LETTERINSTITUTE FOR ADVANCED RESEARCH

March 2024 Vol. 22

Special interview
Onomatopoeia allows looking back to the origin of language and forward tointerdisciplinary collaborations
1___ Kimi AKITA

2

Like a painter of unique works, Dr. Matsubayashi explores the worldof peptide hormones with unparalleled technological skills.
___ Yoshikatsu MATSUBAYASHI

3

Meeting people, Learning societal needs, and Arranging new“Chemical Reactions”___ Mizuki TADA

Research Highlights

Uncover the function of epigenetic regulation in plants nitrate nutrition stresses
and its memory / Fanny BELLEGARDE
Topology in Superconducting Proximity Effects / Satoshi IKEGAYA
Let the fat out of the bag: Revealing the role of adipose tissues as minionsof ovarian cancer / Shohei IYOSHI
Art in modernity and Diderot's philosophy / Keiko KAWANO
Understanding the dynamics of the large-scale structure of the Universe / Shohei SAGA
Revealing autolytic mechanisms of sieve element differentiation / Yuki SUGIYAMA
Integrating genomics and biophysics to comprehend tauopathy / Koyo TSUJIKAWA
Exploring the Potential Applications of Biocatalysts / Atsushi USAMI
Observation of Mg-intercalated GaN Superlattice Nanostructures / Jia WANG

22March 2024

LETTERI N S T I T U T E F O R A DVA N C E D R E S E A RC H

The Showcase for Advanced Research andDevelopment of Research Person of Talent− Voyage for New Standards of Academia −The Institute for Advanced Research ( IAR ) , Nagoya University, was established in 2002
to promote the world’s top-level research, and to contribute widely to society through the

CONTENTS

03

Special interview
1

Onomatopoeia allows looking back to the origin of language and forward
to interdisciplinary collaborations___ Kimi AKITA

2

Like a painter of unique works, Dr. Matsubayashi explores the world of
peptide hormones with unparalleled technological skills.
___ Yoshikatsu MATSUBAYASHI

3

Meeting people, Learning societal needs, and Arranging new“Chemical Reactions”___ Mizuki TADA

outstanding research outcomes. The IAR is among the first such organizations established inJapanese universities with the first director Prof. Ryoji Noyori. The IAR has since maintained
promoting especially in Nagoya University’s pure research from a broad perspective thattranscends the conventional disciplinar y boundaries. Today, the mission has expanded toinclude the promotion of academics at the Nagoya University, support for excellence in research,developing the next generation of central research and researchers, and conducting international
research exchanges. The IAR aim to promote exploring the new research field as worthy of oneof the world's leading research universities. We have been hosting IAR lectures and seminars,
including the Nagoya University Lectures, delivered by eminent researchers, to whom thepresident of Nagoya University awarded special lectureship. The IAR has been also serving asa steering committee member of the University-Based Institutes for Advanced Study (UBIAS)
which is the international network of the other institutions of this sort around the world.
Furthermore, the IAR has been encouraging early-career researchers to be the next generation’s
leaders through the Young Leaders Cultivation ( YLC ) program and Young Researcher Unit.

15

IAR Information

21

Research Highlights
Uncover the function of epigenetic regulation in plants nitrate nutrition stresses and its memory/ Fanny BELLEGARDEAs Nagoya University aims to become one of the world's leading research universities in theframework of Tokai National Higher Education and Research System, the IAR aims to further

Topology in Superconducting Proximity Effects / Satoshi IKEGAYA

expand the functions as a hub for research information and human resources, and as the showcaseof research, research activities, and the development of research personnel. I keenly look forward

Let the fat out of the bag: Revealing the role of adipose tissues as minions of ovarian cancer/ Shohei IYOSHI

to your continued support with your guidance and encouragement for the IAR.

Art in modernity and Diderot's philosophy / Keiko KAWANO
Understanding the dynamics of the large-scale structure of the Universe / Shohei SAGA

Kunio AWAGA
Director of Institute for Advanced Research

Revealing autolytic mechanisms of sieve element differentiation / Yuki SUGIYAMA
Integrating genomics and biophysics to comprehend tauopathy / Koyo TSUJIKAWA
Exploring the Potential Applications of Biocatalysts / Atsushi USAMI
Observation of Mg-intercalated GaN Superlattice Nanostructures / Jia WANG

30

IAR People

34

Special Feature

Director

Kunio AWAGA

Cover Picture :MATSUBAYASHI LAB's Representative
Research on Nature Plants 7, 310 (2021)

Special Interview 1 | Kimi AKITA

Nevertheless, he boldly explored this topic, which led to the book
Gengo no Honshitsu: Kotoba wa Doo Umare Shinka Shita ka,(2)which he co-authored with Dr. Mutsumi Imai. While quoting
from the book, the next section will give some examples of how
language begins with highly iconic words such as onomatopoeia
and then gradually loses iconicity as it becomes systematized.

SpecialInterview

1

Kimi Akita
Associate Professor, Graduate School of Humanities, Nagoya University
Dr. Akita is the author of Onomatope no Ninchi Kagaku (“Cognitive Science of Onomatopoeia”) and co-author of Gengono Honshitsu: Kotoba wa Doo Umare Shinka Shita ka (“The Nature of Language: How Language Was Born and Evolved”).
The latter is a bestseller with a circulation of over 200,000 copies. While focusing on onomatopoeia, Dr. Akita also
conducts cross-disciplinary research.

Although iconic, onomatopoeia are not primitive or immature.
They follow systematic patterns. For example, “sara-sara” may be
an adverb as in “A brook is running sara-sara (smoothly),” or an
adjective as in “Your skin is sara-sara (smooth).” Intriguingly, theaccent pattern differs between the two cases. When the word isused as an adverb, its pitch pattern is high-low-low-low. When it
is used as an adjective, its pitch pattern is low-high-high-high. The
same holds true for other adverbial and adjectival onomatopoeia.
Onomatopoeia have attracted particular attention since thebeginning of the 21st century. Look at the two figures drawn
below. Now, if you had to name one of them “bouba” and theother “kiki,” which one would be “bouba” and which would
be “kiki”?

Onomatopoeia allows looking back to the origin of
language and forward to interdisciplinary collaborations______ Encounter with the study of onomatopoeia and thedevelopment of the field
Dr. Akita used to study English linguistics, with special attention
to expressions of emotions. “Worried,” “excited,” and “surprised”
may be expressed in Japanese with the onomatopoeia “kuyokuyo,” “waku-waku,” and “bikkuri,” respectively. Through a close
examination of the two languages, he noticed that Japanese has
many more types of onomatopoeia than English. Onomatopoeia(termed “ideophones” in linguistics) attracted his interest, but
the field is often viewed as peripheral in the realm of linguistics.
At first, he thought he would work on onomatopoeia only forhis master’s thesis. Before he knew it, however, he came to devotehimself to the field for 20 years.
“What motivates me to keep working on onomatopoeia,” Dr.
Akita remarks, “is their seemingly chaotic behavior. They are
impressionistic and are not apparently linguistic, but on a closer
look, they follow certain patterns.”
We use onomatopoeia every day but know very little about
them. Examining them from a linguistic perspective allows
finding numerous hidden regularities and commonalities
03 | IAR LETTER | March 2024with other languages, which fascinates Dr. Akita.
Onomatopoeia, a category of words that express sounds, states,
and actions, is particularly familiar to Japanese speakers. For
example, “sara-sara,” “gotsu-gotsu,” and “sorori-sorori” describe
a rustling sound, a hard, rough surface, and slow, quiet steps,
respectively. It is not easy to define onomatopoeia, but experts
consider them to be “iconic” words, which here mean symbols
that directly reflect sensory information. “(^_^)” is a Japanese
icon that visually depicts the characteristics of a smiley face.
Similarly, onomatopoeic words such as “meow” and “bow-wow”
can be considered as iconic words that auditorily imitate thesounds of cats and dogs.

There are linguistic sounds that match spiky figures and those that go well withrounded figures. Please note that the figures shown above were drawn by theauthor of this article with reference to Fig. 7 in the paper published by V. S.
Ramachandran and E. M. Hubbard in 2001.（1）Interestingly, most people pick “kiki” for the left figure and“bouba” for the right figure in a wide range of languages. Visual
impressions and verbal sounds are two different types of sensory
information, but they are interconnected. This phenomenon iscalled the “bouba/kiki effect,” which was named as such by V.
S. Ramachandran and E. M. Hubbard in a paper published in
2001.(1) When humans started using words, perhaps they might
have systematized them into language through the accumulationof such phenomena. It is difficult to prove this hypothesis, andthere are many competing theories on the matter. Nevertheless,the paper captured the spotlight at that time as a clue to theorigin of language.
Dr. Akita thinks that the bouba/kiki effect is closely related toonomatopoeia, in that it concerns the iconicity of visual andauditory information just as onomatopoeia do. As a naturalconsequence, he has been investigating the relationship between
onomatopoeia and the origin of language. The relationship isdifficult to prove because you cannot trace back the changes
in language over a hundred thousand years. Dr. Akita himself
confesses that it is somewhat scary to work on this huge issue.

（1）Ramachandran, V. S. & Hubbard, E. M. (2001). Synesthesia:
a window into perception, thought, and language. Journal ofConsciousness Studies, 8: 3-34.
（2）Gengo no Honshitsu: Kotoba wa Doo Umare Shinka Shita ka
Co-authored by Mutsumi Imai and Kimi Akita, Chuko Shinsho,
First edition published on May 24, 2023______ How are highly iconic words systematized?
“In fact, surprisingly many ‘ordinary words’ that we currently
do not consider to be onomatopoeic were once onomatopoeicwords” (p. 141). The language we use today did not suddenly
come into existence one day as a complete system. For example,
the onomatopoeic words “tat-tat” and “fuu” are said to be theorigins of certain ordinary words. According to Dr. Nakami
Yamaguchi, a leading researcher on the history of Japanese
onomatopoeia, “tat-tat” and “fuu” were joined with “ku,” anarchaic Japanese suffix making verbs, changing into “tataku”(hit) and “fuku” (blow), respectively. The onomatopoeia “kara”
and “ugui,” which transcribe animal sounds, were joined with“su,” a suffix that indicates a bird, becoming “karasu” (crow)and “uguisu” ( Japanese bush warbler), respectively. Through theaddition of affixes or through conjugation, many onomatopoeicwords were changed into ordinary words, allowing them to be
used as nouns and verbs.
Nicaraguan Sign Language is a famous example of the way
highly iconic words are systematized over generations. It attracts
the attention of researchers as an example of a language whosechanges were observed almost in real time in the modern age;they took place within the last 50 years.
Nicaragua, a Central American country, used to have neither
an education system for deaf children nor a standard sign
language. Sometime between 1970 and 1980, an environment
was developed for such children to study at school. The first
generation of these children created a sign language as a meansof communication, which was passed on to the next generation.
One of the changes that occurred during this process was “thedivision of gesture into elements, and the recombination ofthese divided elements” (p. 147). For example, when signing
the concept “rolling down,” first-generation children used ahighly iconic gesture that precisely portrayed the action visually.
But then, how would you sign a concept similar to “rolling
down,” say, “sliding down”? If you followed the same method,
you would have to keep creating and memorizing an infinite
number of signs so that you could convey small differences
between similar but different actions. To avoid this problem,
second-generation children divided the gesture “rolling down”
March 2024 | IAR LETTER | 04

Special Interview 1 | Kimi AKITA

into the elements “rolling” and “down,” and then combined thetwo to express “rolling down,” and the same way was used todescribe “slipping down.” Putting existing divided words back
together made it possible to efficiently express other concepts.
Nicaraguan Sign Language is now internationally recognized as
an official sign language.

“Rolling”＋“Rolling down”“Down”
Expressing both manner and direction
at the same time

Expressing manner and direction
separately and sequentiallyFirst generation

Second generation

Fig. 5-2: Change in Nicaraguan Sign Language from the first generation to the second generation

Gesture which at first precisely visualized a concept was later divided intoelements and then used in combination. Source: Gengo no Honshitsu: Kotoba
wa Doo Umare Shinka Shita ka, p. 150, Fig. 5-2.

A group of highly iconic Japanese onomatopoeic words show
traces of changes similar to those undergone by Nicaraguan
Sign Language. An example is the difference between “ban” and“batan.” Both express a single impact sound, but while “ban” canbe used for a variety of strong impact sounds such as a collisionor an explosion, the use of “batan” is usually limited to the soundof a flat object falling or shutting. In fact, the consonant /t/ in“batan” indicates hitting or contact, as in “dotan” (the soundof a heavy object falling), “goton” (the sound of a hard object
hitting against something), “boto-boto” (the sound of large drops
dripping), and “gotsun” (the sound of a heavy object hitting hardagainst something). The consonant /t/, which represents one of
the subdivided categories of strong impact sounds, has createddifferent meaning from “bashan” (the sound of fluid collisions),“bachan” (the sound of fluid hitting flat object), or “baran” (thesound of a bundle of thin objects unravels). Onomatopoeia arehighly iconic but systematic, as mentioned at the beginning.
The last topic to cover in this section is the question of why
onomatopoeia differs depending on the language or dialect.
First, for the understanding of this topic, guess what animal
is represented by all these words: “chako,” “tako,” and “guruu.”
Believe it or not, the answer is a cat. “Chako” is a Tohoku region
dialect term. In that region, “cha,” a tutting sound used to attracta cat, has been joined with “ko,” a suffix for something adorable,
making “chako.” While it remained “chako” on the Yamagata
prefecture ( Japan Sea) side of the region, on the Miyagi prefecture(Pacific) side, it changed in sound to “tako.” “Guruu” is a dialectterm of Kikai Island in Kagoshima Prefecture. It evolved as suchfrom “guru-guru,” the way a cat purrs. Many onomatopoeic words
are transcriptions of actual sounds made by objects, but they canbe completely different depending on which sounds of the objects
are transcribed. Differences in onomatopoeia between languages
05 | IAR LETTER | March 2024

is also attributed to the phonological system of the individual
languages. For example, in English, “brrr” is the transcription ofa shiver, while “vrrr” is that of a car engine sound. In contrast,
Japanese speakers do not distinguish between [b] and [v], andthey may not be able to accurately grasp the difference in nuance.
This book also argues that the cause of these changes lies in ourability to handle metaphors and metonymies. These are only
a few examples of the views the book presents from various
perspectives. You should definitely pick it up and read it.

