Changing the world with molecules - Institute of Transformative Bio-Molecules
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Nagoya University Institute of Transformative Bio-Molecules Changing the world with molecules
Contents
Nagoya University
Director's message 4
ITbM at a glance 5
ITbM researchers 6
Research environment 7
Towards globalization 8
Research groups and centers 10
Research achievements 16
Promoting research 24
Graduate Program of Transformative Chem-Bio Research 25
Accomplishments 26
Support and sustainability 27
Contact 28
ITbM's Mix Lab and Mix Office
ITbM's biologists, chemists and theoreticians work side by side in the lab and office (two-layer structure). Connect molecules, create value, and change the world
2 3
Director's message ITbM at a glance
Changing the world with molecules Interdisiciplinary research between chemistry and biology
Molecules are extremely small, but they are essential The identity of ITbM is its capability to develop The Institute of Transformative Bio-Molecules (ITbM) anti-influenza drug, Tamiflu.
to all life on the planet. They are central to the completely new bioactive molecules with carefully at Nagoya University in Japan, is an international
operation of all industries, including pharmaceuticals, designed functions. With biologists knowing what research institute that conducts interdisciplinary At ITbM, chemists, biologists and theoreticians are
agrochemicals, electronic materials, solar cells, functions they need in molecules, and chemists research between chemistry and biology. ITbM was collaborating by working side by side to design and
displays, petrochemicals, automotive manufacturing, knowing how to install these functions, huge selected in October 2012 as one of the centers of synthesize new transformative bio-molecules, and to
plastics, polymers and many other sectors. It is advances are expected from our institute. This the World Premier International Research Center generate a new research area on the boundaries of
my strong belief that molecules have the power to unique approach will surely attract top researchers Initiative (WPI), a ten-year program funded by the chemistry and biology. These endeavors will address
change the way we do science and the way we live. worldwide and also nurture the next generation of Japanese Ministry of Education, Culture, Sports, various social issues regarding the environment, food
researchers who are unrestricted by the bounds of Science and Technology (MEXT). ITbM officially production, and medical technology.
Our dream is to take advantage of the dramatic traditional disciplines. launched in April 2013.
relationship between structure and function. By ITbM has defined the following four flagship
merging state-of-art synthetic chemistry, systems ITbM will connect molecules, create value, and The objective of ITbM is to create a new inter- research areas as the main focus of the institute:
biology, and theoretical science, we aim to develop change the world, one molecule at a time. disciplinary field of research through the collaboration “Chemistry- enabled Live Imaging”, “Chemical
new ways of creating design-based bioactive of cutting-edge synthetic chemistry, animal/plant Chronobiology”, “Plant Chemical Biology”, and “The
molecules with targeted properties. These new Institute of Transformative Bio-Molecules biology, and theoretical science, as well as to deliver Striga Problem”. By exploring a new integrative field
synthetic paradigms will allow the design and Director, Kenichiro Itami bio-molecules that change the way we do science between chemistry and biology, ITbM aims to create
synthesis of bioactive molecules both inside the flask and we live, i.e. “transformative bio-molecules”. transformative bio-molecules through carrying out
and inside living organisms. Most importantly, our chemical biology research to “understand”, “see” and
ultimate goal is to solve urgent problems in science Many transformative bio-molecules have been “regulate” living organisms.
and technology that have a significant impact on developed up to now, such as the discovery of
society. penicillin, and the development of the highly effective
4 5
ITbM researchers Research environment
An international mixture of leading scientists Promoting "mixing" of different fields
ITbM is an international research institute with 13 postdoctoral researchers at ITbM are from overseas, ITbM has set up Mix Labs to remove the physical technology transfer to industries.
principal investigators (PIs), including five overseas and conduct research with graduate students of barriers between research groups and to enhance The ITbM Research Award was established to
PIs, who concurrently hold posts at ITbM and their Nagoya University. This enables researchers to interdisciplinary research across various fields and promote interdisciplinary research proposed by
own institutions. Cooperative PIs (Co-PIs) have integrate with Japanese students, and also have the groups. Unlike traditional labs, where the labs are young researchers working in the Mix Lab. The
been appointed to oversee satellite groups at ITbM, opportunity to learn different cultures while being in usually separated according to research groups, award provides start-up funding and is granted to
and to maintain close contact with the PIs through Japan. the Mix Labs incorporate large spaces, where outstanding collaborative research projects that are
e-mails and regular online meetings. The majority of researchers and students from different backgrounds proposed by a team of researchers from different
share the same space and can have discussions fields, which consist of at least one ITbM researcher
on a daily basis. Each PI is in charge of their own (non-PIs). Many of the selected proposals have
research group. Nevertheless, the flexible interaction become representative projects at ITbM.
ITbM in numbers: *As of April 2019 that exists between different research groups enables ITbM’s new research building that reflects the Mix
13 principal investigators: dynamic mixing of research that goes beyond the Lab concept was completed in March 2015. The
boundaries of conventional frameworks. Using building’s whole area space is 7,934 m 2 and is a
8 from Nagoya University, 5 from overseas institutions
“molecules” as the common keyword has advanced 6-storied building that consists of two sets of Mix
5 chemists, 6 biologists, 2 theoreticians the understanding between different disciplines. Labs and Mix Offices. The labs and offices make
The Mix Labs have played an immense role in up a 2-layer structure, where the Mix Offices are an
30 faculty members, 2 invited faculty members
advancing collaborative interdisciplinary research at open space over the windows that has a good view
32 postdoctoral researchers ITbM, as the faculty, postdoctoral researchers and of the Mix Labs situated below.
34% international researchers students are able to communicate across different The center is also equipped with a kids’ room to
fields and put their research proposals immediately assist researchers with children, as well as refresh
14 countries: into action. Over 20 interdisciplinary research themes spaces, and a wooden deck in order to enable
Canada, China, France, Germany, Hungary, India, Italy, Japan, Korea, Poland, have emerged from young researchers in the Mix interactions between members. ITbM Tea break
Labs, and some of the research outcomes have Meetings are held weekly to facilitate communication
Switzerland, Taiwan, UK, USA already been released as patents and publications, between members of the institute.
as well as commercialization of reagents through
6 7
Institute of Transformative
Bio-Molecules (ITbM),
Nagoya University
Heinrich Heine University Düsseldorf (HHUD) Queen’s University
Düsseldorf, Germany Nagoya, Japan Kingston, Canada
Max Planck Institute
Köln, Germany RIKEN Center for Sustainable
Resource Science (CSRS)
Wako, Japan
ETH Zürich
Zürich, Switzerland
University of Southern California
Los Angeles, USA
Towards globalization The University of Texas at Austin
Austin, USA
International symposia and awards
Academia Sinica National Science Foundation
Nankang, Taiwan Center for Selective
C–H Functionalization
(NSF-CCHF)
15 institutions across USA
ITbM is organizing a number of international Tsuneko & Reiji Okazaki Award
symposia and awards each year. Through these T h e Ts u n e k o & R e i j i O k a z a k i A w a r d w a s
international events, ITbM is establishing a strong established in 2015 by ITbM in memory of the great
network with leading researchers in the fields achievements of Dr. Tsuneko Okazaki, Special
of synthetic chemistry, animal/plant biology and Professor of Nagoya University and the late Dr. Reiji
theoretical sciences. These activities are part of Okazaki, Honorary Professor of Nagoya University.
