A spherically-grown nerve cell. Behavior of the target gene can be observed
from synapses protruding from the sphere’s outer surface. Axons are labelled ingreen and synapses in red.
Turn to page 6 to find out more about the research. (Photo credit: Ohtan group)Feature

iCeMS tour

Sliding shoji doors andsudare blinds add atint of the traditional
Japanese style.

with researchers
The facilities of iCeMS embody thegoal of the institute, which is an amalgamation of cell biology,chemistry
and physics. In this issue, Associate Professors Ken-ichiro Kamei,
Shuhei Furukawa and Hideki Hirori
guide your tour of iCeMS with theirknowledge of the institute.

Dr. Kamei

Dr. Furukawa

Dr. Hirori

iCeMS Main buildingEnter

Paintings are locatedthroughout the facility.

Followme!

The main building of iCeMS is
located right in front of the Kyodai
Seimon-mae bus stop (at themain gate of Kyoto University).

1st floor Courtyard
The shrubbery at the center, planted
to depict a cell, symbolizes iCeMS.
The wisteria and cherry tees blossom
in the spring.

1st
floor

2nd floor
Shared laboratory /common equipment room
The institute encourages the shared useof equipment, an economical measurethat helps create new ideas through casual conversations between neighboringgroups. This is an example of efforts
made by iCeMS to create a setting forcross-disciplinary amalgamation.

2nd floor Seminar room
This room is used to hold symposiums and otherevents. It is equipped for communications with
Kyoto University’s Uji Campus and a satellite officeat Gifu University.

1st floor
Researchers room
There are no partitions
separating the laboratories,
which facilitates discussion
and information exchange.
Extensive use of glass in thebuilding design creates an
expansive feel.

3rd

floor
3rd floor Cell culture room
Researchers handle ES and iPS cells in the
shoe-free incubation room. The incubator ismaintained at 37°C to approximate the environment in the human body. Researchers
conduct experiments in a biological safety cabinet, only putting their hands in the test cabinet.

2nd floor Exchange Lounge
iCeMS members can enjoy their lunches here,
viewing the street lined with gingko trees. The
lounge is used to hold meetings, concentrate on
individual projects, or, sometimes, have a party.

2nd

I can construct testing
apparatuses myself, even
if they are large. Threedimensional printers are very
useful for building testing
devices because they canmaterialize ideas quickly,
such as in the case of this cell
cultivation instrument.

You might hear the
piano played by a staff
member now and then.

floor

Here

A party is held on August
16 each year to view the
Daimonji bonfire.

2

Dr. Kamei is observing iPS cells
produced by Prof. Yamanaka.

ing

rch build

To resea3

Feature: iCeMS tour with researchers

iCeMS Research Building

1st
floor

Enter

2nd

2nd floor Chemistry lab
Dr. Furukawa pursues gas compression technology by chemistryof porous materials. When vaporized, one milliliter of liquid expands
to a volume greater than one liter.
A safe gas compression technology can improve fuel tanks ofnatural gas-fueled vehicles andpharmaceuticaldevelopment.
Among other technologies, he isworking on controlling vaporization of encapsulated chemicals inporous materials by providing asignal from outside.

floor

1st floor-2nd floor
Researchers room
The stairs at the center of theroom give an expansive feel andare intended to facilitate casualexchange of information between floors.

Welcome !

3rd
floor

Drs. Hideki Hirori (laser spectroscopy
and optical science) and Shuhei
Furukawa (coordination chemistry)guide you through the iCeMS researchbuilding. They share humorous
exchanges, even though they study in
different fields.

One of our favorite places
is between the researchbuilding and the projectlab. We often have lunchat the western-style table
and chairs placed here.

Researchers arrange
and decorate theirdesignated workspace
to inspire their creativity.

The meeting room is set up to allow
you to have discussions whenever
you want. The clear-glazed doors
facilitate transparency.

2nd
floor

Thank you!

MAP
Seifuso
GardenNorth
CampusHyakumanben

West
iCeMS Campus
Mainbuilding
Keihan Railway

Higa
Oji strshieet

The official language
used in iCeMS is
English. Foreign
researchers accountfor about 30% of all
researchers working
at the institute.

Exit

Faculty of
Medicine

iCeMS
Researchbuilding

Main Campus

YoshidaMinamiCampusMount
YoshidaJingu
Marutamachi

The rows of magnifying glass-like tools create a device that generates terahertz waves.