______ New possibilities of onomatopoeia in crossdisciplinary research
Onomatopoeic words such as “zuki-zuki (throbbing),” “kiri-kiri(splitting),” and “chiku-chiku (tingling)” are useful and familiar
expressions you may use when explaining your poor physicalcondition. For example, a patient may tell the doctor s/he has a“chiku-chiku (tingling)” pain. A report shows that patients feelrelieved if the doctor repeats the same onomatopoeic word inagreement, in this example by saying, “I know it’s chiku-chiku.”
On the other hand, because of their highly subjective nature,
onomatopoeic words that describe physical condition are believed
to be difficult to associate with specific symptoms, and doctors
find it hard to know how to handle these words. There is room
for research into onomatopoeia in medical settings, but much lessknowledge has been accumulated so far than you may think.
“It used to be believed that onomatopoeic expressions were vague
and varied so much from person to person,” Dr. Akita remarks,“but my study has suggested that inter-personal variability may
not be as great as we have expected.”

オノマトペの沼へようこそ！過去をさかのぼれば言語の起源、
未来を見通せば異分野への応用が見えてくる秋田 喜美

名古屋大学大学院
人文学研究科 人文学専攻 准教授

著書に、単著『オノマトペの認知科学』、共著『言語の本質-ことばはどう生まれ、進化したか』がある。
後者は20万部を超えるベストセラーとなっている。
オノマトペを中心としつつ、分野横断的な研究も展開している。

実は奥深いオノマトペの法則性と言葉の成り立ち「オノマトペの研究を続けている理由は、その不思議さですね。
直感的で言語らしくないのに、よく見ると法則があります」
オノマトペとは、「さらさら」、「ごつごつ」、「そろりそろり」といった、音や状態、動作などを表現する言葉で、特に日本語ではなじみ深い。
その定義は一筋縄にいかないが、「“アイコン”的な言葉」
といった捉え方がある。
ここでの“アイコン”とは、感覚情報を直接的に写し取った記号のことをいう。
たとえば、「(^_^)」
は人の笑顔の特徴を視覚情報として写し取ったアイコンである。
同じように、「にゃーにゃー」、「わんわん」
といったオノマトペはそれぞれ、猫と犬の鳴き声を聴覚情報として写し取ったアイコン的な言葉と考えることができる。
また、アイコン的ではあるものの、原始的というわけではない。
体系化された法則が見られるのも特徴だ。
たとえば、
「小川がさ
らさらと流れる」と言う場合と、「 肌がさらさらだ」と言う場合では、「さらさら」のアクセントが変わるのに気づくだろうか。
「さらさ
ら」
のあとに
「と」
がつく場合は、「さ⤵らさらと」、
「だ」
がつく場合
は、
「さ⤴らさらだ」となり、これは他のオノマトペでも同様だ。

「バチャン」、「バラン」とは異なる意味合いを表し分けている。
また、「実は、現在私たちがオノマトペとみなさない
『普通のこ
とば』
（一般語）
の中には、昔はオノマトペだったものが驚くほどた
くさんある」(p.141)とあるように、私たちが使う言葉は、
ある日突然完成された体系として現れたものではない。
身近なものでは
たとえば、「タッタッ」、「フー」という擬音語はそれぞれ、ある単語の語源になっているそうだ。
オノマトペの歴史研究の第一人者である山口仲美さんによると、古語で動詞化するための接辞「く」を末尾につけて、「たたく」、「ふく」
へ変化したという。鳴き声を写す
擬音語「カラ」、「ウグイ」に、鳥であることを示す接辞「ス」
をつけて、それぞれ「カラス」、「ウグイス」となる。
オノマトペを名詞や動詞として使うために、接辞をつけたり活用させたりして一般語とする変化が多くの単語で起こっている。

身近なオノマトペに秘められた分野横断研究の可能性「ズキズキ」、「キリキリ」、「チクチク」
といったオノマトペは、
自分の体調不良を表現するときに便利でなじみ深い言葉だ。
また、患者の「チクチク痛みます」に対して、医師が「チクチクしますよね」と同じオノマトペで同意を返すと患者は安心する、という報告もあるそうだ。一方、主観性の高いオノマトペで表現する身体情Onomatopoeia, which are nothing new and have always beenused casually, are actually part of language in themselves with
their own set of meanings and system. Digging into them deeper
may enable you to unearth hidden possibilities.
“By verbalizing your sensation, you can organize it, become moreaware of it, and share it easily with others,” Dr. Akita points out.
“Onomatopoeic words may be difficult to handle at times, but
I am sure they have positive aspects and, if used properly, areapplicable to medical care.”もつ。意味が細分化された子音/t/を用いることで、「バシャン」、

報は症状との紐づけが難しく、扱いが難しい言葉とも考えられている。
こうした医療場面でのオノマトペは研究の余地があるが、今まで積み重ねられてきた知見は意外と少ない。
「オノマトペの表現は漠然としていて個人差が大きいのではな
いかと見られていました。実際に調査してみると、個人差は予想していたほど大きくはないようです」
秋田さんと今井むつみさんによる著書『言語の本質-ことばはでは、オノマトペの体系的な特徴や、どう生まれ、進化したか（1）』オノマトペがアイコン性を失い汎用性の高い言葉へ変化していく
道筋がいくつも紹介されている。
たとえば、
「バン」
と
「バタン」
の違いを考えたことがあるだろうか。
どちらも共通して一つの衝撃音を表しているが、「バン」はぶつかった音や爆発音など多様な強い衝撃音に使える一方、「バタン」は平面的な物体が倒れたり閉まったりするときの音に限定して使う。実は、「バタン」に含まれる子音/t/は、「ドタッ」、「ゴトッ」、「 ボトボト」、「ゴツン」のように打撃・接触を表す役割を

身近でいつも何気なく使ってきたオノマトペも、意味と体系をもつ言語だ。深堀りすることで、秘められた可能性を探し当てることができるかもしれない。
「感覚を言語化することで整理ができます。そうするとその感覚を自覚できるようになるので、情報共有もしやすくなります。
ときに扱いづらさもあるかもしれませんが、オノマトペによる痛みの表現には良い面があるはずなんです。
そういう意味で、医療への応用も可能かもしれないですね」（１）『言語の本質-ことばはどう生まれ、進化したか』

今井 むつみ(著)／秋田 喜美(著)／中公新書／初版刊行日2023年5月24日

March 2024 | IAR LETTER | 06

Special Interview 2 | Yoshikatsu MATSUBAYASHI

Things did not end there. Mass spectrometry showed that thesequence weighed 846, which was 160 more than five aminoacids. This fact led to the discovery of the structure of thesequence: a sulfate group with a weight of 80 was attached to
the first and third tyrosines.

“Ideas spread in an instant, but skills cannot be easily copied,”
Dr. Matsubayashi explains. “Researchers need both ideas andskills, but I believe that skills are just as important, if not moreso, than ideas.”

SpecialInterview

Conceptual diagram of the peptide hormone PSK with sulfate groups attached2

Yoshikatsu Matsubayashi
Professor, Department of Biological Science, Graduate School of Science, Nagoya University
Dr. Matsubayashi made the world’s first discoveries of plant peptide hormones and their receptors in succession, with hisfindings being published in many renowned academic journals, including Science. He continues to lead the field of expertisewith unique ideas and skills derived from his knowledge of both chemistry and biology.

Like a painter of unique works,
Dr. Matsubayashi explores the world of peptidehormoneswith unparalleled technological skills.
______ How do researchers develop their originality?
In 1996, Dr. Matsubayashi made the world’s first discovery of
the plant peptide hormone PSK (phytosulfokine), one of thehormones essential for communication between cells. Before
that discovery, a lot of attention in the research world had been
paid to the existence of a mysterious substance that promoted
cell proliferation. It was Dr. Matsubayashi who identified PSK
as that substance. Furthermore, at that time, peptide hormones
had been believed to exist just in animals, not in plants. Dr.
Matsubayashi’s discovery was so novel that peer reviewers of his
paper were skeptical about it. This achievement opened up a
new path for him as a researcher. At least it seemed so, but Dr.
Matsubayashi felt unsure.
He confesses, “Researchers of this type were likely to end up as
one-hit wonders.”
The laboratory that Dr. Matsubayashi belonged to was a groupof researchers known as “molecule hunter,” who identified active
substances in natural products. Their usual move was to pick aphenomenon discovered by other biologists and identify themolecules involved in it. However, there was only a limited
07 | IAR LETTER | March 2024

determine their structures. Finally, he synthesizes the molecules
and investigates the biological phenomena they cause. Dr.
Matsubayashi has established this process as his original researchstyle. It is in the reverse order to the normal molecule hunter’s
approach, which uses biological phenomena as a starting point.

number of notable phenomena to pursue, and there was fierce
competition in all of those research themes. It was not easy to
be the first to discover an unknown hormone, but such toughcircumstances did not discourage Dr. Matsubayashi. Whatshould such researchers rely on when making their next move?
His answer to this question is: “I should look back on the path I
have taken.”
PSK, the above-mentioned peptide hormone, is a small
molecule consisting of five amino acids linked in this order:
tyrosine-isoleucine-tyrosine-threonine-glutamine. As a pointof information, large molecules with a large number of aminoacids linked together are called “proteins,” while small moleculeswith a small number of amino acids linked together are called“peptides.” After examining all the conditions he could thinkof, including heat resistance, molecular size, and resistance toenzymatic digestion, Dr. Matsubayashi analyzed the peptide andsucceeded in determining the amino acid sequence it contained.

Conceptual diagram of amino acids contained in the peptide hormone PSK

After being translated from a gene into a molecule made up
of amino acids, it needed further modification in order tofunction. Because peptide hormones are small, they can easily
diffuse between cells, making it convenient for the cells to
exchange information. On the other hand, with a limited
number of amino acids, it is difficult to increase the variationof hormones. These molecular backgrounds are presumed to be
one of the reasons why post-translational modifications such assulfate groups are made, despite the use of energy.
“This is knowledge from organic chemistry,” Dr. Matsubayashi
remarks. “It is the world of chemistry.”Dr. Matsubayashi has always loved and studied both biology
and chemistry, and has utilized their knowledge in his research.
His skill in precisely determining chemical structures gave him agreat advantage. Furthermore, he incorporated genetic analysis,
which was cutting edge at the time, into his research. Dr.
Matsubayashi talks about “the perfection of molecule hunterthat I would aim for if there were such a thing.”“That would be to search for hormones from the molecular siderather than relying on biologists’ papers. The culmination of
my research is to use chemistry to explore phenomena that evenbiologists do not know about.”
This is the general process he follows. First, he reads genome
information to find candidate genes that are likely to become
hormones. After finding molecules that have been translated
from genes and modified, he performs mass spectrometry to______ His discovery of a receptor defied the common
wisdom in the world
If a hormone is compared to a ball, it needs a receptor, just as aball needs a glove.
“Looking back, I think I did a great job,” Dr. Matsubayashi
recollects. “After the discovery, I started to get recognized little
by little.”
At the time, the world was still skeptical about recognizing PSK
as a hormone. In fact, Science passed to publish his paper on
PSK at the time. The tide changed, however, in 2002, when theteam of Dr. Matsubayashi discovered the receptor for PSK. He
skillfully manipulated PSK to purify a PSK-binding protein,from which he derived genetic information, and he confirmedthat it contained information on sites commonly found inreceptors. Dr. Matsubayashi also confirmed that excessive
production of this protein promoted cell proliferation. The
protein proved to be the receptor for PSK. The results of thisstudy were published in Science, and Dr. Matsubayashi wasbrilliantly vindicated six years after the discovery of PSK.
The skills they developed in this finding were important for
subsequent research. Hormones and receptors exist in pairs.
If one side of a pair is identified, that is a powerful clue tofinding the other side of the pair. It is also possible to tell when
and where certain cells communicate, and this knowledge isuseful for elucidating specific mechanisms. For example, it waspredicted at the time that two molecules, CLV1 and CLV3
(clavata 1 and 3), were involved as hormones and receptors in
the continued production of the cells from which stem tips
derive their leaves and flowers. However, no one had been able
to prove it. Dr. Matsubayashi’s research group investigated thestructures of these two molecules and found that CLV3 is a
peptide hormone and that CLV1 is a receptor, and they binddirectly. His group had unparalleled momentum that no otherresearch group could match.
______ “Science is art”: Using unique skills, Dr. Matsubayashi
pursued the mystery of the peptide hormone PSY for 15 years

One of the mass spectrometers he regularly uses. By watching technicians whocame for repairs, Dr. Matsubayashi learned how to do simple repairs.

Of course, not all of his research projects went smoothly. One
March 2024 | IAR LETTER | 08

Special Interview 2 | Yoshikatsu MATSUBAYASHIIs there any unknown receptor that PSY binds to? Or does
PSY have another function? Then, Dr. Matsubayashi createdArabidopsis that could not produce PSY or its receptor. Again,
the roots grew longer than expected. This indicated that he was
missing something about the receptor. As a matter of fact, thereceptor had the ability to put a "brake" on growth when it was
not bound to PSY. When bound by PSY, the receptor releases
the brake, allowing growth. Accordingly, when the receptor is
missing, so is the brake, and in this case too, the roots grow long.

of his uphill struggles was research on the new peptide hormone
PSY (plant peptide containing sulfated tyrosine). Based on thecharacteristics including the post-translational modification of
sulfate groups, Dr. Matsubayashi made the discovery of PSY
and published it in 2007. He found that PSY promotes root
growth and cell proliferation, and that it has a role similar tothat of PSK, the first peptide hormone he discovered. However,
elucidation of PSY’s specific function did not go as smoothly
as expected. After a 15-year struggle, he finally got the whole
picture in 2022.
“I was uneasy about whether it was really a hormone,” Dr.
Matsubayashi recalls. “But at the same time, I was confident.
Although the function was still unknown, there was posttranslational modification, and the receptor had been identified.
These facts had helped me stay motivated for 15 years.”
When a hormone binds to its receptor, a certain function
is turned on. According to this idea, for example, when the
peptide hormone PSY binds to its receptor, root growth must
be promoted. In fact, Arabidopsis plants that cannot properly
produce PSY have shorter roots. In order to confirm the
hypothesis, Dr. Matsubayashi added artificially synthesized PSY
to them, and the roots grew long.

Conceptual diagram of PSY binding to its receptor. In this case, the roots
grow long.

So, what happens in the case of Arabidopsis plants that have
PSY but lack a receptor? The PSY has no receptor to bind to,so here again, there is no PSY-receptor pair. Despite this, theArabidopsis plants that lacked the receptor grew roots steadily.

Conceptual diagram of receptor deficiency. In this case, the roots grow long.