ITbM’s globalization strategy, which aims to enhance Drs. Okazaki are known for their discovery of the Partnerships and global networks
globalization. Okazaki Fragments, which are short DNA fragments
that are formed during DNA replication, and have
ITbM has collaborations with institutions worldwide. for Sustainable Resource Science (RIKEN CSRS,
International Symposium on Transformative Bio- contributed to advancing the field of molecular
In addition to the universities/institutes where the Center Director: Dr. Kazuo Shinozaki) and Institute
Molecules (ISTbM) biology. Their efforts have also inspired subsequent
overseas PIs hold posts (ETH Zürich, Queen’s of Chemistry, Academia Sinica (Director: Dr. Yu-
ITbM organizes its international symposium each generations of researchers. The Okazaki Award is
University, The University of Texas at Austin, Ju Chen). Joint workshops are held with these
year in Nagoya by inviting world-leading researchers an international award that is presented each year to
University of Southern California, Heinrich Heine collaborating institutes. In addition, student and
who carry out research in ITbM’s related fields. a young leading scientist, who has made significant
University Düsseldorf, and Max Planck Institute), faculty exchanges are ongoing between ITbM and
ISTbM contributes to the establishment of ITbM’s contributions in the field of life sciences through
ITbM is collaborating closely with the National CCHF.
international network and promotes international unique approaches and techniques.
Science Foundation Center for Selective C–H Researchers at Nagoya University who carry out
research collaborations.
Functionalization (NSF-CCHF, Center Director: Dr. research related to ITbM's are also involved as
Nagoya Medal of Organic Chemistry
Huw Davies, Emory University), the RIKEN Center collaborators.
Hirata Award The Nagoya Medal of Organic Chemistry is an
The Hirata Memorial Lecture started in 2005 at international award that was established in 1995
Nagoya University and is an international award by Dr. Ryoji Noyori, Special Professor of Nagoya
granted each year to a rising star in the field of University, and Dr. Hisashi Yamamoto, Honorary
organic chemistry. This award was established in Professor of Nagoya University, under the support of
memory of the great achievements of the late Dr. the MSD Life Science Foundation (previously known
Yoshimasa Hirata, Honorary Professor of Nagoya as the Banyu Life Science Foundation International).
University. Dr. Hirata is known for the discovery Every year, the Nagoya Gold Medal is awarded to
of many natural products, including tetrodotoxin, an organic chemist who has made significant original
a neurotoxin found in puffer fish, and greatly contributions to the field in its broadest sense, and
contributed to the advancement of natural product the Silver Medal is presented to a promising scientist
chemistry. Throughout the years, the Hirata Memorial based in Japan, whose research has had a major
Lecture has been given by many distinguished young impact on the field of synthetic organic chemistry.
chemists and has grown to become an internationally From 2014, ITbM’s director, Dr. Kenichiro Itami,
recognized honor in organic chemistry. From 2015, assumed the role of chairman of the Nagoya Medal,
the Lecture has changed its name to the "Hirata thus ITbM became the organizer of this award.
Award" and is organized by ITbM.
Academia Sinica
Nankang, Taiwan
8 9
Research groups: Chemistry Designing and making molecules
Itami Group Bode Group
Professor Kenichiro Itami Professor Jeffrey Bode
Position Grad. Sch. of Science, Nagoya Univ. Position ETH Zürich, Switzerland
E-mail itami@chem.nagoya-u.ac.jp E-mail bode@itbm.nagoya-u.ac.jp
Education 1998 Dr. Eng.; Kyoto Univ. Education 2001 Dok. Nat. Sci.; ETH Zürich,
Research interests synthetic chemistry, catalytic Switzerland
Faculty members: chemistry, materials chemistry Faculty member: Research interests synthetic chemistry, protein synthesis,
Kei Murakami Shunsuke Oishi
Hobbies sports, ramen, hot spring, Jaguar chemical biology
Hideto Ito (Co-PI)
F-TYPE British Design Edition Place of birth California, USA
Akiko Yagi
Favorite molecule benzene
Kazuma Amaike Research overview: The chemical synthesis of proteins can be accomplished by peptide ligation
Place of birth Pennsylvania, USA
reactions. In our own research, we have developed a new amide-forming reaction of α-ketoacids and
Shinya Hagihara Research overview: The ultimate goal of the Itami group is to develop “transformative molecules”, hydroxylamines (KAHA ligation) that allows the synthesis of proteins by combining peptide segments
(Affiliated researcher)
innovative functional molecules that make a marked change in the form and nature of science and technology. under aqueous conditions without coupling reagents or side chain protecting groups. Rendering the
With such a goal in mind, the work of the Itami group has centered on catalyst-enabling synthetic chemistry synthesis of proteins – including highly modified derivatives and covalent protein–protein conjugates –
with broad directions. The emphasis is on the development of new catalysts for solving challenging synthetic as routine and convenient as bacterial protein expression is the long term goal of our research program.
problems, for realizing super-efficient chemical syntheses, for high demand molecule activations, and for
producing as-yet unexplored molecules of significant interest in various fields.
Ooi Group Crudden Group
Professor Takashi Ooi Professor Cathleen Crudden
Position Grad. Sch. of Eng., Nagoya Univ. Position Queen's Univ., Canada
E-mail tooi@chembio.nagoya-u.ac.jp E-mail cruddenc@chem.queensu.ca
Education 1994 Dr. Eng.; Nagoya Univ. Education 1994 Ph.D.; Univ. of Ottawa, Canada
Research interests organic synthesis and catalysis Research interests asymmetric synthesis, organometallic
Faculty members: Place of birth Aichi, Japan Faculty member: catalysis, nano materials
Kohsuke Ohmatsu Masakazu Nambo
Hobbies swimming, cycling, heavy metal
Daisuke Uraguchi (Co-PI)
Research overview: We have been creating a bold stream of research on the molecular design Favorite molecule BINAP (chiral ligand)
Yoshitaka Aramaki Place of birth Belfast, North Ireland
of various organic ion pairs and their rational structural modifications for eliciting unique functions
Ken Yamanomoto
as molecular catalysts, providing a solid basis for the safe and sustainable supply of useful organic
Research overview: Research in the Crudden group focuses on catalysis and materials chemistry. We are
compounds. At ITbM, we develop innovative molecular catalysts that can revolutionize organic reactions
interested in developing new reactions to prepare interesting organic molecules, in particular reactions
and chemical syntheses in order to not only provide sustainable chemical processes, but also accelerate
that are enantioselective or enantiospecific. With our collaborators at ITbM, we aim to investigate the
the discovery of transformative bio-molecules as a reliable means for solving problems of fundamental
biological activity of these molecules for applications in the pharmaceutical and agricultural industries.
biological significance.