This apparatus, popular in the laboratory,
is commonly called a “microwave oven.” It
operates on the same principles as marketavailable ones. In several minutes it heats
liquids, which via other heat sources would
take hours. Different from common microwave ovens, it is built to be explosion-proof,
which means it is robust enough to preventthe container from scattering away in postulated explosions.

Kamo River

4

This apparatus is commonly known as a“glove box.” The user places their arms
into the box via the black gloves to work
while ensuring that the interior is isolated
from the surrounding air. The box is filledwith nitrogen or another inert gas.

Demachiyanagi

2nd floor Project Lab
Terahertz radiation consists of electromagnetic waves with a frequency
between radio waves and light (infrared) waves. The intensity of terahertz
waves developed by Dr. Hirori is the highest in the world. His laboratory
betters its record each day and accepts tour applicants from across the globe.
Advances in terahertz wave generation technology are expected to lead tothe discovery of new phenomena that will enable faster and more energyefficient computers. Moreover, novel products can make use of the newphenomena, and this technology can assist technical innovation in security
systems to, for instance, detect hazardous substances and illegal drugs at
airports. He is also meeting the unprecedented challenge of finding out what
will happen when cells meet this range of electromagnetic radiation.

3rd floor Biochemical system laboratory
Biochemical science laboratories are far
quieter than chemical science laboratories,
which create considerable ventilation noisefrom the release of vaporized chemicals.

Faculty of Kyoto
Pharma- University
ceutical Hospital Marutamachi
Sciencestreet5

Interview

iCeMS Frontrunners

1

As Wang talks about the inner working of the brain, her eyes light up. “The human memory is a big
mystery. The experiences and knowledge we accumulate as we age eventually shape us as individuals
distinct from one another.” Her passion, or more like obsession, for the brain’s ability to memorize
information and experience began in her late teens. Wang continues to push the limits in the study oflife sciences because she sees vast potential for new methods of treatment that can help this generationand those to come.

“Reversing the brain damage”
to treat mental diseases
Dan Ohtan Wang
iCeMS Kyoto Fellow, Assistant Professor
The human brain is made up of
several thousand-billion brain cells,
each nerve cell with an average ofa few thousand synapses that form
an intricate network responsible
for learning and memory. Wang’s
research explores how these synapses
function on a molecular scale inmemory formation and preservation.
Dan Ohtan Wang
Born in Shenyang City of Liaoning Province, China. After
graduating high school in 1994, she entered the schoolof Bioscience and Biotechnology at the Tokyo Instituteof Technology in Japan. In 2000, she studied Cellular
Molecular Biology at the Univ. of Alabama. In 2002, shetransferred to USC and received her PhD in 2004. From
2005, she worked as a postdoc at UCLA, as a JSPS
Postdoctoral Fellowship for Overseas Researcher at
RIKEN, and as an Assist. Prof. at iCeMS since 2011. In
2015, her research project was selected by the Hirose
International Scholarship Foundation as the first project tobe funded in neuroscience.

6

Dreaming of becoming
a doctor“My mother comes from a lineageof doctors. I heard that my grandfather
was famous in his village for his
expertise in both Western medicine
and Chinese traditional and herbal
medicine.” She was inspired by her
family to pursue a profession where
she could help people. “I enjoyedlearning about biology and healthin school. I thought, maybe this is
the direction I should be headed…”
Wang was about to enter middle
school when she had the idea ofstudying abroad in Japan. Back then,her hometown, Liaoning Province,
had close to zero foreigners. One day

