L OB A L
PR OM I N E N T R E S E A R C H
Chiba University is cultivating globally prominent research groups in three areas: thehumanities and social sciences, science and engineering, and the life sciences. Throughconcerted efforts in these research areas — referred to as the Triple Peak Challenge — theuniversity will promote innovation that paves the way for the next generation.
The Institute for Global Prominent Research (IGPR) was established in 2016 as aframework for the implementation of Chiba University’s research strategy and its long-termgoal of creating research groups that are novel, original and full of potential, and willplay a key role in research at the university. IGPR is promoting research at two levels:
the Research Division, which cultivates globally excellent research groups and forms
world-prominent research bases, and the Next-generation Research Incubator, which
nurtures the university’s prospective priority research areas. The Management Divisionevaluates and selects research projects, and allocates strategically aggregated researchresources based on each group’s requirements and an evaluation of their progress.
Through the establishment of IGPR, Chiba University hopes to contribute to society bycreating innovation and fostering prospective world-level researchers.

1-33 Yayoi-cho, Inage-ku, Chiba-shi,
Chiba 263-8522, Japanwww.chiba-u.jp
http://igpr.chiba-u.jp