We are also interested in the use of carbon–based molecules as ligands for metal surfaces and
nanomaterials comprised of gold and other metals. With our collaborators at ITbM and other institutions
across the world, we aim to investigate the applications of these materials in various fields, including
catalysis and biological imaging.
Yamaguchi Group
Professor Shigehiro Yamaguchi
Position Grad. Sch. of Science, Nagoya Univ.
E-mail yamaguchi@chem.nagoya-u.ac.jp
Education 1997 Dr. Eng.; Kyoto Univ.
Research interests physical organic chemistry,
Faculty members: fluorescent molecules
Masayasu Taki
Masahito Murai Research overview: We work on a variety of topics in the fields of main group chemistry and physical
Soichiro Ogi organic chemistry. In particular, the emphasis is placed on the construction of new π-conjugated
Naoki Ando scaffolds, which is crucial for pursuing photo/electronic functions of organic molecules. At ITbM, we are
pursuing the challenge of designing and synthesizing transformative fluorescent π-conjugated molecules
Aiko Fukazawa for bioimaging applications. A number of fascinating fluorescent molecules have been developed so far,
(Affiliated researcher) not only for optoelectronic applications like OLEDs (organic light emitting diodes), but also for biological
applications such as fluorescent probes.
10 11
Research groups: Biology Elucidating the function of molecules
Higashiyama Group Kinoshita Group
Professor Tetsuya Higashiyama Professor Toshinori Kinoshita
Position Grad. Sch. of Science, Nagoya Univ. Position Grad. Sch. of Science, Nagoya Univ.
and The Univ. of Tokyo E-mail kinoshita@bio.nagoya-u.ac.jp
E-mail higashi@bio.nagoya-u.ac.jp Education 1994 Dr. Sci.; Kyushu University
Education 1999 Dr. Sci.; The Univ. of Tokyo Research interests plant molecular biology
Faculty members: Research interests plant reproduction, peptides, live cell Faculty members: Hobbies observing & raising living organisms
Minako Ueda imaging Norihito Nakamichi
Narie Sasaki Hobbies driving the car with the family, traveling Yuichiro Tsuchiya Research overview: Our research focuses on understanding the mechanism of how plants adapt and
Masahiro M. Kanaoka Favorite molecule LURE, AMOR Koji Takahashi respond to ever-changing environmental signal. Stomata is the key in this process - since the pair of guard
Daisuke Kurihara Place of birth Yamagata, Japan Yin Wang cells surrounding stomatal pores regulate CO2 uptake for photosynthesis and water loss from leaves in
Hidenori Takeuchi Mizuho Ichinose response to environmental signals. We have been studying signaling pathways responsible of stomatal
Yoko Mizuta Research overview: At ITbM, we strive to produce novel and useful hybrid plants through combination of our Yosuke Toda opening and closing, and have identified the key components that regulate this behavior. To elucidate the
unique live cell biology and synthetic chemistry to generate key molecules responsible for plant reproduction. full signaling pathway of stomatal opening and closing, we are using genetic, biochemical and physiological
Michitaka Notaguchi We have also been a leader in advancing development of relevant molecules and technology for innovative approaches to uncover the full mechanism. Our discovery will allow generation of plants with high productivity
(Affiliated researcher) bioimaging, and have succeeded in establishing a system for live imaging of early plant embryogenesis. and drought tolerance, simply through the regulation of stomatal openings.
We're working towards development of ideal fluorescent molecules suitable for in vivo labeling of specific
components, which allows directly visualization of the dynamics of these signaling molecules deep in the
whole tissue using two-photon microscopes.
Torii Group Yoshimura Group
Professor Keiko Torii
Professor Takashi Yoshimura
Position The Univ. of Texas at Austin and
Position Grad. Sch. of Bioagricultural Sciences,
Howard Hughes Medical Institute, USA
Nagoya Univ.
E-mail torii@itbm.nagoya-u.ac.jp
E-mail takashiy@agr.nagoya-u.ac.jp
Education 1993 Ph.D.; Univ. of Tsukuba
Faculty members: Education 1996 Dr. Agr.; Nagoya Univ.
Research interests plant development, cell-cell
Naoyuki Uchida Faculty members: Research interests animal integrative physiology,
communication, peptides
(Co-PI) Taeko Ohkawa chronobiology, systems biology
Hobbies art (illustration), music (choir and orchestra)
Soon-Ki Han Yusuke Nakane Hobbies traveling, visiting museums, sports
Favorite molecule LRR-RLK (plant kinase receptor), caffeine
Favorite molecule DHEA (anti-aging supplement)
Place of birth Tokyo, Japan
Place of birth Shiga, Japan
Research overview: In the Torii-Uchida group, we strive to probe signaling dynamics and manipulate
plant development via integrated approaches of synthetic cell biology, chemical biology and molecular Research overview: Cyclic environmental changes such as day-night and seasonal cycles control all
genetics. Fully leveraged on ITbM’s core strengths and ambitious mission to fuse catalysis chemistry organisms on earth. To better adapt to these cyclic events, organisms have developed internal biological
and plant & animal biology, we aim to: (i) design small molecules to highjack inter- and intra-cellular clocks during the evolutionary process. To understand animals’ clever adaptation strategies to environmental
signaling networks; and develop fluorescent probes to visualize signaling dynamics (synthetic cell changes, we apply interdisciplinary approaches to various animals that have highly sophisticated mechanisms.
biology); (ii) design and screen for small molecules to manipulate plant growth (chemical biology); and (iii) Our findings are currently fueling development of transformative bio-molecules that will improve animal
elucidate the functions of ligand-receptor pairs in plant development, with a specific focus on the EPF- production and human health.
peptides and ERECTA family receptors (developmental genetics).
Frommer Group Kay Group
Professor Wolf B. Frommer Professor Steve Kay
Position Heinrich Heine Universität Düsseldorf and Max Planck Institute for Breeding Position Univ. of Southern California, USA
Research, Germany E-mail kay@itbm.nagoya-u.ac.jp
E-mail wfrommer@itbm.nagoya-u.ac.jp Education 1984 Ph.D., Univ. of Bristol, UK
Education 1987 Dr. rer. nat.; University of Köln, Germany Research interests chronobiology, chemical biology
Faculty member: Research interests molecular biology, biochemistry, chemical genomics Faculty member: Hobbies tuna fishing
Masayoshi Nakamura Hobbies traveling to Japan, motorcycle riding, skiing, martial arts, sweets Tsuyoshi Hirota Place of birth Jersey, UK
(Co-PI) Favorite molecule isorhamnetin-3-O-β-D-glucopyranoside (Co-PI)
Place of birth somewhere in Germany Research overview: By using the resources of clock modifying compounds and genes in combination with
state-of-the-art technologies at ITbM, the Kay-Hirota group aims to discover “transformative bio-molecules”
Research overview: The research in the Frommer group at ITbM is carried out in the following four that will revolutionize clock research and ultimately benefit human health. A unique combination of molecular,
areas: (i) engineering of genetically encoded biosensors and sponges for in vivo biochemistry; (ii) genetic, genomic, biochemical, and chemical biology approaches will allow us to reveal key regulatory
characterization of the determinants of interactions between small molecules and transporters to help processes of the circadian clock and define molecular links between the clock and rhythmic regulation of
identifying novel drugs and agrochemicals; (iii) search for yet unidentified receptors for small molecules; physiology and behavior. Proof-of-concept chemical probes will provide useful tools to control clock function
and (iv) chemical genomics and imaging of processes related to cellular growth and dynamics. in a conditional manner and also act as starting points for developing therapeutics for circadian clock-related
disorders.