a doctor. “Back then, only Japanesenationals were eligible to attend
Japanese medical schools. I had tochoose between becoming a doctor in
China or studying abroad, and I chosethe latter.” She ultimately picked auniversity program that was close
to medicine, the Interdisciplinary
Graduate School of Science andEngineering at the Tokyo Institute ofTechnology. An emotional teenager
traveling overseas for the first time,“everything was so different from
China,” says Wang. “Tokyo is a
Six years of classes,
city full of exciting information andexperiments, and working
commercial goods. It’s still a special
part-time jobs
place for me.”Wang’s first college choice was
In her undergraduate degree,
one in Japan. She attended a language
Wang studied immunology toschool for three years to prepare for
explore the world of genomes under
exams but still dreamt of becoming
Prof. Akira Kudo. The theme of her
graduation thesis was
genomic rearrangement
Probe
and the somatic hyper
mutation in immune
cells. The human bodyIn the absence
When there is
produces antibodies forof target RNA
target RNA(fluorescence-off)(fluorescence-on)
all antigens that invadeit, and this process,RNA labeling technique in live brain tissue of mice, as develon a molecular level, isoped by Ikumi Omoto of the Ohtan group. Fluorescent probes
are introduced into the cell through injection and the application a rearrangement andof electric current pulses to label target RNA in live tissue. Thisfacilitated mutationing
new labeling technique allows us to observe localized RNA inprocess of the genome.
the cells of live tissue.
a gift of paper cranes was sent to herfrom a Japanese elementary school.
“They were breathtakingly beautiful.
I began to take an interest in Japanand had to find out more about thecountry.” Around the same time,
watching Japanese movies on TV
became her new obsession. “‘Izu no
Odoriko (The Dancing Girl of Izu)’
was my favorite. I was a huge fan of
the lead actor.” Soon she longed tovisit Mt. Fuji, which appeared as alandmark in TV shows.

Dr. Belinda Goldie studies specific RNA
regulators in human nerve cells.

“The genome has this incredible
ability to deliberately mutate toincrease variation. If we can discover
how this works, we can understandhow to treat particular illnesses.”
However, learning experimental
techniques and conducting research
was an arduous experience for her.
Rent and monthly bills ate away mostof her scholarship money. Lab workand part-time jobs occupied mostof her free time. After finishing hermaster’s degree, Dr. Kudo suggested
studying in the United States so she
could focus more on research. “Dr.
Kudo was extremely supportive inmany aspects, not just my research
but also the practical side of life.”

Visiting multiple labs
in America
At age 24, Wang joined Prof. Peter7

Interview: iCeMS Frontrunners

Barrows’ lab to make a fresh start at
the University of Alabama, where she
studied genome reorganization andmutation mechanisms. However,soon after her move, major discoveries
in her field were published in thejournal, Cell. “I felt a sense of despair,that there was nothing left for me todo. Looking back, those two papers
only revealed a small part of theimmune functions. But back then, I
couldn’t help but feel depressed.”
She picked herself up by building
her confidence in the field of research.
“In America, where people of many
cultures and races coexist, there are
no given standards of how a person
should be. I felt free to be who I was.
I was treated the same as everyoneelse.” What followed numerous lab

visits was her newfound curiosity
toward neuroscience. “The world we
see and the world projected in thebrain, are they identical? And how
can two different people recognize
the same color? I was intrigued bylectures that addressed simple but
fundamental questions like this.”Rewiring the brain’s neuralcircuit subconsciously
through experience
Wang transferred from the
University of Alabama to USC tostudy psychiatry, after learning thata person’s emotions or wakefulnesssleep conditions are controlled by
the chemical balance in the brain.
“I have been studying transportermolecules, or neurotransmitters(brain hormones) like serotonin anddopamine, since I was in graduate
school. I wanted to understand themolecular mechanism of how we feel‘happiness’ is influenced by memory.”
Wang looked at the brain’s
memory storage process, or “episodic
memory”, a subconscious rewritingthat occurs in the brain’s neuronal
circuit every time a person experiences something new. This inspired hercurrent research, which may lead tobetter treatments for mental diseases.
“Molecular biology is my expertise…
I was certain that this was the fieldI could shine in.” According toWang, by seeing and analyzing
genomic activity in a living brain’s
neural pathway, researchers can begin
questioning where and how memory

is being stored. Discovering thefunction of RNA (ribonucleic acid)and unveiling memory function seem
like two dots that simply do notconnect. “My job is to ‘bridge’ theiCeMS
Researcher Q & A❶ Your favorite spot at iCeMS?

The iCeMS research building in
the fourth floor joint laboratory.
From the window the north-facing
Kitayama and Hiei look great.

❷ Please tell me what you are fussy

about at work?
I want as much as possible toempty what is in my head. I try not
to accumulate work. I immediately
reply after reading an e-mail. I do
not open the same e-mail twice.

❸ How do you spend lunchtime?

Incommunication
withlabmembers or research discussions
with colleagues.

❹ What are your moments of relief?

Looking at the sleeping face of mydaughter.

❺ What is your creed?