09 | IAR LETTER | March 2024

唯一無二の研究を描く―圧倒的な技術力で切り拓くペプチドホルモンの世界
松林 嘉克

名古屋大学大学院
理学研究科 理学専攻 生命理学領域 教授

植物ペプチドホルモンとその受容体を世界に先駆けて発見し続け、SCIENCE誌など有名学術誌への掲載多数。化学と生物両方の知見から生み出す独自のアイデアと技術で専門分野を牽引し続けている。

松林さんがはじめに所属していた研究室は、“もの取り屋”と呼ばれる研究一派。ほかの生物学者が見つけた現象をピックアッ

うように進まなかった。苦節15年。
その全容が明らかになるのは
なんと2022年のことだった。

プし、関与する分子を取り出すことがセオリーだった。
たとえば昔、「細胞増殖を促す謎の物質がある」と研究界で注目されていた。1996年、世界に先駆けて松林さんが突き止めた分子が、細胞同士のコミュニケーションに欠かせないホルモンの一つ、植物
Conceptual diagram of switching based on PSY-receptor binding. When thereceptor is not bound by PSY, it puts a brake on growth, and, as described
below, the cells prioritize stress responses.

Further genetic analysis revealed that when growth is put on
hold by the receptor, energy is preferentially spent to deal withstresses, such as high salt concentration, high temperature, ordisease. Under normal conditions, individual cells constantly
release PSY, which binds to the receptor in other cells, causing
the plant to keep growing. In contrast, when a cell breaks down,
the cells around it undergo a decrease in PSY concentration.
Then, the receptor in these surrounding cells is unable to bebound by PSY, preparing for stress responses rather than growth.
In other words, there proved to be a mechanism to detect thatsomething strange had happened in the event of a loss of “regular
reports” between cells.
Plants have steadily evolved to adapt to various environmental
changes, but such a sophisticated mechanism is beyond
our imagination. In this way, the research group led by Dr.
Matsubayashi uncovered another plant mechanism that could
almost be called artistic, as a result of the constant ambitious
efforts they had made while believing in the skills they had built
up by themselves.
Dr. Matsubayashi's research group has a variety of unique skills,
including the precise determination of molecular structures
based on chemical knowledge, genetic analysis, and the searchfor candidate molecules that are pairs of peptide hormones andreceptors. Mainly through research with members of his owngroup, Dr. Matsubayashi pursues what he is eager to know.
“To me, science is art, not business,” he argues. “If I compare
my team to a group of painters, we do not divide our work too
finely, like assigning the sketching to painter A and the coloring
to painter B. Each person works on what they want to depict,and they want to see it through to the end. We want to write an
academic paper that we would want to frame and display. If ourpapers were displayed anonymously, they would probably berecognizable as ours.”

ペプチドホルモンPSK（phytosulfokine）
だった。
しかし、
「私が
目指す、
もの取り屋の完成形があるとしたら」と松林さんは話す。
「生物学者の論文に乗っかるのではなく、分子側からホルモンを探す。
こんな現象は生物屋も知らないよ、というところに、化学をつかって攻め込むのが自分の研究の到達点と考えました」
昔から生物も化学も好きで両方学び、研究に生かしてきた。松林さんには、分子の質量を分析し、化学構造を精密に決定する技術があった。
「アイデアは一瞬で拡散します。
ですが、技術というのはそう簡
単に真似されません。研究はアイデアと技術の両方が大事です
が、技術はアイデア以上に大事だと僕は思っています」

植物は、環境変化ストレスや病害虫からの攻撃を受けたとき、成長に回していたエネルギーを防御に振り分ける必要がある。
組織的に動くためには細胞が、「危険が迫っている」と隣の細胞に次々と知らせなければならない。危機に陥った細胞がシグナルを出し、別の細胞がそれを受け取ることで伝達されるというのが一般的な理解だった。
しかし、壊れゆく細胞にそのシグナルを出す余裕があるだろうか。実は、危険を伝える方法にはもう一つある。ペプチドホルモン
PSYは定時連絡に必要な分子だったのだ。危険が迫っていない
通常時はペプチドホルモンPSYが各細胞から常に分泌され、一定の濃度が保たれている。
ところが、ある細胞が急に壊れると、その周辺の濃度が下がる。
つまり、定時連絡が途絶えたとき、「何か問
題が起きている」とほかの細胞が察知する仕組みがあったのだ。
植物は様々な環境変化に順応するよう進化を積み重ねてき愛用する質量分析計の一つ。修理に来た技術者のようすを観察して、今では簡単な修理なら自身でできるようになった

まずはゲノム情報を読み、ホルモンになりそうな遺伝子候補を見つける。次に遺伝子から翻訳された分子の質量分析を行い、構造を特定する。
そして分子を人工的に合成し、最後に関連する
生物現象を調べる。
これが大まかな一連の流れだ。生物現象を出発点とする”もの取り屋”の方法とは逆の順序。今では独自の研究スタイルとして確立し、松林さんの研究グループは世界が驚く研究成果を生み出し続けている。
もちろん、すべての研究が順調にいったわけではない。その一つが、ペプチドホルモンPSY（plant peptide containing
sulfated tyrosine）の研究だ。化学的なアプローチにより最初に発見したのは2007年。
しかし、その具体的な機能の解明が思た。
しかし、これほど巧みな仕組みを備えているとは驚きだ。松林さん率いる研究グループは、
自ら積み上げてきた技術への信頼を頼りに挑戦を続け、もはや芸術的ともいえるような植物の機構
をまた一つ、明らかにした。
松林さんの研究グループには、化学の知見をもとにした精密な分子構造の決定、遺伝子解析技術、ペプチドホルモンとそれをキャッチする受容体をセットにした候補分子の探索など、多様な独自の技術がある。知りたいことを、自身の研究グループを中心に追及している。
「サイエンスはビジネスではなくアートだと思います。絵描きにたとえるなら、下絵はあなた、色付けはあなた、のような過度な分業はしません。
自分が表現したいことを描きます。
自分が見届
けたくて、学術論文を書いて、額に飾りたいくらい。私たちの論文は、著者を隠されても、私たちのものだとわかると思います」

March 2024 | IAR LETTER | 10

Special Interview 3 | Mizuki TADA

imaging applied for medical diagnosis, parts that strongly
absorb X-rays appear white (e.g. bones), while parts with weak
X-ray absorption through the sample appear black. XAFS data
is measured by changing the energy of X-rays and recorded
X-ray absorption at each energy, which suggest us the amountof a particular element and neighboring atoms. It is a powerful
technique for identifying the local structures of catalysts.

beam with nano size, was developed at the large synchrotron
radiation facility SPring-8. She asked the collaboration using
the X-ray nanobeam and brought her samples whose catalyst
particles were spread on a support surface. She finally succeededin revealing the active structure of an individual catalyst particle
for the first time, using the X-ray nanobeam.

SpecialInterview

3

Mizuki Tada
Professor, Laboratory of Inorganic Chemistry, Research Center for Materials Science / Graduate School of Science,
Nagoya University
Studying the solid catalysts of inorganic materials, Dr. Tada works on both the synthesis of new catalysts and thevisualization of active catalyst structures and catalysis. She organizes various collaborative researches with industry such asfuel cell for automobiles and rubber tire.

Meeting people, Learning societal needs, and Arranging new“Chemical Reactions”______ Addressing longstanding challenges in catalyst research“Many catalysts have been used in modern society, but solid
catalysts are complicated. It is quite difficult to understand thestructures of active species in real catalysis.”
For examples, diamond has a crystalline structure in whichcarbon atoms are orderly arranged in a particular pattern. In
contrast, the structures of solid catalysts that Dr. Tada studies
are complicated and heterogeneous. A solid catalyst is composedof particles, whose sizes and structures are heterogeneous,and they are attached on a support material. However, thisheterogeneity is essential in real catalysis. How do they work?
Where do catalytically active sites locate? To understandthem on a fundamental level, it is necessary to utilize not only
synthetic approach but also techniques to “visualize” working
catalysts.
There are various approaches in studies on catalysts andcatalysis, and various knowledge and skills have been required,such as the synthesis of new materials, the developments ofreaction processes. In general, catalysts are prepared by the huge
repetition of synthetic trial-and-errors and catalyst tests. The
details of their active structures and catalysis are often found
11 | IAR LETTER | March 2024

（Left）The crystal structure of diamond.（Right）An image of a Ru3 complex
precursor and a Ru cluster catalyst prepared from the precursor. There arevarious Ru clusters in a variety of sizes and shapes, and they are dispersed on
the surface of a solid oxide support. (Dispersed Ru nanoclusters transformed
from a grafted trinuclear Ru complex on SiO2 for selective alcohol oxidation,
S. Muratsugu, M. H. Lim, T. Itoh, W. Thumrongpatanaraks, M. Kondo, S.
Masaoka, T. S. A. Hor, and M. Tada, Dalton Trans., 42, 12611-12619 (2013))

afterwards. Most of present catalysts currently used are still
black box without understanding their catalysis.
The laboratory Dr. Tada belonged when she started her
research activities focused on the developments of new
physicochemical methods for catalysis researches, anddeveloped measurement techniques to identify the local
structures of solid catalysts, called X-ray Absorption Fine
Structure (XAFS). This method uses high-energy hard X-rays
and the transmission and absorption behaviors of X-rays
depend on materials being irradiated. For examples, in X-ray

A typical XAFS spectrum of a copper compound. The horizontal axis
represents X-ray energy (unit: eV), while the vertical axis represents X-ray
absorption. Analyzing the sharp jump in the X-ray absorption (absorptionedge) and subsequent oscillations indicate bonding with neighboring atoms.

SPring-8, a large synchrotron radiation facility, located in the Harima Science
Garden City in Sayo-cho, Sayo-gun, Hyogo Prefecture, Japan (Copyright:
RIKEN)“When I was a Ph.D. student, I would like to synthesize newcatalysts and then out of necessity, I also became involved in
the characterization of catalysts. I’m always interested in what
synthetic researchers would like to know for their researches onmaterial synthesis.”______ Method to discern the individuality of catalyst“Catalyst composed of multiple materials contains multiple
structures with different activity. I thought that it was necessary
to visualize the individuality of catalyst to understand real
catalysis.”
Although the XAFS method has been widely developed
over the past 30 years, there have been still challenges in
identifying structural differences inside an individual catalyst
particle because of the limitation of the X-ray beam size,
which was too thick to catch a single catalyst particle. There
are large distributions of catalyst particles and the location ofactive sites and large X-ray beam cannot tell us the individual
information of the catalyst particles.
In 2008, when Dr. Tada moved to the Institute for Molecular
Science, she happened upon a state-of-the-art technique forher study. The X-ray nano-beam, which was focused X-ray

Equipment at the beamline Dr. Tada used for her experiments______ Personal drive is the criterion of research“Practical issues at industrial frontlines will also accelerate basic
research.”
While conducting advanced imaging research using the XAFS
methods, she met researchers of an automobile company. She
was overwhelmed by their desperate efforts to deal with various
issues facing in their research and development of hydrogenpowered fuel cell vehicles. As the actual operation of fuel cellvehicles progressed, new development issues rapidly appear.
However, it is not easy to look inside a fuel cell under operation.
Where are degraded parts inside a fuel cell? How do theyfind and diagnose them rapidly? To find any hint for better
understanding of the practical issues, collaborative research was
proposed to Dr. Tada.
“I decide the action of my research by personal drive.”
At the time, Dr. Tada had never been involved in research about
fuel cells, and she didn’t know basic research terms in the field.
Nevertheless, she participated in the collaborative researchwithout hesitation. Personal drive with eagerness and energy
moves researchers and a great team conducts great research.
This belief is her unwavering criterion in deciding the action ofcollaborative research, even to this day.
March 2024 | IAR LETTER | 12

Special Interview 3 | Mizuki TADA

“Even with a sophisticated research theme, there will always
be a big wall at difficult turning points. During such moments,
the strong motivation and drive of researchers break throughthe difficulties to achieve the goal. Moreover, it’s essential thateveryone involved shares the clear vision of the goal.”
In addition, when she starts collaboration with a company, sheconsiders that understanding of basic research is important. As
long as her research is conducted at a university, obtained results
are common and widely available to the public. Collaboration
with a company with understanding of basic research provides
the progress of research that cannot be done by university orcompany alone and strong relationship between academia andindustry generates that allows for mutual development.
The collaborative project finally led to large-scale national
research and development programs. Now, she enabled tovisualize reactions and degradation in fuel cells in three
dimensions using the powerful X-rays of SPring-8 andresearchers in all over the world can use this method.
These researches subsequently promoted the fusion of basic
research and industrial applications using synchrotron radiation.
As seen in the development of the next-generation synchrotron
radiation facility, NanoTerasu, scheduled to commence
operation in April 2024, research using synchrotron radiation
has now become a major platform attracting researchers fromboth academia and industries.

greatness is comparative, taking the lead among pioneers in thatfield is a daunting challenge. While emphasizing the importanceof making efforts and building a foundation supporting one’s
research within affiliated laboratory, Dr. Tada also looks outside
her own field. She often recognizes surprisingly that what iscommon in her field is unknown elsewhere. She thinks that it
is important to learn what people in other fields would like toknow and what values they hold.
Dr. Tada has an anecdote from her student days, when she actively
explored various adjacent fields outside her chemistry area.
“My supervisor at the time often told me that when we getolder, we will tend to avoid embarrassment more so that when
you are young, you should explore and present your research indifferent fields anyway.”
In her fourth year of university, her first academic conference
was one organized by the Chemical Society of Japan, but
she joined that of the organic chemistry session not of thecatalytic chemistry session. “I was fearless,” she says. She later
attended meetings and conferences when and wherever she
was called by, such as those of the Physical Society of Japan,
engineering science societies, and national or international
companies. She was surprised by difference in atmosphere,with everyone wearing suits at conferences of the Chemical
Society of Japan and otherwise with no one wearing formal
at those of the Physical Society of Japan. Positions vary
between basic and applied, and between disciplines. Eventhe choice of words to describe the same research in different
fields is completely different.
“I met various researchers. Chemists have their own way of
thinking, as do physicists, and engineers. Knowing different
values will help understanding my own field strengths andweaknesses.”

Next-generation synchrotron radiation facility, NanoTerasu, located at the Tohoku
University Aobayama New Campus in Aoba-ku, Sendai City, Miyagi Prefecture.
The energy and properties of X-rays are different from SPring-8.