12 13
Research groups: Theory Centers
Calculating and analyzing molecules Accelerating ITbM's interdisciplinary research
Tama Group Live Imaging Center Chemical Library Center
Professor Florence Tama
Designated Associate Professor Designated Associate Professor
Position Grad. Sch. of Science, Nagoya Univ.
Yoshikatsu Sato Ayato Sato
E-mail florence.tama@nagoya-u.ac.jp
Education 2000 Ph.D.; Univ. Paul Sabatier, France E-mail: E-mail: ayato-sato@itbm.nagoya-u.ac.jp
Research interests computational biophysics sato-yoshikatsu@i.mbox.nagoya-u.ac.jp
Hobbies traveling, movies
Place of birth Carmaux, France
Research overview: Research in the Tama group focuses on the computational studies of structures
and functions of large macromolecular assemblies. Dysfunctions of these bio-molecules may result Center overview: The Live-imaging Center provides Center overview: Focusing on creating bioactive hit molecules
in severe diseases, and in order to understand such diseases and develop treatments, the functional access of advanced optical microscopes to everyone–from for specific biological phenomena. The Chemical Library
ITbM members to researchers worldwide. We have many Center is the pioneer of collaborative research at ITbM.
mechanisms of these bio-molecules need to be elucidated. To this goal, Tama’s group 1) develops new
cutting-edge microscopes and equipments, including; (1) With approximately 70,000 compounds available, the center
computational techniques to determine 3D structures and dynamics of biological complexes; and 2)
multifunctional laser scanning system for spectral imaging expanding the unique libraries with selected natural products,
works in collaboration with experimental groups to elucidate functions of bio-molecules of interest.
with ultimate sensitivity, multi-photon imaging, and high speed pharmaceuticals drugs, and novel synthetic compounds. The
imaging; (2) laser microdissection; (3) optical tweezers; (4) center is equipped with an automated chemical dispensing
Infrared evoked gene operation system (IR-LEGO) equipped machine, clean bench, incubators and high performance liquid
with (5) laser thermal micro-injector and (6) pico-pipette for chromatography-mass spectrometer, which are relevant to
Yanai Group collecting small volumes; (7) light sheet microscope; (8) STED
superresolution system equipped with (9) fluorescence lifetime
conduct chemical biology research. It works as a hub where
synthetic chemists bring the molecules that they have designed
Professor Takeshi Yanai imaging. In addition to the supporting activities for our users, and synthesized and the biologists use the molecules for
our mission is developing transformative bioimaging molecules their assays. Up to now, the center has been providing over
Position Grad. Sch. of Science, Nagoya Univ. by collaborating with Yamaguchi, Itami, and Higashiyama 1,200,000 compounds to over 85 collaborators. A new style
E-mail yanait@chem.nagoya-u.ac.jp group. Furthermore, we also study our own research about the of an interdisciplinary research is recently arising, where the
Education 2001 Dr. Eng.; The Univ. of Tokyo plant cell physiology in response to the environmental stimuli. chemists propose novel biological assay methods using the
Research interests computational quantum chemistry small molecules that they have designed based on feedback
Faculty members: Hobbies programming, starbucksing, camping from the biologists.
Kazuhiro Fujimoto Favorite molecules Nitrogen molecule and chromium
Masaaki Saitow dimer
Place of birth Shimane, Japan Molecular Structure Center Peptide Protein Center
Research overview: The heart of chemistry lies in the transformation of molecules. In the Yanai
group, we investigate transformations of molecular systems through theoretical and quantum chemistry Designated Assistant Professor Designated Assistant Professor
computational methods. The prime goal of our research is to elucidate the principals and mechanisms Keiko Kuwata Shunsuke Oishi
guiding chemical transformations, while recognizing the importance of the role of electrons in these E-mail: kuwata@itbm.nagoya-u.ac.jp E-mail: oishi@itbm.nagoya-u.ac.jp
systems.
Center overview: The Molecular Structure Center is equipped Center overview: The Peptide Protein Center provides tailor-
with cutting-edge machines for structural determination of made peptides and proteins to ITbM’s biology groups. Using
organic and biological molecules synthesized by members of ligation chemistry developed by ITbM's Bode group, we can
ITbM. Numerous top-notch machines are available to facilitate prepare linear peptides, cyclic peptides, and synthetic proteins.
members of ITbM: (1) X-ray diffractometer with a Super Bright The peptides and proteins prepared can be tailored to suit
X-ray generator; (2) Super high resolution NMR machine different needs; We have successfully incorporated novel
equipped with a probe that can be cooled to the temperature fluorescent molecules developed the Yamaguchi group, and
of liquid helium and nitrogen (UltraCOOL-, SuperCOOL- unnatural amino acids synthesized by the Ooi group into
NMR); (3) High performance liquid chromatography mass synthetic peptides and proteins. We envision that these unique
spectrometer equipped with a nanospray unit for proteomics compounds would be transformative for the biological studies
analysis (nanoLC-MS/MS); (4) High performance liquid in ITbM.
chromatography-mass spectrometer equipped with an
electric field Fourier transformation spectrometer for high
accuracy metabolomics analysis (LC-MS); (5) MALDI imaging
spectrometer (MALDI-TOF/TOF); and (6) Hydrogen/deuterium
exchange mass spectrometer for protein interaction analysis State-of-the-art equipment are available in all centers.
(HDX-MS). External access to the four centers can be arranged
upon request.
14 15
Research achievements 2 Stomata for plant growth and development
1 Combating the plant parasite, Striga 1 Enhancement of photosynthesis and plant growth
through the promotion of stomatal opening:
By determining the key factor in regulating photosynthesis and
plant growth, Professor Toshinori Kinoshita and his group have
A step forward towards improving crop production and succeeded in developing a method to increase photosynthesis
reducing atmospheric CO2 (CO2 uptake) and plant growth through the promotion of stomatal
1 Sphinx molecule to rescue African farmers from develop a molecule, SPL7, that forcibly germinates Striga opening in the model plant, Arabidopsis thaliana. Enhanced
witchweed seeds at extremely low concentration. SPL stimulates Striga stomatal opening was achieved by overexpressing the plasma
germination at femtomolar (10-15 M) range, yet only bound to membrane H+-ATPase (enzyme) in guard cells surrounding the
the strigolactone receptor in Striga. The potency is on par with stomata. The study is expected to contribute to the promotion of
Despite its beautiful purple-pink flowering, Striga is a major natural strigolactone, 5-deoxystriogl, which is the strongest plant production and towards the development of a sustainable
threat for food crops affecting global food security. Striga is germination stimulant to Striga among all commercially low carbon society.