Do you have a desk motto?
You must do the thing you think you
cannot do. —Eleanor Roosevelt❻ What surprised
you, coming toJapan?
On my first visit toJapan in 1994, I was
surprised at theconvenience store
and the phone box.

ab

Primary cultures of neurons taken from mice hippocampus. Activity in the cell can be observed by dyeing the neurons. Dendrites are colored in green,
and RNA regulatory proteins are colored in red. You can see that RNA regulatory proteins are localized in the nucleus in a, and in the cell body in b.

8

The first working day
at iCeMS. That day
was also my daughter’s
entrance ceremony ata kindergarten.

divide. Understanding RNA is nota cure-all, but it can certainly help
develop a hypothesis. We needed ahook, and this was it.”Seeing the world throughdifferent colored glasses
Wang returned to Japan in 2010
to join Riken at Wako, Saitama
prefecture. She resided for a year
at the Organic Synthetic Chemistry
Lab to make probes, or “illumination
markers”, that help visualize RNA
activity in a living brain. When seenfrom a chemist’s point of view, RNAlooked completely different. It wasalmost like seeing a magic trick forthe first time. “The special probes
instantly make the RNA shine when
injected into the cell.” After practicing
with various tools since her days in
UCLA, seeds started to bear fruit in
Kyoto. Approached by Dr. Nakatsuji,
founding director of iCeMS, at an
iCeMS seminar, she soon became incharge of a research group. Japan’s
strength in chemistry helped produce
many groundbreaking discoveries andconsequently Nobel Prize winners,
and Kyoto University is one of thebest universities in Japan. “I felt thatmy research could only be achieved inJapan. I am experiencing a life that
I could never have imagined before

arriving here.”

Using the mechanism oflearning and memory
The truth is, many people sufferfrom mental illnesses in the modernage, and plenty of previous studies
prove that these illnesses are related
to patients’ gene abnormalities.
Surprisingly, the only effective treatments that exist are medication andelectric shock, despite treatments
for mental diseases being around forsome time. Eliminating side effects
of drugs have proven difficult since it
leaves the entire body vulnerable tothe drug’s effect. There are ways todirectly control the chemical balanceof the brain and modify the genome,
but Wang suggests we tap into ourinnate functions, such as memory andlearning. The brain’s neural network
is being constantly overwritten byexternal signals. By taking advantageof the brain’s “reversibility” we canfine-tune the expression pattern ofthe genome just by changing thesurrounding environment. “If theneural network is rewritten by gene
expression, behavior can be altered,”says Ohtan. Antidepressants promote
the production of serotonin and help
deliver them to the body. “The humanbrain is not a flask. To treat the target
9Interview: iCeMS Frontrunners

area, it is far more effective to use thebrain’s delicate import system. Why?
Because the brain has the inherent
ability to restore itself.”
She is experimenting on micefor her project on targeted RNA
illumination. “One day I want todevelop probes that can be used in
hospitals and clinics,” says Wang. “Myteenage dream of becoming a doctor
is connected to where I am now.” Shesays iCeMS has provided a perfectenvironment where researchers acrossdisciplines can engage in discussions
that lead to innovation. Wang’s
research happens to be a concoctionof life sciences and technology. “I
discovered that there are no limits tofusing disciplines at iCeMS.”

Challenges ofleading a teamWang is the head of her teamof ten staff, all working toward one
goal: finding links between genes
and brain plasticity. However, theprocess is a constant tug-of-war,
and multiple experiments collide.
Research background and interests
vary from person to person, and theideas and interpretations of results
largely influence the overall directionof the project. Small differences canlead to interesting developments or
10

digress from the originalplan.
“I struggle tofind a balance between
exercising the rightamount of leadershipand respecting the spaceof each staff. Needlessto say, leadership isessential in order toproduce maximum results fromprojects that are limited in time andresources. I need to communicate
and manage staff effectively. Staff
members that are actually doing theexperiments are one step ahead in
the future by coming into contact
with the latest data, and I am in thepast waiting for them to report tome. I want to minimize this timelag. Until now, I was fine with having
one hard drive, but I am learning tocompartmentalize according to therole that I play.”

Family time isjust as important
Wang steps into the office before
nine a.m. She begins her morning
routine with a cup of coffee andflipping through science magazines
such as Nature, Science, Cell, andNeuron. “I enjoy this time a lot,” says
Wang. After the lab members arrive,
she attends meeting, checks e-mails,

iCeMS in brief

What’s new?