______ “What is the request from society?” The importanceof meeting people and understanding their perspectives
Dr. Tada has been engaged in fusion research with researchers
in different fields of expertise and collaborative researchwith various companies even now. It is impressive that she
participates in extensive collaborations across diverse fields while
maintaining a solid foundation in her original field of expertise.
“People who constantly keep their ear to the ground of outside
fields can stay stron g. Those who merely wait until the time
is right within their own fields are difficult to acquire a new
approach.”
Of course, there is a path of refining one’s knowledge andskills to master in the same field for 40 or 50 years. However,
13 | IAR LETTER | March 2024

Different individuals from various backgrounds constructcommunity, and create new values. The crux lies in how muchone can understand what society currently needs.
“Always keeping antennas tuned to the outside world,
maintaining a solid foundation in one’s research field ofexpertise while cultivating interest in diverse subjects, and not
being afraid to ask questions of others and learn from them—these three elements are crucial. Surprisingly, there seem tobe few people who are willing to ask others to teach themsomething they don’t know.”

人と出会い、社会が求めていることを知り、新しい化学反応を起こす
唯 美津木

名古屋大学 物質科学国際研究センター／
大学院理学研究科 無機化学研究室 教授

無機材料の触媒を中心に、その合成と反応開拓、および触媒構造と反応の可視化など幅広い研究を行う。
自動車の燃料電池やタイヤゴム開発などの産業分野との共同研究も多数手がけている。

研究は人で決まる～壁を突破する情熱はあるか「触媒は実際に「使える」
ことが重要で、反応機構や原理はよくわかっていないものもたくさんあるのが現状だ。
そうした触媒の構造を捉える計測技術の一つにXAFS（ザフス；X線吸収微細構造）法がある。
エネルギーを変えながらX線を試料にあて、その吸収を測定することで、特定の元素の量や結合の状態を分析できる。2008年ごろには大型放射光施設SPring-8（スプリングエイ
ト）を活用する機会に恵まれ、さらに精密な新しい分析方法の開発にも成功した。極細のX線ビームを応用し微細な粒一つひとつにあて、世界で初めて、触媒一粒の活性種の結合を明らかにすることができた。

次世代放射光施設ナノテラス。SPring-8と比較すると、X線のエネルギ
ーや性質が違い、SPring-8は硬X線、ナノテラスは軟X線を得意とする。
宮城県仙台市青葉区の東北大学青葉山新キャンパスに整備されている「社会が知りたいことは何か？」人と出会い、相手の立場に立つ大切さ
自身の分野では当たり前であることが他の分野では案外知られていない、ということも多い。他の分野の人は何を知りたいのか。
どんな価値観を持っているのか。
「まずは所属した研究室でスキルを積み重ね、自分の研究の軸となる基盤を作ることが大切」としつつも、少し外の分野も顔を出してみるのだそうだ。
そんな唯
さんには、
化学から飛び出て近隣分野に切り込んでいった学生のころのエピソードがある。

大型放射光施設SPring-8。兵庫県佐用郡佐用町の播磨科学公園
都市に設置されている(提供:国立研究開発法人理化学研究所)

大学4年生のころ、初めて出た学会は日本化学会。
ただし、触媒化学のセッションではなく、有機化学のセッションだった。
「怖いもの知らずでした」と、その後も物理学会から工学系の学会、

XAFS法を使った先端研究を進める中で、自動車会社の研究者と出会った。研究開発で壁にぶつかっている様々な課題を何とかしたいと向き合うその必死な姿に圧倒された。水素を燃料とした燃料電池車の開発。動作中の電池の中のどこがどのように悪いのか、その場で診断する方法がなかった。
当時、唯さんは燃料
電池を触ったこともなく、基礎的な研究用語もわからなかった。
新しいことをやろうとする熱意に動かされ、躊躇することなく、共同研究を開始した。
研究はやがて、国の大型研究開発プログラムへと発展した。
SPring-8の強力なX線を使い、電池内で起こる反応や劣化の様子を、電池が「動いている」
その場で三次元的に可視化できるようになり、国内外の研究者がこの方法を使うようになった。
この研究成果はその後、放射光を利用した基礎研究と産業応用を後押しすることとなる。2024年4月に運用が開始される次世代放射光施設ナノテラスの整備に見られるように、今やX線をはじめとした放射光を利用する研究は、様々な業界の研究者が集まる大舞台となっている。

国内外の企業など声がかかるたびにどこへでも赴いた。
日本化学
会はスーツで行くが、物理学会では誰も正装していないなど、その雰囲気の違いにも驚いたそうだ。基礎と応用の違い、分野の違いなど、立場は様々。同じ研究でも、それを表現する言葉の選び方すら全く異なる。
「いろんな先生と知り合いました。化学の人には化学の人の考え方がある。物理には物理、工学には工学。様々な価値観を知る
ことで、自分の専門の強さと弱さがわかります」
立場が違う人たちが社会をつくり、そして新たな価値を生む。
いま社会が求めていることを、どれくらい知ることができるのかが勝負どころだ。
「常にアンテナを外の世界に張ること。専門の軸足はきちんと持ちつつ何でも興味をもつこと。知らないことを人に聞き、教えてもらうのを恐れないこと。
この三つが大切です。案外、知らないことを『教えてください』と言える人は少ない気がしますね」

March 2024 | IAR LETTER | 14

I.A.R. INFORMATIONI
INFORMATION

Activities & News

Nagoya University’s Institute for Advanced Research (IAR) was able to organize several on-site
events this year, including international conference.

The 10th IAR Symposium

The 6th Institute for Advanced
Webinar × MEBINAR

The IAR symposium aims to communicate
Nagoya University’s established, novel, and cuttingedge research to the wider university community andbeyond. This 10th symposium focused on the rapidly
evolving potential of AI in recent years, particularly
exploring the theme of whether AI brings about new
discoveries in academia, and discussions took place
among researchers in various fields related to AI.
Dr. Takeda from the Graduate School of Informatics
spoke about generative AI and its impact; Dr. Tsugida

A special edition of Nagoya University Online
Seminar “MEBINAR” and IAR Webinar “The truth
revealed by Egyptian archaeology and cosmic ray
imaging” was held on March 20, 2023.
Dr. Yukinori Kawae and Dr. Kunihiro Morishima,
two researchers from different fields, were invited,
and the discussion was streamed through online. Dr.
Kawae specializes in Egyptian archaeology and is trying
to clarify the structure of the three great pyramids ofGiza using precise three-dimensional measurements,
and Dr. Morishima specializes in cosmic ray imaging
and is developing technology that allows him to see
through the interior of huge structures like an X-ray
by observing muons, which is a type of cosmic ray.
After the introduction of their research, they discussed
various topics, such as an explanation of the news
announced on March 2, 2023, which identified an
unknown space in the world’s largest Pyramid of Khufu.

renowned Egyptologist. The ceremony took place at
Sakata-Hirata Hall. The day began with a courtesy visit
to University President Dr. Naoshi Sugiyama, followedby the award ceremony, moderated by Tatsuro
Ayatsuka, a science communicator. Dr. Yoshiyuki
Suto, Dean of the School of Humanities, delivered
the opening remarks, and then President Sugiyama
delivered his insightful speech, which highlighted
the University’s interdisciplinary ethos, particularlyin Egyptology. Vice President Dr. Kenji Kadomatsu
extended his congratulations. This was succeededby Dr. Hawass’s eagerly anticipated lecture thatwas fully attended, reflecting the high interest andrespect for Dr. Hawass’s work. The lecture delved
into recent archaeological findings in the Giza area.
Associate Professors Dr. Kunihiro Morishima and Dr.
Yukinori Kawae further enriched the program with
their presentations, underscoring the collaborativeand interdisciplinary nature of their research on the
Great Pyramid at Giza. Dr. Kunio Awaga, Director of
the IAR, delivered the closing remarks, and this wasfollowed by a luncheon organized by NTP Seventh Co,
LTD. The ceremony and lecture showcased Nagoya
University’s commitment to blending scientificresearch with the humanities, and the full attendance
at Dr. Hawass’s lecture spoke volumes about theacademic community’s enthusiasm for Egyptology andinterdisciplinary studies.

October 11, 2023

from the Graduate School of Informatics discussed
the large language model from the perspective of
linguistic philosophy; Dr. Ito from the Graduate
School of Informatics and Engineering at the
University of Electro-Communications addressed
Shogi, Go, and AI; Dr. Sugishita from the Graduate
School of Science at Kyoto University delved into
the intersection of physics and AI; and Dr. Katsuno
from the School of Medicine presented on the use of
AI in medicine. In addition, with Dr. Tanimura fromthe Graduate School of Informatics serving as themoderator, panel discussions on the themes of AI
and language/culture and AI and science/humanity
were conducted featuring speakers.

University-Based Institutes for
Advanced Study (UBIAS) Directors
MeetingUniversity
The UBIAS Directors Meeting, hosted by IAR,
took place from October 30 to November 1, 2023,
bringing together esteemed directors of Institutes
for Advanced Study and scholars from around theworld. The event commenced at the Center for Asian
Legal Exchange Plaza with a reception and opening
session, including welcome addresses by Nagoya
University representatives and the UBIAS Coordination
team: Prof. Olivier Bouin from the French Networkof Institutes for Advanced Study (Paris, France),
Profs. Grace Diabah and Susann Baller of the Merian
Institute for Advanced Study in Africa (Accra, Ghana),
and Prof. Kunio Awaga, Director of Nagoya IAR. The
first day focused on the evolution and reach of UBIAS,
featuring a panel discussion about its foundation,

Celebrating Interdisciplinary Excellence:
Dr. Zahi Hawass Receives Honorary
Doctorate at Nagoya University
On September 29, 2023, Nagoya University’s
School of Humanities and IAR hosted an event toconfer an honorary doctorate on Dr. Zahi Hawass, a

15 | IAR LETTER | March 2024

March 2024 | IAR LETTER | 16

INFORMATION

Activities & News

I.A.R. INFORMATION

2023 Young Leaders Cultivation (YLC)
Program
The YLC program is a strategic program of Nagoya
IAR based on the premise that it is crucial to secure an
appropriate quantity and quality of young researchers
to sustain the development of outstanding education
and research in the future. The Nagoya IAR recruits andtrains young faculty members regularly andsystematically. In the academic year 2023, Dr. Keiko
Kawano (Graduate School of Humanities), Dr. Satoshi
Ikegaya (Graduate School of Engineering), Dr. Jia Wang
(Institute of Materials and Systems for Sustainability),
D r. At s u s h i U s a m i ( I n s t i t u te o f Tra n s fo r m a t i v e
Bio-Molecules), Dr. Shohei Saga (Kobayashi-Maskawa
development, future, and global impact. Key topics
included promoting interdisciplinary scholarship,
fostering global diversity in scientific exchanges, andsupporting young scholars. The evening concluded
with a dinner gathering. The second day’s sessions
were held at the historic Yagoto-san Koushoji temple,
commencing with a traditional Japanese tea
c e r e m o n y. T h i s d ay ’s a g e n d a r e v o l v e d a r o u n dthematic sessions, starting with “Sensing Invisibles
and Society Change.” The session highlighted Nagoya

phenomena like environmental contamination andpandemic impacts. This was followed by a session on“Digital Humanities” and “Artificial Intelligence,”
ex p l o r i n g t h e i nt e r s e c t i o n o f t e c h n o l o g y w i t hhumanities and the transformative impact of AI
across various sectors. The afternoon saw discussions
on “Energy/Environmental Transitions,” addressing
critical global challenges such as climate change andsustainable energy solutions. The final day, located at
the Center for Asian Legal E xchange Plaza, wasprospects for ICA 5, the Topic of the Year 2024, andnew collaborative initiatives. The meeting concluded
with an excursion to Nago ya Castle, providing amoment of relaxation and reflection. Throughout theevent, thematic sessions included Nagoya University
fa c u l t y ’s o p e n i n g s p e e c h e s , fo l l o w e d b y U B I A S
members’ presentations and panel discussions.
Overall, the UBIAS Di rectors Meeting was a
testament to the power of interdisciplinary researchand global collaboration in academia, addressing

University’s expertise in visualization technologies
and their applications in understanding complex

dedicated to the UBIAS Business Meeting. Key topics
included membership, decentralized operations,contemporary challenges and fostering innovation fora better future.

Institute), Dr. Yuki Sugiyama (Graduate School of
Science), Dr. Shohei Iyoshi and Dr. Koyo Tsujikawa(Graduate School of Medicine), and Dr. Fanny Bellegarde(Graduate School of Bioagricultural Sciences) were
newly employed as designated assistant professors of
the YLC program.

YLC Seminar
The YLC seminar aimed to provide members with
opportunities in order to understand each other ’s
re s e a rch inte re st s t o a s s i st i n i nterd i s c i p l i n a r ycollaboration research. The 30th YLC seminar wasorganized in Hybrid on March 3, 2023. Dr. Su Matthew
Paul (Graduate School of Science) talked about “Exploring
the mechanisms linking the circadian clock, hearing andcopulation in mosquitoes,” and Dr. Hideki Umehata(Graduate School of Science) talked about “Cosmic web
filaments and galaxy evolution.” The 31st YLC seminar
was organized in Hybrid on June 9, 2023. Dr. Minoru
Hirose (Graduate School of Mathematics) talked about“Exploring the world of multiple zeta values,” and Dr.
Sanae Ito (Graduate School of Humanities) talked about“State communications in the Assyrian Empire.” The 32nd
YLC seminar was organized in Hybrid on December 1,
2023. Dr. Elena Kozgunova (Graduate School of Science)talked about “Cells within a cell: novel chloroplast

17 | IAR LETTER | March 2024

March 2024 | IAR LETTER | 18

INFORMATION

Activities & Newsdivision gene discovered through genetic screening,” andDr. Satoshi Ikegaya (Graduate School of Engineering)talked about “ Topological condensed matters andbeyond: Multi-locational Majorana zero modes.”I.A.R. INFORMATION“Invitation to the Advanced
Researches” IAR Lecture SeriesThis lecture series includes lectures by the IAR
academy and faculty members, IAR fellows, and Nagoya
University researchers and targets Nagoya University
students. This series aimed to communicate the fun ofacademic research. In the academic year 2023, there
were 15 lectures that occurred online:
1.“Science Started from Observation,”
Prof. Sumio Iijima（Guest Professor at Nagoya University and Professor at Meijo University）

12.“Unraveling life systems using chemical and genetic approaches,”
Prof. Shigeki Kiyonaka（Graduate School of Engineering）

13.“Signaling Molecules Make Plant Life Resilient,”
Prof. Hitoshi Sakakibara

Dr. Kazuo Shonozaki

14.“Next-Generation Bio-imaging,”
Prof. Shigehiro Yamaguchi( R i ken/ Nagoya U n i v e rs i t y ) re c e i v e d t h e J a p a n
Academy Prize (June 2023), The Order of the Sacred
Treasure, Gold and Silver Star (November 2023),
Highly Cited Researchers 2023, Clarivate (November
2 0 2 3 ) , a n d B e s t S c i e n t i s t s i n t h e Wo r l d 2 0 2 3 ,Research.com (December 2023).