a parasitic plant that mainly affects Africa, where its roots available compounds. References:
deprive host crop plants (rice and corn) from their nutrients. "Overexpression of plasma membrane H+-ATPase in guard cells promotes
The host plant eventually withers, leading to yield losses Field trials of SPL7 to control Striga growth in a field located in light-induced stomatal opening and enhances plant growth" by Yin Wang,
in approximately 40 million hectares of land, worth over 10 Kenya are ongoing. Ko Noguchi, Natsuko Ono, Shin-ichiro Inoue, Ichiro Terashima, and Toshi-
billion U.S. dollars, which affects over 100 million people. Yet, nori Kinoshita, PNAS 2013, 111, 533. DOI: 10.1073/pnas.1305438111
the full mechanism on how Striga detects the presence of the Reference:
"A Raf-like protein kinase BHP mediates blue light-dependent stomatal
host plants has been unclear and efforts are being made to "A femto-molar range suicide germination stimulant for the parasitic plant
opening" by Maki Hayashi, Shin-ichiro Inoue, Yoshihisa Ueno, and Toshinori
develop new methods to combat Striga. Striga hermonthica" by Daisuke Uraguchi, Keiko Kuwata, Yuh Hijikata,
Kinoshita, Sci. Rep. 2017, 7, 45586. DOI: 10.1038/srep45586
Rie Yamaguchi, Hanae Imaizumi, Sathiyanarayanan AM, Christin Rakers,
Dr. Daisuke Uraguchi (Ooi Group), Dr. Yuichiro Tsuchiya Narumi Mori, Kohki Akiyama, Stephan Irle, Peter McCourt, Toshinori
Kinoshita, Takashi Ooi, Yuichiro Tsuchiya, Science 2018, 362, 6420. DOI:
(Kinoshita Group), and their groups have come together to 2 More mouths can be fed by boosting number of plant Professors Keiko Torii, Kenichiro Itami and their groups have
pores: Discovery of small molecules that increases the synthesized a new bioactive small molecule that has the ability
number of stomata on plant leaves to increase stomata numbers on flowering plants (Arabidopsis)
without stunting their growth. Molecules were synthesized
using a rapid palladium-catalyzed C–H arylation methodology
developed by the Itami group. The team's new discovery could
help elucidate the stomatal development mechanism in plants.
References:
"Discovery of synthetic small molecules that enhance the number of
stomata: C–H functionalization chemistry for plant biology" by Asraa Ziadi,
Naoyuki Uchida, Hiroe Kato, Rina Hisamatsu, Ayato Sato, Shinya Hagihara,
Kenichiro Itami and Keiko U. Torii, Chem. Commun. 2017, 53, 9632. DOI:
10.1039/C7CC04526C
3 Scientists reveal why plant stomata has its particular Professor Keiko Torii and her collaborators have revealed the
lip shape: Stomata's master regulator gene MUTE mechanism on how stomata in land plants are formed through
demonstrates how organisms develop their shape a single symmetric cell division. The scientists discovered
that a gene in plants known as MUTE orchestrates stomatal
development. As the regulation style by the MUTE gene can be
observed in a similar manner in the gene expression mechanism
of animals and enzymes, this research provides insight to how
various organisms have developed their shape. Developmental
regulation of the stomata is expected to contribute towards crop
improvement.
References:
"MUTE Directly Orchestrates Cell-State Switch and the Single Symmetric
Division to Create Stomata" by Soon-Ki Han, Xingyun Qi, Kei Sugihara,
Jonathan H. Dang, Takaho A. Endo, Kristen L. Miller, Eun-Deok Kim,
Takashi Miura, Keiko U. Torii, Dev. Cell 2018, 45, 303. DOI: 10.1016/
SL-like molecules work as inducers of suicidal germination to purge the soil of viable Striga seeds before planting the crop seed.
j.devcel.2018.04.010
4 Discovery of compounds that keep plants fresh: Professor Toshinori Kinoshita and his team have discovered
Controlling plant pore openings for drought tolerance and new compounds that can control stomatal movements in plants.
delay in leaf withering Some of the compounds have shown to prevent leaves from
drying up and suppress withering when sprayed onto rose and
oat leaves. Further investigation could lead to the development of
new compounds that can be used to extend the freshness of cut
flowers and flower bouquets.
References:
"Identification and Characterization of Compounds that Affect Stomatal
Movements" by Shigeo Toh, Shinpei Inoue, Yosuke Toda, Takahiro Yuki,
Kyota Suzuki, Shin Hamamoto, Kohei Fukatsu, Saya Aoki, Mami Uchida,
Rose leaves sprayed with stomata closing compound (SCL) withered less Eri Asai, Nobuyuki Uozumi, Ayato Sato and Toshinori Kinoshita, Plant Cell
compared to rose leaves without spraying (control) after 8 hours. Physiol. 2018, 59, 1568. DOI: 10.1093/pcp/pcy061
Kenya Agricultural & Livestock Research Organization (KALRO)
Kisumu, Kenya
16 17
3 Pollen tube attraction and fertilization 4 Plant growth and morphology
1 AMOR, a love potion for plant fertilization: Professor Tetsuya Higashiyama and his group have 1 Cell fusion 'eats up' the 'attractive cell' in flowering Flowering plants naturally know when they need to spare
Discovery and synthesis of AMOR sugar chains that succeeded in discovering AMOR (Activation Molecule for plants: Solving the mystery of the progression of or eliminate their cells. An international team led by Dr.
activate pollen tube Response-Capability), a sugar chain molecule that increases fertilization in Arabidopsis by live cell imaging Daisuke Maruyama and Professor Tetsuya Higashiyama, has
the fertilization efficiency in Torenia fournieri plants. AMOR examined plant cells of the ovule by live imaging to reveal
was found to be responsible for activating pollen tubes leading a novel cell-elimination system based on an unusual cell
to fertilization. The word AMOR is taken from the Latin word fusion, thereby uncovering the mechanism by which flowering
for "love" and "cupid", thus illustrating its function of bringing plants prevent further attraction of multiple pollen tubes after
female and male organs together. Through collaboration with successful fertilization.