Research Highlights
iPS cells used to correct
genetic mutations that cause
muscular dystrophyand finishes other administrative
tasks until noon. During lunch she
takes the time to interact with her
lab members. “Research funding
applications, writing papers, updating
the group homepage… I am always
writing. Around six p.m. I take off
to pick up my daughter. I eat dinnerwith my family. We even play games
together. My daughter turned nine.
I want her to grow up so she can be
my scientist buddy [laughs].” Wang’shusband is also a researcher. Sameage, and at similar stages in theircareers, the couple often turn to eachother for support. “My little girlseems to have taken on some of ourtraits. One day I came into work andopened my bag. There was a notewith a message that read ‘good luckwith your paper.’ Around the timeof the Nobel Prize Announcement,
she asked how many Nobel Prizes
I’ve gotten so far. In a way, she hashelped a lot; she gives me energy.”

Assistant Professor Akitsu Hotta’s teamrevealed that induced pluripotent stem
(iPS) cells can be used to correct genetic
mutations that cause Duchenne muscular
dystrophy (DMD). The research, publishedin Stem Cell Reports, demonstrates how
engineered nucleases can be used to edit
the genome of iPS cells generated fromthe skin cells of DMD patients.

Princess Maha Chakri Sirindhornof Thailand visits iCeMS

Expression of dystrophin in skeletal muscle cells
by iPS cells derived from patients

Original technique to successfully
blend polymers
A team of researchers led by Dr. Susumu
Kitagawa has developed a new techniqueto successfully blend different types ofpolymers for the first time. This finding,published on July 1st in Nature Communications, will significantly contribute to
the development of novel smart materials.

On April 20, Her Royal Highness Princess
Maha Chakri Sirindhorn of Thailand
and a Thai delegation visited iCeMS.
Princess Sirindhorn discussed with core
members the future of iCeMS’ role as a
global hub for research collaboration.
After presentations, the Princess wasgiven a lab tour to introduce researchusing state-of-the-art equipment.

By using porous materials as a mold,this technique completely mixes thepolymer at the molecular level which
has not been done before

KP-1 probes to identify Human iPS
cells on sale from June 1“Learning Lounge” series
available online

A chemical probe that becomes selectively
embedded in human embryonic stem(hES) and induced pluripotent stem cells,
discovered by Professors at iCeMS,
are manufactured and sold by Goryo
Chemicals. The probe could be used
to help scientists and doctors selectcultivated cells for use in efficient and safe
regenerative medicine treatments.

The “Learning Lounge” features young
scientists who, in 20 minutes, deliver apresentation to persuade any listener,
even those without a scientific background, why their research area is important to the world. The series can beviewed on the iCeMS YouTube channel
and from the iCeMS website.
http://www.icems.kyoto-u.ac.jp/e/rsch/ll/

Collection of shiny iPS cells

11Groundbreaking research at the border between Materials and LifeAt iCeMS, we develop new insights into theprinciples of life that distinguish living things from
non-living things. We harness these ideas to create
bio-inspired super materials and devices that will
revolutionize health-care, medicine, industry and theenvironment to create a sustainable world for us all.
Whilst much of the work we do here at the Instituteis pure science, we are absolutely certain that our
research, combining high-level chemistry, cell biology
and physics at the border between materials and life,
will meaningfully impact the world in which we live.

Porous materials controllingbioactive gases
Extracellularenvironment
Synthesized celladhesion substrates

NucleusControllingcell membrane
function byphotoinduced
materials
Cell membrane

Cell biology

Chromatin

Medicine

Compounds for
specific gene
expression

Chemistry

Environment and Energy

Help us grow
Generous gifts from donors like you provides

Individuals

the financial and moral support needed tocontinue to develop this research at the cuttingedge of modern science. We are not merely
content to improve existing technologies, but● Managing a world-class research center

Donations
Corporations/Organizations

seek to affect a paradigm shifts in the way

http://www.icems.kyoto-u.ac.jp/e/fund/Vol.1
2015 December● Producing promising scientists of

the next generation

science may benefit humanity.

iCeMS
Our World, Your Future● Creating a unique new research field

Production Institute for Integrated Cell-Material Sciences at Kyoto University, Yoshida
Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan
Phone: +81-(0)75-753-9755 | Fax: +81-(0)75-753-9759
E-mail: info@icems.kyoto-u.ac.jp
Homepage: http: //www.icems.kyoto-u.ac.jp
Production/cooperation: Kyoto Tsushinsha Press, Design: Takayoshi Nakasone