（Deputy Director of IAR and Graduate School of Bioagricultural Sciences）（Graduate School of Science and Institute of Transformative Bio-Molecules）

15.“Concluding the Course of Invitation to the Advanced Researches,”
Prof. Yoshiyuki Suto
（Eighth Director of IAR）

（President of Nagoya University）

3.“What are building blocks of the universe?,”Prof. Yoshitaka Itow
（Institute for Space-Environmental Research）

Dr. Minoru Hirose

4.“Material Science—Fun and Useful,”Prof. Ichiro Terasaki(IAR/Graduate School of Mathematics) received
Frontiers of Science Award/International Congress of
Basic Science (January 2023).

（Graduate School of Science）

Dr. Hisashi Hayakawa

5.“The Present in Historical Studies: Excavate the Hellenism Civilization,”
Prof. Yoshiyuki Suto
（Graduate School of Humanities and Eighth Director of IAR）

6.“Analyzing society and economy through the eyes of game theory,”
Prof. Akihiko Yanase（Graduate School of Economics）

7.“Exploring underground structure with seismic wave,”Prof. Koushun Yamaoka（Graduate School of Environment）

T h e Y L C c o l l a b o r a t i v e r e s e a r c h g ra n t w a s
launched in 2018 to support the interdisciplinary collaboration between YLC faculties. YLC faculty voluntarily organized the grant contents, schedule, and selection process. In this year, YLC selected two researchgroups: one group was led by Dr. Sanae Ito (Graduate
School of Humanities) with the title “Analyzing andContextualizing Solar Eclipses in the Ancient East” andthe other by Dr. Yuichiro Tada (Graduate School of Science) with the title “Physics meets Mathematics.”

19 | IAR LETTER | March 2024

Dr. Hitoshi Sakakibara(IAR/Graduate School of Bioagricultural Sciences)received Ishii Kenichiro Award (December 2023),
Medal with Purple Ribbon (November 2023), Highly
Cited Researcher (November 2023), and JSPP Award(March 2023).

2.“The Dark Side of the Universe,”
Prof. Naoshi Sugiyama

YLC Collaborative Research Grant

Awards

8.“Analyze Democracy,”Prof. Hiroko Takeda（Graduate School of Law and Deputy Director of Nagoya IAR）

9.“Fascination with an Introduction to the History of Thought,”
Prof. Takaho Ando
（Chukyo University and Sixth Director of Nagoya IAR）

10.“Physical chemistry of energy and the environment,”
Prof. Kunio Awaga（Director of IAR and Graduate School of Science）

11.“Mechanisms underlying the mysterious existence life,”
Prof. Kazuhiro Nakamura（Graduate School of Medicine）

Short-Term Fellowship Program
To facilitate international scientific cooperation, thisprogram supports short research visits of overseas researchers(maximum of 4 weeks), including related activities such as
holding a symposium. In the academic year 2023, Dr. Alstair
Phillips (Professor at Warwick University), Dr. Sakiko Okumoto(Associate Professor at Texas A&M University), and Dr. Yavuz
Duvarici (Professor at Izmir Institute of Technology) wereselected for this fellowship.

Foreign Principal Investigator
Fellowship Program
The Foreign Principal Investigator Fellowship Program invites
excellent researchers from foreign countries with outstanding
research achievements for 3–4 months of
fellowship to promote the Universities’ academic
research. In the academic year 2023, Dr. Guy Le
L ay ( E m e r i t u s P ro fe s s o r a t A i x M a rs e i l l e
University) was selected for this fellowship.

( I A R / I n st i t u te fo r A p a c e - Ea r t h E nv i ro n m e nta lResearch) received Young Scientists’ Award from The
Commendation for Science and Technology by the
Minister of Education, Culture, Sports, Science andTechnology (April 2023).

Dr. Koyo Tsujikawa(IAR/Graduate School of Medicine) received Medical
Research Award 2022 (February 2023).

Dr. Hideki Umehata(IAR/Graduate School of Science) received MEXT The
Young Scientists’ Award (April 2023).

Dr. Atsushi Usami(IAR/Institute of Transformative Bio-Molecules)
received Award for Excellence/The Public Foundationof Chubu Science and Technology Center (December2023) and Konica Minolta Research PlanningAward/The Society of Synthetic Organic Chemistry,
Japan (December 2023).

March 2024 | IAR LETTER | 20

Research Highlights _ 01

Uncover the function of epigenetic regulation inplants nitrate nutrition stresses and its memory

Topology in Superconducting Proximity Effects

Fanny BELLEGARDE

Satoshi IKEGAYA

Designated Assistant Professor of Young Leaders Cultivation Program

Designated Assistant Professor of Young Leaders Cultivation Program

Graduate School of Bioagricultural Sciences/ Institute for Advanced Research, Nagoya University

Graduate School of Engineering / Institute for Advanced Research, Nagoya University

E-mail: fannyb@nuagr1.agr.nagoya-u.ac.jp

E-mail: ikegaya@rover.nuap.nagoya-u.ac.jp

INTRODUCTION

In natural environments, nitrate concentration of the soil
fluctuates greatly and often limits plant growth and development.
Therefore, the ability of plants to respond to changes in nitrateavailability is essential for adaptation. Plants integrate local sensing
and long-distance signaling to adapt their growth depending on
nutrient availability.
Transcriptional regulation of gene expression is one of themost important processes plants use to adapt the properties of theroot system in response to local and long-distance signaling [1]. The
access to DNA information is controlled by the chromatin (associationof DNA with histone protein), which different modifications,called epigenetic marks, target. These marks organize the genetic
information by modulating
the accessibility to DNA (Fig.
1). Epigenetic regulation isvital during plant development
and in plant adaptation tostresses. Most epigenetic
studies have been focusing onplant development. However,
only a few studies investigatede p i g e n e t i c s ’ f u n c t i o n i n Figure 1. Epigenetic marks regulate accessnutritional stresses.
to DNAEPIGENETIC FUNCTION IN LIMITED AND EXCESSIVENITRATE NUTRITION STRESSES

To address this gap, I studied whether epigenetics regulates
DNA expression of the main root nitrate transporter NRT2.1. Thistransporter is involved in absorbing nitrate from the soil to the root,
especially when nitrate is limited. We showed that a strong repressive
epigenetic mark (H3K27me3) deposited by the methyl-transferase CLF
directly regulates the NRT2.1 gene, in a context where it is strongly
expressed, to temper its expression [2]. This regulation reveals a novel
non-canonical role for this mark as a safeguard for expressing highly
expressed genes (genome-wide). We recently revealed that suppressing
this limitation leads to massive RNA degradation and finally completely
stops gene expression [3]. This work reveals the importance of finetuning expression by epigenetics for plant physiology, although it is
not involved directly in nutritional regulation.
Then, we investigated the function of epigenetics in excessive
nitrate stress response. We highlighted that excessive nitrate
uptake leads to oxidative stress. Strong deleterious effects emerge
if epigenetic regulations, the activation of detoxifying proteinscounteracting oxidative stress, do not occur [4].
Our results show that epigenetic regulations protect plants fromlimited and excessive nitrate stresses.

EPIGENETIC FUNCTION IN PLANT ADAPTATION TO A
FLUCTUATING NITRATE ENVIRONMENT

21 | IAR LETTER | March 2024

Research Highlights _ 02

While researching epigenetic function in nitrate nutrition, I
developed a research project studying epigenetic involvement inregulating an important plant growth hormone for long-distancenitrate signaling, the cytokinin (CK).
To this end, I performed a time-course experiment during nitratefluctuation (nitrate-starvationnitrate resupply). My results
revealed that nitrate fluctuation
modifies epigenetic profiles at
IPT3 gene, a key CK biosynthesis
gene. Mis-regulations of
epigenetic settings strongly
impact IPT3 regulation by nitratefluctuation and CK content,
revealing that the epigenetic
modification constitutes aregulatory mechanism of IPT3 F i g u r e 2 . E p i g e n e t i c d y n a m i c a l l ydepending on nitrate availability regulates hormonal synthesis depending(Fig. 2) [5].
on nitrate availability

CURRENT FOCUS

Accumulating evidence reveals that epigenetic regulation can also
constitute a stress-induced environmental memory. Recently, I foundthat the first controlled starvation stress event can prime the plant
to resist a second longer stress. Therefore, my current project aims to
elucidate mechanisms by which plants can remember a past nitrate
starvation stress event to tolerate a future, longer stress by studying
the molecular, hormonal, and physiological changes during repeatednitrate fluctuation stress. My research focuses on the model plant
Arabidopsis, as a tool of explorative research, to understand how
this memory is set and connect epigenetic regulation with tolerance
to nitrate fluctuation stress. Then, this knowledge will be employed
to guide the research on crop species and develop a technology for
producing tolerant-to-nitrate-fluctuation-stress seedlings.

REFERENCES[1] Bellegarde F., Gojon A., Martin A., (2017) Signals and players in thetranscriptional regulation of root responses by local and systemic N signalingin Arabidopsis thaliana. J. Exp. Bot. 68(10): 2553-2565.
[2] Bellegarde F., Herbert L., Séré D., et al., (2018). Polycomb Repressive
Complex 2 attenuates the very high expression of the Arabidopsis gene
NRT2.1. Sci. Rep. 8(1): 7905.
[3] Séré D., Cassan O., Bellegarde F., et al., (2022) Loss of Polycomb proteins
CLF and LHP1 leads to excessive RNA degradation in Arabidopsis. J. Exp. Bot.
73(16) :5400-5413.
[4] Bellegarde F., Maghiaoui A., Boucherez J., et al., (2019). The chromatin
factor HNI9 and ELONGATED HYPOCOTYL 5 maintain ROS homeostasis underhigh nitrogen provision. Plant Physiol. 180(1): 582-592.
[5] Bellegarde F., Tjahjono O., Shibutani M., et al. Fluctuation in nitrateavailability impacts histone modifications of the cytokinin biosynthesis gene
IPT3 in Arabidopsis roots (in preparation)

INTRODUCTION

When a metal is attached to a superconductor, Cooper pairs
which are quasi-particles responsible for the superconductivity
penetrate the attached metal from the superconductor andsubsequently modify the electromagnetic properties. Thisphenomenon is referred to as the superconducting proximity
effect [1] and has been a central research topic in the physics
of superconductivity since the 1950s. From the beginning of
the 2000s, the proximity effects of anisotropic superconductors,
such as high-Tc cuprate superconductors, have been studied
intensively. In 2004, the proximity effects from spin-triplet
nodal superconductors, a kind of anisotropic superconductors,
were extremely unconventional. Specifically, in a junction of aspin-triplet nodal superconductor and a disordered metal, thedifferential charge conductance G at zero-bias voltage quantizes
robustly at a very high value containing only universal constants
and an integer number as

ven though the conductance of the disordered metal by itself is
extremely low [2]. Here, e denotes the elementary charge, h is
the Planck constant, and Z represents an integer number. Suchdramatic proximity effect of spin-triplet nodal superconductors has
been referred to as an anomalous proximity effect. In the 2010s,
it was widely recognized that the anomalous proximity effect isrelated to exotic quasi-particles, such as Majorana particles [3]and odd-frequency Cooper pairs [4]. Therefore, the anomalous
proximity effect became interesting in this research field.
Nevertheless, a fundamental question, “why does the conductancequantize?”, has remained unresolved for over ten years.

INDEX THEOREM

The quantization of physical quantities is sometimes related
to mathematical invariants. For instance, when a strong magnetic
field is applied to a two-dimensional electron gas, the Hall
conductivity is quantized to a value characterized by a topologicalinvariant called the Chern number [5]. The robustness of thequantization against impurities can be explained by the fact thatthe topological invariant is independent of the strength of thedisordered potentials. Here, we have come to suppose that the
conductance quantization of the anomalous proximity effect may
be understood by employing some kind of topological invariants.
At first, by using quasi-classical Green’s function techniques,
we have obtained the analytical expression for the integer number
characterizing the anomalous proximity effect:

where k_∥ represents a wave number parallel to the junction
interface we consider. More importantly, we find that w(k_∥)
is a one-dimensional winding number, a topological invariant
characterizing the topological properties of the superconductor in
the clean limit. Here, we see that the anomalous proximity effect is

indeed related to the topology [6,7].
The Atiyah-Singer index theorem mathematically relates a
topological invariant with an invariant defined in terms of solutionsof a differential equation. By combining this mathematicaltheorem with the Bogoliubov-de Gennes equation, a fundamental
equation describing superconducting systems, we have proved thatthe topological invariant Z is exactly consistent with the number ofthe resonant states at zero energy, N_Res, which contributes to thecharge conductance quantization [8,9]:
Z=N_Res.

CONCLUSION

We have microscopically understood the anomalous proximity
effect by employing the Atiyah-Singer index theorem. Eventually,
it turns out that the anomalous proximity effect is a novel type of
topological quantization phenomena, an important research topic
in condensed matter physics today.

REFERENCES[1] A. F. Andreev, Sov. Phys. JETP 19, 1228 (1964).
[2] Y. Tanaka and S. Kahiwaya, Phys. Rev. B 70, 012507 (2004).
[3] N. Read and D. Green, Phys. Rev. B 61, 10267 (2000).
[4] Y. Tanaka and A. A. Golubov, Phys. Rev. Lett. 98, 037003 (2007).
[5] D. J. Thouless, et. al., Phys. Rev. Lett. 49, 405 (1982).
[6] S. Ikegaya, Y. Asano, and Y. Tanaka, Phy. Rev. B 91, 174511 (2015).
[7] S. Ikegaya, et. al., Phy. Rev. B 94, 054512 (2016).