Professor Kenichiro Itami's group, the team has synthesized References:
a disaccharide, i.e. a double sugar, which exhibits the same "Rapid elimination of the persistent synergid through a cell fusion
properties as AMOR. This discovery is expected to lead to mechanism" by Daisuke Maruyama, Ronny Völz, Hidenori Takeuchi,
advances in improving plant fertilization efficiency as well as Toshiyuki Mori, Tomoko Igawa, Daisuke Kurihara, Tomokazu Kawashima,
open new doors in carbohydrate chemistry for applications in Minako Ueda, Masaki Itoh, Masaaki Umeda, Shuh-ichi Nishikawa, Rita
plant science. Groß-Hardt and Tetsuya Higashiyama, Cell 2015, 161, 907. DOI: 10.1016/
A novel cell to cell fusion in a fertilized ovule in Arabidopsis thaliana j.cell.2015.03.018
References:
"The AMOR arabinogalactan sugar chain induces pollen-tube competency
to respond to ovular guidance" by Akane G. Mizukami, Rie Inatsugi,
Left: Pollen tube activation with AMOR (in Torenia fournieri)
Right: Structure of AMOR disaccharide Jiao Jiao, Toshihisa Kotake, Keiko Kuwata, Kento Ootani, Satohiro
Okuda, Subramanian Sankaranarayanan, Yoshikatsu Sato, Daisuke 2 Three rings stop cell division in plants: Drs. Minako Ueda and Masakazu Nambo and their team have
Maruyama, Hiroaki Iwai, Estelle Garénaux, Chihiro Sato, Ken Kitajima, Development of a triarylmethane compound for possible succeeded in developing a new compound, a triarylmethane,
Yoichi Tsumuraya, Hitoshi Mori, Junichiro Yamaguchi, Kenichiro Itami, control of plant growth that can rapidly inhibit cell division in plants. This compound
Narie Sasaki and Tetsuya Higashiyama, Curr. Biol. 2016, 26, 1091. DOI: was found to selectively inhibit cell division in plant cells versus
10.1016/j.cub.2016.02.040
animal cells, and shows reversible inhibitory properties. This
triarylmethane could therefore be a potential candidate for
developing into an agrochemical for the selective control of plant
growth..
2 Where males sense females in plants: Pollen tubes are attracted by LURE peptides, which are References:
"Combination of Synthetic Chemistry and Live-Cell Imaging Identified
Unraveling the unknown receptors and mechanism for produced from ovules, to bring about fertilization. Dr. Hidenori
a Rapid Cell Division Inhibitor in Tobacco and Arabidopsis thaliana" by
fertilization in plants Takeuchi and Professor Tetsuya Higashiyama have now Masakazu Nambo, Daisuke Kurihara, Tomomi Yamada, Taeko Nishiwaki-
revealed for the first time, the receptor in pollen tubes that Ohkawa, Naoya Kadofusa, Yusuke Kimata, Keiko Kuwata, Masaaki
Structure of a cell division inhibitor (triarylmethane) and images of cell division
is required to detect LURE in the model plant, Arabidopsis activity in plant cells. Arrows show cells arising from cell division. (-): Cells Umeda and Minako Ueda, Plant Cell Physiol. 2016, 57, 2255. DOI:
thaliana. The discovery of this unknown mechanism of plant without the addition of the inhibitor ; (+): Cells with addition of the inhibitor 10.1093/pcp/pcw140
fertilization may allow for improvements in the efficiency of
pollen tube growth to be made, resulting in an increased
success rate of fertilization. In addition, this study may also 3 Unlocking the mystery on how plant leaves grow their Dr. Naoyuki Uchida, Professor Keiko Torii and their group
generate new methods to enable cross-fertilization between
teeth: Discovery of EPFL2 peptide (key) and its receptor have discovered the key element, an EPFL2 peptide, that is
different plant species to generate new crops.
(lock) that make zigzag edges on leaves responsible for creating the teeth-like shapes on plant leaves.
The zigzag edges of leaves, so-called leaf teeth, are important
for making the characteristic shapes of each leaf. This study
References: illustrates the unexplored mechanism of leaf teeth formation and
Left: Capsella rubella "Tip-localized receptors control pollen tube growth and LURE sensing will shed light on how leaves have developed to become the
Right: C. rubella pollen tube attraction to Arabidopsis thaliana LURE in Arabidopsis" by Hidenori Takeuchi and Tetsuya Higashiyama, Nature shapes that they are today.
before (top) and after (bottom) introducing A. thaliana PRK6 2016, 531, 245. DOI: 10.1038/nature17413
References:
"A secreted peptide and its receptors shape the auxin response pattern
and leaf margin morphogenesis" by Toshiaki Tameshige, Satoshi Okamoto,
Jin Suk Lee, Mitsuhiro Aida, Masao Tasaka, Keiko U. Torii and Naoyuki
Uchida, Curr. Biol. 2016, 26, 2478. DOI: 10.1016/j.cub.2016.07.014
3 Unlocking the mystery of pollen tube guidance: Pollen tube guidance towards the ovule is an important step
Solving the cocrystal structure of a pollen tube attractant for fertilization in flowering plants. In order for this to happen,
and its receptor a pollen tube attractant peptide LURE guides the pollen tube
precisely to the ovule. Professor Tetsuya Higashiyama and 4 Vacuole dynamics in zygotes revealed with a powerful Dr. Minako Ueda, Professor Tetsuya Higashiyama and their team
his international colleagues have succeeded in analyzing
live imaging system: The importance of vacuole have discovered that the movement of vacuoles is involved in
for the first time, the crystal structure of LURE (key) bound
migration towards healthy plant development the asymmetry of plants fertilized eggs. As a result of observing
to its receptor protein PRK6 (pollen receptor-like kinase 6;
the movement of a vacuole in a fertilized egg in real time, the
lock). This unique binding scheme between LURE and PRK6
research team observed that when fertilization occurs the vacuole
appears to be involved in the precise control mechanism
rapidly dehydrates and becomes smaller and the vacuole moves
for the direction of pollen tube growth. Further elucidation
in a specific direction while dynamically changing its shape.
of this key and lock mechanism may lead to applications in
Moreover, if this mechanism is lost, not only can the zygotes
generating useful hybrid plant species.
no be divided asymmetrically, but the final shape of the plant
References: becomes abnormal; therefore, the importance of the dynamic
"Structural basis for receptor recognition of pollen tube attraction peptides" movement of the vacuole has become clear. This discovery is
by Xiaoxiao Zhang, Weijia Liu, Takuya T. Nagae, Hidenori Takeuchi, Heqiao expected to help clarify the mechanism of plant formation in the
Crystal structure of LURE bound to its receptor protein PRK6 (in Arabidopsis Zhang, Zhifu Han, Tetsuya Higashiyama and Jijie Chai, Nat. Commun. 2017, 8, future.
thaliana) 1331. DOI: 10.1038/s41467-017-01323-8
Vacuole and nucleus in References:
Arabidopsis zygotes. "Polar vacuolar distribution is essential for accurate asymmetric division
The wild type (left) of Arabidopsis zygotes" by Yusuke Kimata, Takehide Kato, Takumi Higaki,
properly polarized the
zygote, but a vacuole Daisuke Kurihara, Tomomi Yamada, Shoji Segami, Miyo Terao Morita,
mutant (right) failed and Masayoshi Maeshima, Seiichiro Hasezawa, Tetsuya Higashiyama,
thus formed a more Masao Tasaka and Minako Ueda, PNAS 2019, 116, 2338. DOI: 10.1073/
symmetric zygote. pnas.1814160116
18 195 Body clocks of animals and plants 6 Animal behavior and seasonality
1 Casein kinase 1 family regulates PRR5 and TOC1 in Using small molecules, an international team led by Dr. Norihito 1 Bossy rooster takes the lead vocal of cock-a-doodle- From ancient times, people have been aware of the rooster's
the Arabidopsis circadian clock Nakamichi and Professor Toshinori Kinoshita have revealed the doo: Social ranking in roosters affects order of crowing "cock-a-doodle-doo" that marks the break of dawn, but has
mechanism of Arabidopsis circadian clock. Organisms have anyone wondered who crows first? Professor Takashi Yoshimura
acquired a genetically integrated circadian clock to adapt to day- and his group have revealed that there is actually a systematic
night and seasonal changes. However, the mechanism of the rule based on social ranking that determines the order of crowing
circadian clock of land plants was not deciphered until now, due in roosters. They have also found that a rooster's circadian clock
to presence of a large number of paralogous genes from whole- is involved in their crowing at dawn.
genome duplication processes during evolution. The research
group has proved that multiple members of the casein kinase I References:
"The highest-ranking rooster has priority to announce the break of dawn"
(CK1) family is involved in Arabidopsis circadian clock, by using
by Tsuyoshi Shimmura, Shosei Ohashi, and Takashi Yoshimura, Sci. Rep.
a molecular probe of the small molecule that lengthens period
2015, 5, 11683. DOI: 10.1038/srep11683
of the circadian clock. In addition, substrate proteins of CK1 for “Circadian clock determines the timing of rooster crowing” by Tsuyoshi
period lengthening was identified. Given that plant circadian Shimmura and Takashi Yoshimura, Curr. Biol. 2013, 23, R231. DOI:
clock controls many physiological processes including flowering 10.1016/j.cub.2013.02.015
time regulation, further discovery of molecules modulating
circadian clock has profound implication of plant improvement,
which is important as one of our adaptation strategies to global
environmental change. 2 Shining light on the 100-year mystery of birds sensing Professor Takashi Yoshimura and his group have identified for the
References: spring for offspring first time, a key photoreceptor cell deep inside the brain of birds,
"Casein kinase 1 family regulates PRR5 and TOC1 in the Arabidopsis such as quails, which takes the role of eyes in humans by directly
circadian clock" by Takahiro N Uehara, Yoshiyuki Mizutani, Keiko Kuwata,
responding to light and regulates breeding activity according to
Tsuyoshi Hirota, Ayato Sato, Junya Mizoi, Saori Takao, Hiromi Matsuo,
seasonal changes. The study is expected to contribute to the
Takamasa Suzuki, Shogo Ito, Ami N Saito, Taeko Nishiwaki-Ohkawa,
Kazuka Yamaguchi-Shinozaki, Takashi Yoshimura, Steve Kay, Kenichiro
improvement of production of animals as well as deepen our
Itami, Toshinori Kinoshita, Junichiro Yamaguchi, Norihito Nakamichi, understanding on the evolution of eyes and photoreceptors.
PNAS 2019, 116, 11528. DOI: 10.1073/pnas.1903357116
References:
"Intrinsic photosensitivity of a deep brain photoreceptor" by Yusuke
Nakane, Tsuyoshi Shimmura, Hideki Abe and Takashi Yoshimura, Curr.
2 Discover new compound that changes the speed of Our biological circadian clock regulates various daily rhythms, Biol. 2014, 24, R596. DOI: 10.1016/j.cub.2014.05.038
the body clock: Suppresing the grwoth of cultured acute such as sleep/wake rhythm, body temperature, and metabolism.
myeloid leukemia cells Disruption of the circadian rhythm is linked with sleep disorders,
cancer and other diseases. The groups led by Dr. Tsuyoshi
Hirota and Professor Kenichiro Itami have successfully identified 3 One hormone, two roles: Sugars differentiate Using mice, Professor Takashi Yoshimura and his group have
GO289, which greatly lengthened circadian period. Found using a seasonality and metabolism discovered the mechanism on how a single hormone manages
cell-based phenotypic screen, the new compound is a potent and to trigger two different functions, i.e. seasonal sensing and
selective inhibitor of casein kinase 2 (CK2). Furthermore, GO289 metabolism, without any cross activity. Their studies uncovered
exhibited cell type–dependent inhibition of cancer cell growth that the elegant strategy of organisms, where tissue-specific
correlated with cellular clock function. This research open doors glycosylation and subsequent immune recognition is used to
to molecule-based solutions for circadian-related diseases. impart two distinctive functions on a single hormone.
References:
"Cell-based screen identifies a new potent and highly selective CK2
inhibitor for modulation of circadian rhythms and cancer cell growth" by
Tsuyoshi Oshima, Yoshimi Niwa, Keiko Kuwata, Ashutosh Srivastava,
References:
"Tissue-specific post-translational modification allows functional targeting
Tomoko Hyoda, Yoshiki Tsuchiya, Megumi Kumagai, Masato Tsuyuguchi,
of thyrotropin" by Keisuke Ikegami, Xiao-Hui Liao, Yuta Hoshino, Hiroko
Teruya Tamaru, Akiko Sugiyama, Natsuko Ono, Norjin Zolboot, Yoshiki
Ono, Wataru Ota, Yuka Ito, Taeko Nishiwaki-Ohkawa, Chihiro Sato,
Aikawa, Shunsuke Oishi, Atsushi Nonami, Fumio Arai, Shinya Hagihara,
Ken Kitajima, Masayuki Iigo, Yasufumi Shigeyoshi, Masanobu Yamada,
Junichiro Yamaguchi, Florence Tama, Yuya Kunisaki, Kazuhiro Yagita,
Yoshiharu Murata, Samuel Refetoff, Takashi Yoshimura, Cell Rep. 2014, 9,
Masaaki Ikeda, Takayoshi Kinoshita, Steve A. Kay, Kenichiro Itami,
801. DOI: http://dx.doi.org/10.1016/j.celrep.2014.10.006
Tsuyoshi Hirota, Science Advances, 2019, 5, eaau9060, DOI: 10.1126/
sciadv.aau9060
3 Revisiting existing drugs finds molecules that control Through drug repurposing, a team of researchers led by
4 Discovery of dynamic seasonal changes in color Professor Takashi Yoshimura and his group have discovered
body clocks: Discovery of an anti-aging supplement that Professor Takashi Yoshimura has discovered compounds that perception: The small fish "medaka" shows large that Japanese medaka fish show a difference in color perception
reduces jet lag in mice can either shorten or lengthen the circadian rhythm in human differences in color perception in summer and winter according to the season. Previous studies have also reported that
cells. They identified that DHEA (dehydroepiandrosterone), one human color perception changes according to the season. This
of the most abundant hormones in humans, also known as a phenomenon of seasonal change in color perception is therefore
common anti-aging supplement demonstrated period shortening not limited to medaka and may be a phenomenon widely
in cells and phase shifting activities in vivo. When it was fed to preserved in various animals.
mice, jet lag symptoms were significantly reduced.
Further screening of known bioactive compounds may lead to the
discovery of other effective compounds that can treat circadian
rhythm disorders.