March 2024 | IAR LETTER | 22

Research Highlights _ 03

Let the fat out of the bag: Revealing the role ofadipose tissues as minions of ovarian cancer

Art in modernity and Diderot's philosophy

Shohei IYOSHI

Keiko KAWANO

Designated Assistant Professor of Young Leaders Cultivation Program

Designated Assistant Professor of Young Leaders Cultivation Program

Graduate School of Medicine / Institute for Advanced Research, Nagoya University

Graduate School of Humanities / Institute for Advanced Research, Nagoya University

E-mail: iyoshi.shohei@med.nagoya-u.ac.jp

E-mail: kawano.keiko.n8@f.mail.nagoya-u.ac.jp

INTRODUCTION
Ovarian cancer (OvCa) is one of the most prognosticallyunfavorable tumors in gynecologic oncology. Due to the lack ofnoticeable symptoms and the absence of an established screening
method, many cases are found in advanced stages with multiple
metastatic nodules in the abdominal cavity, called peritoneal
dissemination. In the formation of peritoneal dissemination, OvCa
cells are known to exhibit a tropism to the tissues rich in adipocytes,
including the greater omentum and mesentery. Removing all
metastatic lesions completely during the initial surgery is difficult,and most cases experience recurrence. Therefore, understanding
and controlling the pathophysiology of peritoneal dissemination
are crucial in overcoming OvCa. Concerning the mechanism of how
adipose tissues play roles in the peritoneal dissemination of OvCa,
there are still a lot of unclear points. In this context, the crosstalk
between adipose tissue and OvCa was investigated from basic andclinical research approaches.

DEDIFFERENTIATION OF ADIPOCYTE
When adipocytes obtained from surgically resected omentum
were co-cultured with OvCa cells, it was observed that lipiddroplets were fallen out from adipocyte and the fibroblastlike cells appeared 1. The obtained cells were named omental
adipocyte-derived fibroblasts (O-ADF), and the characterization of
O-ADF by flow cytometry analysis revealed that OADF possesses
mesenchymal stem cell and myofibroblast-like features. Wnt/
β-catenin pathway was identified as a key signaling pathway
involved in this dedifferentiation process. Then, the effects of
O-ADF on OvCa cells were examined, and co-culturing with O-ADF
was confirmed to promote the growth and enhance the migration
ability of OvCa cells. Supplementation of TGF-β1, known to exit inhigher concentration in malignant OvCa ascites, showed further
activation of O-ADF and increased these protumoral abilities. Upon
pathway enrichment analysis with proteomic dataset of the OvCa
cells co-cultured with O-ADF, pro-tumoral cellular pathways, suchas glycolysis/gluconeogenesis, pentose phosphate pathway, andDNA replication, were confirmed to be enriched. These tumorsupportive roles of O-ADF were also confirmed in vivo using OvCadisseminated mouse models. From this basic research approach,
O-ADF induced by OvCa cells contributed to the neoplastic growthof OvCa at adipocyte-rich tissues in the abdominal cavity (Figure 1).

OBESITY AND THE STEALTH MICRO-METASTASISThe effect of adipose tissue upon the sprout of OvCa fromstealth micro-metastasis was analyzed using a multicenterr e t r o s p e c t i v e c l i n i c a l s t u d y 2. T h e s t u d y u s e d d a t a f r o mapproximately 5,000 patients with malignant ovarian tumors
collected over 35 years in the Tokai Ovarian Tumor Study Group.
Patients with stage IIB to IIIC (meaning that they experienced

23 | IAR LETTER | March 2024

Research Highlights _ 04

INTRODUCTION

Diderot is the leading philosopher of the 18th-century French
Enlightenment and is known for editing the Encyclopaedia. His thought
spanned a wide range of fields, from socio-political theory to naturalscience, language theory, and art theory. France in the 18th century
was a period when eminent philosophers, such as Rousseau andMontesquieu, were active, and their thoughts were also transcendental.
However, Diderot's interest in art is more exceptional than thosephilosophers. Why did Diderot attach so much importance to art theory?
This is the fundamental question I am currently tackling in my research.

WEIGHTLESSNESS IN WORKS OF ART

Figure 1. Induction of omental adipocyte dedifferentiation by OvCa cell, andthe effect of generated O-ADF on OvCa cells in the tumor microenvironment atomental dissemination

peritoneal metastasis) epithelial OvCa who had achieved complete
resection of the visible lesion were included. A total of 280
patients who satisfied the study criteria were included in the
study and classified into 3 groups based on their body mass index(BMI) at diagnosis. In addition to overall survival and progressionfree survival, peritoneum-specific recurrence-free survival was
evaluated. The results showed that peritoneum-specific recurrencefree survival and overall survival were significantly shorter in thehigh BMI group than in the normal BMI group (p = 0.028 and0.018, respectively). Multivariate analysis identified obesity as anindependent prognostic factor. This clinical research approachrevealed that, upon recurrence from hiding OvCa cells, adipose
tissue plays pro-tumoral roles and supports their sprout frommicro-metastatic sites.

CONCLUSION
From obtained results, it is speculated that OvCa cells utilize
the adipose tissue in the abdominal cavity as a way-stop point.
They hide and acquire supporters there to create a foothold forfurther metastasis. Peritoneal dissemination is also frequently
observed in other cancer types, including gastric colorectal cancer,
indicating that novel therapies targeting adipose tissue may apply
to various cancers. The development of such treatment is strongly
desired, and I would like to open the way.

REFERENCES[1] Iyoshi, S. et al. Pro-tumoral behavior of omental adipocyte-derived
fibroblasts in tumor microenvironment at the metastatic site of ovariancancer. Int. J. Cancer 149, 1961–1972 (2021)[2] Iyoshi, S. et al. Obesity contributes to the stealth peritoneal disseminationof ovarian cancer: a multi-institutional retrospective cohort study. Obesity 30,
1599–1607 (2022)

In Western thought, the existence of God was absolute. Everything,
the world works, the origin of man, the origin of language, etc., were
all explained by God. In the 18th century Enlightenment, however, after
Locke’s empiricism, man was finally freed from the superstition of God
and began to search for the truth of the world on his own and throughhis own senses. Therefore, the philosophers of this period must define
all things in the world, social systems, nature, language, etc., without
the existence of God. This is why the scope of their thought naturally
expanded. Diderot was no exception, and at the root of his thought
was a strong self-consciousness as a modern man freed from God.
Nevertheless, art theories in this period were often written by paintersor theorists of literature rather than philosophers. So, why did Diderot
make art theories part of his philosophical field of thought? In the fieldof art, Diderot is famous as a pioneer of art criticism. Diderot repeatedlyrefers to the issue of the representation of the weight of objects andgravity in works of art when he is involved in the art criticism of theexhibition called Salon, organized by the Royal Academy of Fine Arts.
For example, he notes that the “flying figures” in the upper right-handcorner of the painting Ulysses Invoking the Spirit of Tiresias (Figure 1)
are floating, despite having bodies similar to ours, yet these figures do
not shock but delight the modern viewer (1).
The background to Diderot's point is still the problem of modernity.
In particular, the development of natural science in the modern era.
When God existed, the view of nature accepted weightlessness, suchas the flight of God or the flying and leaping of angels. However, theperception of modern man, who now lives in an age in which God has
been lost, is essentially governed by the law of gravity and should only
accept the weight of objects and the existence of objects to the extent
that they conform to the laws of nature. For example, Blake painted
Newton assimilating with a rock and moving a compass on the ground(Figure 2). Yet Diderot, a modern man, is delighted, rather than shocked,
to see flying figures in the paintings. How is such a thing possible? Whatis art for modern people? This is one of the central questions of Diderot's
theory of art. Therefore, it seems that for Diderot, art theory was animportant field to interrogate the mysterious human cognitive capacity
or imagination, which, even in modern times dominated by naturalscience, is still freely invoked without regard to natural laws.

ART AND RELIGION IN MODERN

Should we consider the question of imagination in Diderot's
philosophy? I will relate this question to religion in modernity. In
modernity, God has been lost, and natural science has become the newparadigm. Nevertheless, only the human imagination is not bound by
the laws of nature and still imagines an absent entity. This paradox isa major problem for Diderot's theory of art, which he attributes to his

Figure l. Bouchardon, Ulysses Invoking the Spirit of Tiresias bouchardon,1738,
Musée du Louvre. (cut-out part) © Musée du Louvre

Figure 2. William Blake, Newton, 1795-c. 1805, Tate Britain. Photo: Tate in the 18th
century, the philosopher Newton was depicted as assimilating with the ground.

strong interest in Pascal, the giant of early modern natural philosophy
and theology. While Pascal, as is well known, made great achievements
in natural philosophy, he also expounded a belief in God, which isessentially contradictory to natural philosophy, in his chapter-based
work Pensées. In 1746, Diderot wrote Pensées philosophiques, which
imitated Pascal's chapter style of writing and ridiculed theologicalthought, and in his later years, he wrote Pensées sur l’interprétationde la peinture. This suggests that Diderot had Pascal, the giant of thenatural sciences and theology, in his mind, and that in the modern
age when God had been lost, “art” was placed alongside the naturalsciences in place of God, and he philosophically questioned themysterious cognitive abilities of human beings. Based on this hypothesis,
I will try to elucidate Diderot's theory of art from various perspectives
based on his natural science theory and religious theory.
REFERENCES[1] Denis Diderot, Sur Bouchardon et la sculpture , 1766, Œuvres complètes,Arts et lettres: 1739-1766 : critique I, t.13 , éd. Jean Varloot [et al.], Paris,
Hermann, 1979, p. 331.

March 2024 | IAR LETTER | 24

Research Highlights _ 05

Understanding the dynamics of the large-scale
structure of the Universe

Revealing autolytic mechanisms of sieve element
differentiation

Shohei SAGA

Yuki SUGIYAMA

Designated Assistant Professor of Young Leaders Cultivation Program

Designated Assistant Professor of Young Leaders Cultivation Program

Kobayashi-Maskawa Institute / Institute for Advanced Research, Nagoya University

Graduate School of Science / Institute for Advanced Research, Nagoya University

E-mail: saga@kmi.nagoya-u.ac.jp

E-mail: sugiyama.yuki.d8@f.mail.nagoya-u.ac.jp

INTRODUCTION

Recent cosmological observations have revealed that thedominant matter component of the Universe is unknown cold
dark matter (CDM), which interacts solely through gravitational
force and hence is never seen with light. The nature and originof CDM have been extensively discussed through theoretical andobservational ways. So far, in particular, observations of the cosmic
microwave background radiation have successfully extracted
cosmological information, indicating the existence of CDM anddark energy which drives accelerated expansion. Meanwhile, myfocus lies on the large-scale structure of the Universe, the largest
structure in the Universe formed by galaxies. A characteristic weblike structure is observed when we make a three-dimensional
map of galaxies, which are used as points of sources, we observea characteristic web-like structure. This large-scale structure of
the Universe is seeded by fluctuations in the early Universe during
inflation and has developed as a result of the gravitational forceof CDMs. Therefore, investigating the large-scale structure of the
Universe offers a captivating opportunity to unveil the nature ofdark matters and extract the information about the primordial
Universe. Constructing accurate theoretical models is crucial for
extracting cosmological information from observations of thelarge-scale structure of the Universe. However, the non-linearity ofgravity in CDM evolution poses a significant challenge to achieving
this.

DYNAMICS OF COLD DARK MATTERS

The cold nature of dark matter implies that the initial velocity
dispersion is negligibly small and the phase space of CDM (a sixdimensional space representing the distribution of dark matter
positions and velocities) exhibits a three-dimensional sheet
structure. Therefore, even if the sheets have a simple structure
without folds initially (referred to as single stream region, see
the left panel in Fig.1), non-linear growth due to gravity causes
self-intersections of the sheets, called shell crossing (center panelin Fig.1). As a result, they form complex structures called multistream flow (right panel in Fig.1). During the early stages, we canfollow the CDM evolution using perturbative treatment, which has
successfully predicted statistics related to the large-scale structureof the Universe and facilitated comparisons with observations.
However, the perturbative treatment breaks down at shell crossing
and in the multi-stream regions. Therefore, it is crucial for futurecosmological observations to accurately predict statistical quantitiesof the large-scale structure of the Universe by properly following
the evolution of the CDM.

IMPROVING THE ANALYTICAL PREDICTIONSTo improve the analytical prediction in the vicinity of the shellcrossing and/or in the multi-stream region, we have investigated

25 | IAR LETTER | March 2024

Research Highlights _ 06

RESEARCH BACKGROUND

Figure 1. Dynamical evolution of CDM in phase space, i.e., velocity-position space,[top panels] and its density field in real space [bottom panels]. The time evolution
is shown from the left to the right panels, with the left and right panels showing
the early and late stages, respectively. The CDM is initially set to have a small peakat the origin, and the surrounding CDMs fall towards the center due to gravity.
Blue and orange lines show the simulation results and Zel’dovich solution, a simple
prescription to describe the evolution of CDM.the evolution of CDM.

the convergence property of the perturbative approach by using
the very high-order perturbation order, specifically the 15th orderin 3D space[1, 2]. Owing to having the high-order perturbative
solutions, we have found the resummation technique for the
perturbative series and then extrapolated the perturbative order
to infinity, leading to the non-perturbative analytical predictions.
Our approach’s prediction remarkably agrees with the simulation
results in the phase-space structure. We have further investigatedthe CDM dynamics shortly after shell-crossing time. One of theprominent features in the multi-stream regime is the presence ofthe vorticity fields (rotation of velocity fields), absent in the singlestream regime. The vorticity fields serve as interesting observables
for understanding CDM dynamics. We developed a method topredict the multi-stream quantities relying on the perturbative
prediction at the shell-crossing time. This method allows us topredict the vorticity fields, which agree with the simulation
measurements. Our advancement in perturbative approaches canbe a fundamental technique for predicting CDM motion evenbeyond shell crossing and in the multi-stream regime. Then, in
future works, our results will qualitatively improve the analyticalprediction of the statistical quantities in the large-scale structureof the Universe, and extract the cosmological information to reveal
the nature of dark matters.

REFERENCES[1] Saga S, Taruya A, and Colombi S, Physical Review Letters 121, 241302 (2018)[2] Saga S, Taruya A, and Colombi S, Astronomy & Astrophysics 664, A3 (2022)

To gain special functions, cells sometimes lose something. For
instance, the animal sperm achieves high motility due to the lackof most cytoplasm and organelles. In flowering plants, the sieveelements (SEs), the individual component of the phloem sievetube, lose most of the cytoplasm and organelles, as well as partof their cell wall (Figure 1). Degradation of the cytoplasm andorganelles results in a nearly hollow structure, allowing the sievesap, containing photosynthetic products and signaling molecules,
to pass through. In parallel, spatially controlled degradation of thecell wall generates small holes, namely sieve pores, at both ends ofthe cell, enabling the SEs to connect to each other. Although thesedrastic rearrangements of cellular components have been shownas crucial steps for the sieve tube to function, the molecular basis
underlying these dramatic changes is still elusive.
The poor progress in the molecular and cell biology of SEs
is mainly due to the extreme difficulty of observing these cells.
Since SEs lack morphological features other than somewhat thickcell walls, it is hard to distinguish them from surrounding cells.
Furthermore, their deep location within the tissue is a major
obstacle to confocal live imaging. Fortunately, recent advances ingenetics and experimental techniques have dramatically improved
today's situation. Multiple genes specifically expressed in SEs havebeen identified and their promoters can now be used to visualize
SEs at various developmental stages. In addition, identifying
transcription factors such as APL and NAC45/86 allowed us to follow
the behavior of downstream molecules by transcriptome analysis (1).
Besides, developing an induction system, called VISUAL, hasmade it possible to transdifferentiate model plants Arabidopsis
thaliana leaf mesophyll cells into SE-like cells (2). The cells induced
by VISUAL undergo remodeling of cellular components, including
nuclear degradation and callose deposition, a cell wall component
abundant in SEs. These cells also express several SE marker genes,suggesting that they can be considered as SEs. While this system istruly innovative because it can easily and efficiently induce SEs, it
still is not good enough for analysis from a cell biology perspective.
The reason is that the base mesophyll cells are also small andlocated deep in the tissue and are therefore not as suitable for live
imaging as the original SEs. Another disadvantage is that the sparsepresence of mesophyll cells in the first place makes it difficult toform interconnected structures, or sieve plates, between cells.

MY PROJECT

I applied the VISUAL technique to Arabidopsis hypocotyl cells
rather than leaf mesophylls to develop a new induction system(Figure 2). I found that the combination of VISUAL and hypocotyl
can address the weaknesses of the conventional VISUAL. Comparedto the original technique using leaf mesophylls, hypocotyl cells are
more similar in their shape to SEs and are therefore more likely
to maintain the top-down cell polarity and cell division direction.
This also allows detailed imaging of the intracellular dynamics
of SE differentiation by inducing the formation of large, easily
observable SEs. Several SE markers, including APL and NAC86, areindeed expressed in induced SEs. The gradual disappearance of

Figure 1. A schematic diagram of SE differentiation.

Figure 2. Induced SEs in a hypocotyl (left). Time-course imaging of Nuclei (topright) and Golgi (bottom right) degradation.

the nuclear and Golgi signals was well observed by live imaging
in induced cells (Figure 2). Further electron micrographs showedthat structural changes characteristic of SE differentiation, suchas the occurrence of cytoplasm clearance and formation of sieve
plates, were largely reproduced in induced cells. Therefore, theinduced cells in hypocotyls have sufficient morphological evidence
to be considered SEs. Using this system, I will intricately visualizeorganelle degradation during SE differentiation and find key
factors to reveal the molecular mechanisms.

REFERENCES[1] Furuta K. M. et al., Arabidopsis NAC45/86 direct sieve element
morphogenesis culminating in enucleation. Science 345, 933-937 (2014).
[2] Kondo Y. et al., Vascular cell induction culture system using Arabidopsis
leaves (VISUAL) reveals the sequential differentiation of sieve element-likecells. Plant Cell 28, 1250-1262 (2016).

March 2024 | IAR LETTER | 26

Research Highlights _ 08

Research Highlights _ 07

Integrating genomics and biophysics
to comprehend tauopathy
Koyo TSUJIKAWA

Atsushi USAMI

Designated Assistant Professor of Young Leaders Cultivation Program

Designated Assistant Professor of Young Leaders Cultivation Program

Graduate School of Medicine / Institute for Advanced Research, Nagoya University

Institute of Transformative Bio-Molecules (ITbM) / Institute for Advanced Research, Nagoya University

E-mail: tsukoyo@med.nagoya-u.ac.jp

E-mail: usami.atsushi.y5@f.mail.nagoya-u.ac.jp

INTRODUCTION

Mammalian cell cytoskeleton comprises microtubules, actin
filaments, and intermediate filaments. Tau is a microtubuleassociated protein that stabilizes microtubules and mediates actinmicrotubule interaction. Tauopathies are a heterogeneous groupof neurodegenerative disorders characterized by abnormal protein
aggregation of tau in the brain, including Alzheimer's disease (AD),the most common dementia worldwide, and progressive supranuclear
palsy (PSP), which typically presents postural instability with falls,
supranuclear gaze palsy, and dementia.
Patients with PSP usually die 5–10 years after onset becauseof the lack of effective treatment, and their serious physical andmental disabilities increase their caregiver’s burden. While amyloid-βenhances tau pathology in AD brains, pathological findings of PSP lack
amyloid-β deposits. The molecular mechanism driving abnormal tau
in PSP brains remains inconclusive, and genetic animal models thatphenocopy PSP are unavailable.

FILAMIN-A

Recently, we showed that the actin-binding protein filamin-A isabundant and co-localized with the aggregated tau in the PSP brains(1). We identified duplication of filamin-A gene in monozygotic twin
males concordant for PSP. Our genomic analyses for multiple Japanesecohorts of tauopathy, including J-ADNI and JALPAC, showed that somepatients with PSP and AD have rare variants (minor allele frequency <1%) of filamin-A gene, including seven missense variants (p.S2523N,
p.A2334C, p.V2191M, p.T2101M, p.A2075S, p.A2003H, and p.L1980V)
and one splicing variant (c.4755 + 5G > A). An association study using
the dataset of 312 PSP cases and 499 normal controls demonstrated
that the rare variants of filamin-A gene can contribute to the risk of
PSP with the odds ratio of 3.91.
We also provided biochemical evidence that increased filamin-A
levels enhance the phosphorylation and sarkosyl-insolubility of tau
through interacting actin filaments. Also, reducing filamin-A corrected
aberrant tau levels in the culture cells from cases with PSP. We further
generated an original transgenic mouse expressing human filamin-A(FLNA-Tg). The brains of the 5-month-old FLNA-Tg mice showedsarkosyl-insoluble tau and co-localization of filamin-A with tau in theneurons and glial cells like the PSP brains. Finally, primary corticalneurons from the FLNA-Tg mice showed tau phosphorylation anddefective neurite outgrowth rescued by lentiviral short hairpin RNAmediated knockdown of filamin-A. Our data highlight that filamin-A
promotes tau aggregation, providing a potential mechanism by whichfilamin-A contributes to the PSP pathology.

DRUG DISCOVERY

We filed a patent application (PCT/JP2021/001026) before theindustry-academia collaboration. We are currently evaluating thepotential of filamin-A as a therapeutic target for tauopathy with apharmaceutical company.
Furthermore, we collaborate with Assoc. prof. Ryuji Kato, at
Graduate School of Pharmaceutical Sciences, Nagoya University, andconduct the morphological analysis for filamin-A-overexpressing
neuronal cells using AI-based high-throughput methods to develop
drug screening assay. To generate an animal model for PSP andother tauopathies, we comprehensively analyze the FLNA-Tg
mice by integrated multi-omics approaches, such as epigenomics,
transcriptomics, proteomics, metabolomics, and phenomics.
27 | IAR LETTER | March 2024

Exploring the Potential Applications of Biocatalysts

The 5-month-old FLNA-Tg brains show decreases in the major
neurotransmitter metabolites and a gene expression profile suggestiveof neuronal hyperexcitability in the early phase of neurodegeneration.

INTRODUCTION
Biocatalysts exist in all organisms, including humans, plants,
and microorganisms. Above 3,000 types exist. Enzymes andmicroorganisms are typical biocatalysts. This bioproduction using
biocatalysts can synthesize substances inaccessible through organic
synthesis under ordinary temperature and pressure conditions.
Therefore, biocatalyst-based production (bioproduction)technologies for useful substances are currently attracting
attention in various fields. However, the enzymes involved in an
unstable substance, such as a flavor compound, their metabolites,
and the bioproduction of functional flavor compounds have notbeen established. I have been studying biocatalysts and theirbioproduction involved in flavor compounds.

bacterionanofiber proteins and can be easily immobilized on
various material surfaces [5].

METABOLISM OF FLAVOR COMPOUNDS
Figure 1. Structure and dynamics of filamin-A.
ABD = actin-biding domain, DD = dimerization domain.

BIOPHYSICS

Filamin-A is a dimeric actin filament cross-linking protein with
N-terminal actin-biding domain and 24 immunoglobulin-like repeat
domains (Ig1–24). Ig1–15 is referred to as Rod 1, and 16–23 as Rod 2.
Filamin-A acts as a central mechanotransduction element that converts
mechanical stimuli into chemical signals. For example, mechanicalforce changes the conformation of Rod 2 and its interaction with its
binding partners. Interestingly, tauopathy-associated rare variants offilamin-A are mostly located in Rod 2 (Figure), suggesting that the
perturbation of filamin-A mechanotransduction can be involved in
the pathogenesis of tauopathy. We collaborate with Prof. Takayuki
Uchihashi, at Graduate School of Sciences, Nagoya University, andapply atomic force microscopy to visualize and characterize singlemolecule dynamics of filamin-A.
In addition, we focus on developing mouse models of repetitive
traumatic brain injury (TBI) to understand the mechanical stresstransfer from the brain tissue to the neuronal cytoskeleton and its
effect on the filamin-A mechanotransduction. We also investigate
the involvement of the filamin-A mechanotransduction on chronic
traumatic encephalopathy, a tauopathy in concussed athletes andmilitary veterans with TBI.
Analyzing tauopathy from a biophysics viewpoint offers
unique perspectives on the molecular mechanisms and provide adeeper understanding of the mechanical and dynamic aspects ofneurodegenerative processes to guide the development of therapeutic
approaches.

ACKNOWLEDGMENTS

We thank Prof. Masahisa Katsuno and Assoc. prof. Kentaro

Sahashi at Department of Neurology, Graduate School of
Medicine, Nagoya University, for great support.
REFERENCES[1] Tsujikawa K, Hamanaka K, Riku Y, et al. Actin-binding protein filamin-A
drives tau aggregation and contributes to progressive supranuclear palsy
pathology. Science Advances. 8, eabm5029 (2022).

Flavor compounds are empirically recognized to exhibit“relaxation,” “analgesia,” and “cosmetic effects.” Many ofthese compounds exhibit significant biological activities, andthe non-invasive effects of “fragrance odor” have been widely
expected to prevent and treat diseases. However, volatile oils
containing flavor compounds are found in trace amounts (<0.1%)
in natural products, and their components, flavor properties,
and functionality remain elusive. Furthermore, it is known thatflavor compounds are metabolized by cytochrome P450 (P450
or CYP) and other xenobiotic-metabolizing enzymes after being
taken into the body, but the P450 molecular species involved andthe metabolizing compounds are not elucidated. We extracted
volatile oils from a total of 21 natural products, identified flavor
compounds, and clarified their functionality [1,2]. In addition, wecharacterized the human P450 molecular species involved in themetabolism of xenobiotics in the human liver using microsomes
and 11 molecular species [3]. Moreover, we constructed a libraryof flavor compound-derived metabolites by biotransformation
using different biocatalysts (bacteria and insects) [4].

BIOPRODUCTION OF HIGH-VALUE-ADDED FLAVORCOMPOUND
Bioproduction employing biotransformation is among theways to produce high-value oxygenated derivatives, making
it possible to realize environmentally safe, energy-saving, andregio- and stereo-selective production under mild conditions. In
particular, gas-phase bioproduction, where chemical reactions
proceed in the gas phase using immobilized biocatalysts, isattracting researchers' attention as a green process. However,biocatalysts are usually more unstable than chemical catalysts
and require stabilization techniques, such as immobilization
operations. We overcame this problem by constructing a gas-phasebioproduction system by metabolically engineering the Gramnegative bacterium Acinetobacter sp. Tol5, which has adhesive

Figure. Utilization of Biocatalysts Targeting Naturally Occurring Compounds

FUTURE FOCUS
My research focuses on the biotransformation of nonnaturally occurring compounds, such as nanocarbons.
Nanocarbons have been the most active research area of materials
in recent years, and biotransformation using microorganisms
and purified enzymes has been attempted from the viewpointof green technology. However, dealing with an individually
distinguishable and identifiable single “molecule” has beendifficult since most nanocarbons are mixtures of different sizes
and structures. Moreover, using biocatalysts with nanocarbons
as substrates is only for biodegradation. Therefore, I will develop
a biotransformation system using single molecular nanocarbons
as substrates to produce valuable compounds. Therefore, we can
expect breakthrough results as an approach to implement the
production of useful compounds while considering environmental
conservation.

REFERENCES[1] Usami A., Motooka M., Takagi A., Nakahashi H., Okuno Y., Miyazawa M., J.
Oleo Sci., 63, 723-730 (2014).
[2] Usami A., Motooka R., Nakahashi H., Marumoto S., Miyazawa M., Chem.
Biodivers., 12, 1734-1745 (2015).
[3]Nakahashi H., Yamamura Y., Usami A., Rangsuvigit P., Malakul P.,
Miyazawa M., Biopharm. Drug Dispos., 36, 565-574 (2015).
[4] Usami A., Motooka R., Miyazawa M., Biocatal. Biotrans., 32, 285-289 (2014).
[5] Usami A., Ishikawa M., Hori K., Green Chem., 22, 1258-1268 (2020).

March 2024 | IAR LETTER | 28

Research Highlights _ 09

Observation of Mg-intercalated GaN Superlattice
Nanostructures
Jia WANG

IARCore Faculty Committee

The IAR Core Faculty Committee is composed of the Institute Director, Deputy
Directors, Full-Time Faculty Members, and member of the clerical staff, who promote
the Institute’s activities, and make proposals to the IAR Committee.