References: References:
"Identification of circadian clock modulators from existing drugs" by "Dynamic plasticity in phototransduction regulates seasonal changes
T. Katherine Tamai, Yusuke Nakane, Wataru Ota, Akane Kobayashi, in color perception" by Tsuyoshi Shimmura, Tomoya Nakayama, Ai
Masateru Ishiguro, Naoya Kadofusa, Keisuke Ikegami, Kazuhiro Yagita, Shinomiya, Shoji Fukamachi, Masaki Yasugi, Eiji Watanabe, Takayuki
Molecules for entrainment of central and peripheral circadian clocks may Yasufumi Shigeyoshi, Masaki Sudo, Taeko Nishiwaki-Ohkawa, Ayato Shimo, Takumi Senga, Toshiya Nishimura, Minoru Tanaka, Yasuhiro
lead to the future drugs for circadian rhythms disorders and symptoms Sato, and Takashi Yoshimura, EMBO Mol. Med. 2018, 10, e8724. DOI: Kamei, Kiyoshi Naruse and Takashi Yoshimura, Nat. Commun. 2017, 8,
such as jet lag. 10.15252/emmm.201708724 412. DOI: 10.1038/s41467-017-00432-8
20 217 Molecules for live cell imaging 8 Organic synthesis and catalysis
1 Taking a deep look: a near infrared fluorescent dye A team of researchers from ITbM (Professor Shigehiro 1 At last: beautiful, consistent carbon belts Chemists have tried to synthesize carbon nanobelts for more
for long term bioimaging: Promising photostable tool for Yamaguchi, Dr. Masayasu Taki, etc.) and RIKEN and Ehime Synthesis of a carbon nanobelt with potential applications than 60 years, but none have succeeded until now. Professor
single molecule tracking, in vivo deep tissue imaging, and University have succeeded in developing a photostable in nanotechnology Kenichiro Itami and his group have reported the first total
multicolor imaging fluorescent dye that allows long term bioimaging of living cells in synthesis of a carbon nanobelt. Carbon nanobelts are expected
the near infrared region. In conventional fluorescence imaging to serve as a useful template for building carbon nanotubes and
of biological samples using visible light, it is difficult to observe would open a field of nanocarbon science.
deep blood vessels and organs due to cellular dysfunction,
light irradiation, and increased noise due to autofluorescence.
The joint research team succeeded in developing an extremely References:
"Synthesis of a Carbon Nanobelt" by Guillaume Povie, Yasutomo Segawa,
chemically- and photo-stable near-infrared fluorescence dye, Taishi Nishihara, Yuhei Miyauchi, Kenichiro Itami, Science 2017, 356, 172.
PREX 710, by the incorporation of a phosphine oxide moiety to DOI: 10.1126/science.aam8158
a rhodamine dye. This new labeling agent is useful for long-term
single molecule and deep imaging of blood vessels in the brain
because it has a site that can bind to biomolecules. This work has
future application to life sciences and medical research. 2 "Zipping-up" rings to make nanographenes: A fast and Professor Kenichiro Itami and his group have now developed a
efficient method for graphene nanoribbon synthesis facile route to form nanographenes in a controlled fashion. This
simple and powerful method for nanographene synthesis could
help generate a range of novel optoelectronic materials, such as
References: organic electroluminescent displays and solar cells.
"A Highly Photostable Near‐Infrared Labeling Agent Based on a Phospha‐
rhodamine for Long‐Term and Deep Imaging" by Marek Grzybowski,
Masayasu Taki, Kieko Senda, Yoshikatsu Sato, Tetsuro Ariyoshi, Yasushi
Okada, Ryosuke Kawakami, Takeshi Imamura, and Shigehiro Yamaguchi, References:
Angew. Chem. Int. Ed. 2018, 57, 10137. DOI: 10.1002/anie.201804731 "Synthesis of partially and fully fused polyaromatics by annulative
chlorophenylene dimerization" by Yoshito Koga, Takeshi Kaneda, Yutaro
Saito, Kei Murakami, and Kenichiro Itami, Science 2018, 359, 435. DOI:
10.1126/science.aap9801
2 Super-photostable fluorescent labeling agent for Drs. Masayasu Taki, Yoshikatsu Sato (Live Imaging Center), 3 Rapid synthesis towards optically active Professor Takashi Ooi and his group have developed a new
super-resolution microscopy: A powerful tool for 3D and Professors Shigehiro Yamaguchi, Tetsuya Higashiyama and their α-aminocarbonyl therapeutics: New catalytic asymmetric reaction to directly install amines into carbonyl compounds
multicolor STED imaging of cellular ultrastructure groups have developed a super-photostable fluorescent dye, reaction directly installs amines into carbonyl compounds using their unique phase-transfer catalyst. This unprecedented
PhoxBright 430 (PB430), to visualize cellular ultrastructure by method leads to the rapid formation of optically active (chiral)
super resolution microscopy. The exceptional photostability of this α-aminocarbonyls, which are structural moieties found in many
new dye enables continuous STED imaging. Together with its biologically active compounds and in therapeutics, such as anti-
ability to fluorescently label proteins, PB430 can be used in the malarial and anti-HIV agents.
3D construction and multicolor imaging of biological structures.
The unique properties of PB430 make it a powerful tool to reveal References:
"A Modular Strategy for the Direct Catalytic Asymmetric α-Amination
the structures and functions of cells, and has the potential to be of Carbonyl Compounds" by Kohsuke Ohmatsu, Yuichiro Ando,
applied for prolonged visualization of the movement of organelles Tsubasa Nakashima, Takashi Ooi, Chem 2016, 1, 802. DOI: 10.1016/
and molecules within cells. j.chempr.2016.10.012
References:
"Super-Photostable Phosphole-Based Dye for Multiple-Acquisition
4 Efficient synthesis of triarylmethanes: Sequential Dr. Masakazu Nambo and Professor Cathleen Crudden have
Stimulated Emission Depletion Imaging" by Chenguang Wang, Masayasu
Taki, Yoshikatsu Sato, Aiko Fukazawa, Tetsuya Higashiyama, and incorporation of aryl rings by palladium catalysts synthesized unsymmetric triarylmethanes, which a privileged
Shigehiro Yamaguchi, J. Am. Chem. Soc. 2017, 139, 10374. DOI: structure, from methyl phenyl sulfone as an inexpensive and
10.1021/jacs.7b04418 readily available template. The three aryl groups were installed
3D imaging of the cytoskeleton with PB430 through two sequential palladium-catalyzed C–H arylation
reactions, followed by an arylative desulfonation reaction.
References:
"Modular Synthesis of Triarylmethanes through Palladium-Catalyzed
Sequential Arylation of Methyl Phenyl Sulfone" by Masakazu Nambo,
Cathleen M. Crudden, Angew. Chem. Int. Ed. 2013, 53, 742. DOI:
10.1002/anie.201307019
5 "Pick 'n' Mix" chemistry to grow cultures of bioactive Professor Jeffrey Bode and his group have developed a new
molecules method, "synthetic fermentation", to build large libraries of
bioactive peptide molecules, which can be used directly for
biological assays. This is achieved by simply mixing a small
number of building blocks (amino acid derivatives) in water.
References:
"Synthetic fermentation of bioactive non-ribosomal peptides without
organisms, enzymes or reagents" by Yi-Lin Huang and Jeffrey W. Bode,
Nature Chem. 2014, 6, 877. DOI: 10.1038/nchem.2048
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