Kunio AWAGA

Yoshitaka ITOW

Affiliation : Director of Nagoya IAR /Professor of the Graduate school of
ScienceResearch Field : Solid-State Chemistry

Affiliation : Deputy Director of Nagoya
IAR / Professor of Institute forSpace-Environmental Research
Research Field : Cosmic ray physics,
Neutrino and dark matter

Hitoshi SAKAKIBARA

Hiroko TAKEDA

Affiliation : Deputy Director of Nagoya
IAR / Professor of the Graduate School of
Bioagricultural Sciences
Research Field : Molecular Plant
Physiology, Phytohormone

Affiliation : Deputy Director of Nagoya
IAR / Professor of the Graduate School of
Law
Research Field : Political Sociology, Politics

Yukinori KAWAE

Satomi KANNO

Affiliation : Associate Professor at Nagoya
IAR
Research Field : Egyptian Archaeology,
Pyramid, 3D Survey

Affiliation : Associate Professor at Nagoya
IAR
Research Field : Plant Physiology, Plant
nutrients

Tsutomu FUKUDA

Tatsuro AYATUSKA

Affiliation : Designated Lecturer at
Nagoya IAR
Research Field : Particle Physics,
Astrophysics

Affiliation : Science Communicator
Research Field : Science Communication

Designated Assistant Professor of Young Leaders Cultivation Program
Institute of Materials and Systems for Sustainability / Institute for Advanced Research, Nagoya University
E-mail: wang.jia.t4@f.mail.nagoya-u.ac.jp

INTRODUCTIONOBSERVATION OF MIGS

Recently, we discovered that a monolayer of Mg atoms (or atwo-dimensional (2D) Mg sheet) spontaneously intercalates into the
GaN lattice, forming a so-called 2D Mg-intercalated GaN superlattice(MiGs) nanostructure, as shown in Figure 1. Typically, intercalationis crucial for creating artificial layered structures, with applications
found in the exfoliation of two-dimensional materials, energy
storage, superconductivity, and thermal conductivity control. Twodimensional materials are often chosen as host materials for theintercalation process due to their weak van der Waals layers, whichallow easy insertion of foreign atoms, ions, and molecular sheets
without inducing excessive strain. Conversely, intercalating atomic
sheets into single-crystal ceramics with strong ionic or covalent bonds,
such as semiconductor materials with a wide bandgap, was believed to
be challenging. Yet, in this study, Mg metal was found to intercalate
into the hexagonal wurtzite structure of GaN, creating a uniquestate wherein a monatomic Mg layer or two-dimensional Mg layerintercalates every few GaN layers, forming a superlattice. Such metalintercalation into semiconductor is the first of its kind observation in
the world. As shown in Figures 1d and 1e, Mg occupies the C position(interstitial site) in the otherwise ABAB stacking arrangement ofwurtzite-type GaN. The existence of the two-dimensional metallic Me
sheet was confirmed by Figure 1d and other associated figures.

ASSOCIATED PHYSICAL EFFECTS

In general, uniaxial compressive strain along the c-axis of wurtzitetype GaN can modify its band structure. This change can induceinteresting physical effects beneficial for energy-saving technology
in power device applications, such as an increase in the state densityof the valence band, hole concentration, hole mobility, and thermal
conductivity. In group III nitrides, hole mobility and transport arelimited because of the high electron affinity of nitrogen atoms andweak spin-orbit interaction, leading to a considerable effective mass
for holes. However, applying significant strains to the wurtzite GaN
lattice can reverse the valence band structure, resulting in a split hole

29 | IAR LETTER | March 2024

a

b

c

d

e

Figure 1. 2D Mg-intercalated GaN superlattice (MiGs) nanostructures: a-c, Highangle annular dark field scanning transmission electron microscope (HAADF-STEM)
images with different magnifications. d, Atomically resolved integrated differential
phase contrast (iDPC)-STEM image showing the relative positions of N, Ga and Mg
atoms. e, Schematic illustration of a repeating unit of the MiGs nanostructure.of
the MiGs nanostructure.

band with a light effective mass of holes at the top of the valenceband. This leads to an accumulation of holes in the split-off hole band,
enhancing hole mobility. Specifically, when a uniaxial compressive
strain of -4.3% in the c-axis direction is applied to wurtzite GaN, firstprinciples calculations indicate a hole mobility of 200cm2/(V・s) at room
temperature. The increase in hole mobility due to the reversal of thecrystal field splitting energy has long been sought after, especiallysince introducing high strain into the GaN lattice is challenging. The
MiGs nanostructure appears most promising for achieving high holemobility and concentration simultaneously. Additionally, strained
GaN is theoretically predicted to increase thermal conductivity inthe direction of uniaxial compressive strain. Moreover, since thesuperlattice structure results from the spontaneous diffusion of
Mg into GaN under high temperature and atmospheric pressure,
we believe this structure to be thermodynamically stable under abroad range of conditions. Our next phase of research will focus on
enhancing our understanding of superlattices formed from dissimilarmaterials, like wide bandgap semiconductors and metals. We aim to
explore effects such as hole mobility enhancements by strain-induced
valence band inversion and polarization-induced hole doping due topolarity inversion, and their technological implications – including
Ohmic contacts to p-type GaN and AlN. This knowledge will contributeto the development of innovative electronic devices, like deep
ultraviolet light emitters and p-channel power transistors, leveraging

the potential of wide and ultra-wide bandgap semiconductormaterials.

ACKNOWLEDGEMENT

I would like to acknowledge the support by Japan Scienceand Technology Agency (JST) as part of Advanced International
Collaborative Research Program (AdCORP), Grant Number
JPMJKB2303.
REFERENCES[1]Amano, H. Nobel Lecture. Reviews of Modern Physics 87, 1133 (2015).
[2]Wang, W., Lu, S. & Cai, W. et al., Ohmic Contact to p-Type GaN Enabled by
Post-Growth Diffusion of Magnesium. IEEE Electron Device Letters 43, No.1,
150-153 (2021).
[3]Poncé, S., Jena, D. & Giustino, F. Route to High Hole Mobility in GaN via
Reversal of Crystal-Field Splitting. Physical Review Letters 123, (2019).

IAR
Steering Committee

The IAR Steering Committee plan, discuss, and decide on the Institute’s academic
activities.

Kenji KADOMATSU

Kumiko KATO

Affiliation : Vice President of Nagoya
University / Professor of the Graduate
School of Medicine
Research Field : Biochemistry

Affiliation : Professor of the Graduate
School of Humanities
Research Field : Southeast Asian History,
Tai History

Shigeki KIYONAKA

Kazuhiro NAKAMURA

Affiliation : Professor of the Graduate
School of Engineering
Research Field :Chemical Biology

Affiliation : Professor of the Graduate
School of Medicine
Research Field : Autonomic Neuroscience,
Physiology

Hiroshi OHTA

Akihiko YANASE

Affiliation : Steering Committee /Professor of the Graduate School ofMathematics
Research Field : Mathematics, Geometry

Affiliation : Professor of the Graduate
School of Economics
Research Field : International economics,
Economic theory

March 2024 | IAR LETTER | 30

IAR PEOPLE | IAR Core Faculty Committee / IAR Steering Committee

Gallium nitride (GaN) - a wide bandgap(WBG) semiconductoris widely used in solid-state lighting and holds significant potential
as power electronics alternatives to silicon. It is one of the essential
semiconductors for realizing a carbon-neutral society. Generally,
doping and carrier transport play pivotal roles in the operation ofsemiconductor devices. For various functionalities, realizing not only
n-type but also p-type realization is essential. Since the demonstrationof p-type GaN through magnesium (Mg) doping during epitaxial
growth and electron beam irradiation at Nagoya University more than
30 years ago, there has seen rapid and comprehensive development.
However, like many of today's WBG semiconductor materials, GaN still
struggles with insufficient hole concentration and mobility, posing
significant challenges for societal implementation. On the other hand,the physical and electrical behaviors of Mg, the only acceptor-type
dopant impurity for GaN up to now, have gradually been clarified.
Nevertheless, the relationship between GaN and Mg remains a
captivating tale of mystery.

YLC
Program Faculty
Aaron CHAN

Yoko MIZUTA

Affiliation : Designated Assistant professor
at Nagoya IAR and Graduate School ofMathematics
Research Field : Representation theory,
category theory

Affiliation : Designated Assistant professor
at Nagoya IAR and Institute ofTransformative Bio-Molecules (ITbM),
Nagoya University
Research Field : Molecular biology, Plant
reproduction

Manabu BESSHO-UEHARA

Hanako HAGIO

Affiliation : Designated Assistant professor
at Nagoya IAR and Graduate School of
ScienceResearch Field : Biology, Evolution,
Bioluminescence

Affiliation : Designated Assistant professor
at Nagoya IAR and Graduate School of
Bioagricultural Sciences
Research Field : Fish Neuroscience

Akira YOSHINARI

Fanny BELLEGARDE

Affiliation : Designated Assistant Professor
at Nagoya IAR and Institute ofTransformative Bio-Molecules Sciences
Research Field : Plant Biology

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
Bioagricultural Sciences
Research Field : Plant nutrition, Hormone
biosynthesis, Epigenetic

Satoshi IKEGAYA

Shohei IYOSHI

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School ofEngineering
Research Field : Condensed Matter Physics(Theory)

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
Medicine
Research Field : Cancer Biology, Chemical
Biology

Keiko KAWANO

Shohei SAGA
Affiliation : Designated Assistant Professor
at Nagoya IAR and Kobayashi-Maskawa
Institute (KMI)
Research Field : Observational cosmology

Hisashi HAYAKAWA

Tomoya NAKAYAMA

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
Humanities
Research Field : Art Philosophy

Affiliation : Designated Assistant professor
at Nagoya IAR and Institute forSpace-Earth Environmental Research
Research Field : Space Weather, History,
Solar Activity

Affiliation :Designated Assistant professor
at Nagoya IAR and Graduate School of
Bioagricultural Sciences
Research Field : Animal physiology,
Molecular biology

Yuki SUGIYAMA

Koyo TSUJIKAWA

Ryo HIGUCHI

Minoru HIROSE

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
ScienceResearch Field : Plant Cell Biology

Affiliation : Designated Assistant professor
at Nagoya IAR and Graduate School of
Humanities
Research Field : History of Architecture

Affiliation : Designated Assistant professor
at Nagoya IAR and Graduate School ofMathematics
Research Field : Number Theory

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
Medicine
Research Field : Neurology, Genome
biologyAtsushi USAMI

Jia WANG

Affiliation : Designated Assistant Professor
at Nagoya IAR and Institute ofTransformative Bio-Molecules (ITbM)
Research Field : Biotechnology

Affiliation : Designated Assistant Professor
at Nagoya IAR and Institute of Materials
and Systems for Sustainability (iMaSS)
Research Field : Novel P-type Doping of
Nitride Semiconductors

Jie HUANG

Matthew Paul SU

Affiliation : Designated Assistant professor
at Nagoya IAR and Graduate School of
Humanities
Research Field : Cultural anthropology

Affiliation :Designated Assistant professor
at Nagoya IAR and Graduate School of
ScienceResearch Field : Mosquito neuroscienceand behavior

Yuichiro TADA

Hirotaka IIJIMA

Affiliation : Designated Assistant professor
at Nagoya IAR and Graduate School of
ScienceResearch Field : Early Universe

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
Medicine
Research Field : Rehabilitation medicine,
Mechanobiology, Aging, Systems biology

Sanae ITOElena KOZGUNOVA

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
Humanities
Research Field : Assyriology

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
ScienceResearch Field : Plant cell division

Masamichi MIYAJI

Hideki UMEHATA

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
ScienceResearch Field : Theoretical Physics

Affiliation : Designated Assistant Professor
at Nagoya IAR and Graduate School of
ScienceResearch Field : Astronomy, Astrophysics

IAR
Visiting Professor & Associate Professor
Takaho ANDO

Yasuro ABE

Affiliation : Visiting Professor at Nagoya
IAR / Professor at Chubu University
Research Field : History of Social Thoughts

Affiliation : Visiting Professor at Nagoya
IAR
Research Field : Medieval Japanese
Culture and Texts

Dapeng CAIAtsushi J. NISHIZAWA

Affiliation : Visiting Professor at Nagoya
IAR / Professor at Nanzan University
Research Field : International Economics

Affiliation : Visiting Associate Professor at
Nagoya University /Associate Professor at
Gifu Shotoku Gakuen University
Research Field : Observational Cosmology,
Astronomy

IAR PEOPLE | YLC Program Faculty / IAR Visiting Professor & Associate Professor

IAR PEOPLE | YLC Program Faculty
31 | IAR LETTER | March 2024

Y LC Faculty members are promising young researchers recruited under the
Nagoya University Young Leaders Cultivation Program (YLC Program).

March 2024 | IAR LETTER | 32

IAR
Honorary Directors
Ryoji NOYORI

Yuan Tseh LEE

2001 Winner of the Nobel Prize in
Chemistry University Professor, Nagoya
University Establishment of chirally
catalysed hydrogenation reactions

1986 Winner of the Nobel Prize in
Chemistry Ex-President, ICSU Honorary
Doctorate, Nagoya University Clarificationof the dynamics of chemical elementary
processes

IAR
AcademyIAR PEOPLE | IAR Honorary Directorse / IAR Academy

Hiroshi AMANO

Sumio IIJIMA

2014 Winner of the Nobel Prize in Physics
Professor, Nagoya University Invention ofblue light-emitting diodes

2009 Order of Culture, Japanese
Government Distinguished Invited
University Professor, Nagoya University
Discovery of carbon nanotubes

Tsuneko OKAZAKI

Makoto KOBAYASHI

2021 Order of Culture, Japanese
Government University Professor, Nagoya
University Discovery of Okazaki fragments

2008 Winner of the Nobel Prize in Physics
University Professor, Nagoya University
Discovery of the Kobayashi-Maskawa
theoryShoichi SATO

Kazuo SHINOZAKI

2002 The Japan Academy Prize, Professor
Emeritus, Nagoya University Creation of
the science of textual configuration

2016 Person of Cultural Merit, Japanese
Government University Professor, Nagoya
University Study on molecular mechanismsof stress response in plants

Masahiro SUGIURA

Masatoshi TAKEICHI

2009 Person of Cultural Merit, Japanese
Government University Professor, Nagoya
University Determining the DNA sequenceof the tobacco chloroplast genome

2004 Person of Cultural Merit, Japanese
Government University Professor, Nagoya
University Discovery of Cadherins, themolecular basis governing cellularadhesion

Ryoji NOYORI
2001 Winner of the Nobel Prize in
Chemistry University Professor, Nagoya
University Establishment of chirally
catalysed hydrogenation reactions

33 | IAR LETTER | March 2024

Special Feature about Nagoya University Lecture
The Nagoya University Lecture is the most important lecture series hosted by Nagoya University, inwhich world-class, highly respected researchers are invited to serve as Nagoya University Lecturers. The Nagoya
University Lectures provide an opportunity to experience the world’s best ‘‘knowledge’’. Lectures are awarded thetitle of ‘‘Nagoya University Lectureship,’’ the most prestigious title at Nagoya University. The ‘Kirin’, the motifof the award plaque, is an ancient imaginary spiritual animal that symbolizes wisdom and represents the mostoutstanding person. It overlaps with the presence of the Lecturer. The motif was designed by the artist Nishi
Taiki, is based on a painting preserved in the Shosoin, kept for over 1,200 years as evidence of East-West cultural
exchange, to symbolize the Institute for Advanced Research with a prayer for world peace and academic excellence.

INSTITUTE FOR ADVANCED RESEARCH, NAGOYA UNIVERSITY
Telephone. +81-52-789-3933 E-mail. iar@t.mail.nagoya-u.ac.jp
http://www.iar.nagoya-u.ac.jp/