Bacteria Yield Spider Silk

WINTER 2020

SHOWCASING THE BEST OF JAPAN’S PREMIER RESEARCH ORGANIZATION • www.riken.jp/en/

HUMAN HIBERNATION? Mouse studies hint at possibilities

CURRENT THINKING Low-energy skyrmion control

MULTIPLE DESIGNER SCLEROSIS Bacteria pair worsen symptoms THREADS ONE Bacteria yield spider silk DIRECTION How magnets manipulate sound ▲ Problematic pair Multiple sclerosis (MS) is caused by MS-microglia cells (red) that damage the myelin sheath of neuron axons (blue). In an article published in Nature in September 2020, researchers from the RIKEN Center for Integrative Medical Sciences (IMS) looked at how two gut bacteria working together worsened MS.

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publication is a selection research in this publication or Getty / selvanegra Images© TABLE OF CONTENTS

Editorial Research 3 Supporting serendipity 10 highlights in a post-COVID-19 world 10 Mystery of particle generation in proton collisions deepened People 11 Unlocking the key to cell identity and health 4 Searching for the secrets of spin 12 How the brain sorts smells p.12 Xiuzhen Yu 13 Blood cell mutations linked Team Leader to leukemias are inevitable as we age Helping regenerative ideas flourish 14 Finding materials that buck the trend Cody Kime Special Postdoctoral 15 Detecting the death of Researcher decrepit mitochondria

16 Starved fish are hungry p.15 for victory

Briefs 6 Celebrating 30 years of RIKEN-RAL

Plans for a new RIKEN quantum computing center

RIKEN and JAXA collaborate on real-time rainfall forecasts

Yokohama campus holds its annual open day online

Global Summit of Research Institute Leaders

Secondary and tertiary students participate in Fugaku Challenge

RIKEN Image/Video Competition winners

WINTER 2020 1 TABLE OF CONTENTS

Research COVER STORY 17 highlights Perspectives 26 Hijacking hibernation: In the last few years, scientists have 17 Pulses that are short on time, but high on energy been able to clarify the energy- saving mechanisms at work in hibernation, culminating in two COVER STORY important papers published in 18 Tag team worsens June 2020. But what does this FEATURES multiple sclerosis mean for human hibernation? symptoms

19 Skyrmions without the frustration

COVER STORY Feature COVER STORY 20 Gently nudging A one-way street for sound waves: A new way for sound skyrmions along 29 waves to interact with magnetic film could lead to 80% more 21 Supernova had a missing directional control companion star

COVER STORY 22 Modified bacteria weave spider silk

23 Plant defence provides opening for parasite

24 Mystery of oversized placentas solved

25 Light induces a different kind of sound wave

A ONE-WAYInfographic STREET 32 How best to map tissue cells: The most powerful of 13 single-cell RNA sequencing methods tested by an international group for their ability to map the cells FORin complexSOUND tissues is RIKEN's Quartz-Seq2. WAVES We look at the results of a study designed to help large-scale A new way collaborativefor sound tissue waves mapping to projects, such as the Human Cell Atlas, as they seek to interact withstandardize magnetic sequencing film could methods. p.24 lead to 80% more directional control © 2020 RIKEN

2 WINTER 2020 RIKEN RESEARCH 29 EDITORIAL

Supporting serendipity in a post-COVID-19 world

Yuko Harayama Executive Director

n early October we hosted the Global Summit encounter new ideas beyond the sphere of the scien- of Research Institute Leaders, a roundtable on tific community to which we belong. WINTER 2020

SHOWCASING THE BEST OF JAPAN’S PREMIER RESEARCH ORGANIZATION • www.riken.jp/en/ academic management that is held annually as When thinking about this missing piece, I con- part of the Science and Technology in Society template diversity, which is part of my responsibility IForum. This year, of course, was special, as the at RIKEN. We often think of diversity in terms summit was held as an online event. of gender or ethnicity, but I think that we should

HUMAN HIBERNATION? We are learning a great deal about living and think of it in a broader way, in terms of ways of Mouse studies hint at possibilities

CURRENT working in a world with COVID-19. It’s a bit ironic thinking, feeling and acting. In this new era, we will THINKING Low-energy skyrmion control

MULTIPLE DESIGNER that while we have realized that cooperation is more be required to act more intentionally to compensate SCLEROSIS Bacteria pair worsen symptoms THREADS important than ever, we have also found that collab- for the lack of spaces for serendipity and casual ONE Bacteria yield spider silk DIRECTION How magnets oration has become more complex. interactions between different types of people and manipulate sound We have found many tools to help us work scientific communities. I hope that we can think of together, which is encouraging. However, I think ways to promote informal communication among COVER STORY: A RIKEN team have there is something missing. I feel that one important people both within, and among, different institutes. produced very strong element of meetings and events is the chance for I believe that talking among ourselves will give us and lightweight spider informal communication. These discussions can fresh ideas on how to move forward and to design silk using photosynthetic not only be a wonderful source of inspiration, but new spaces for serendipity. bacteria. Page 22 can also lead to new research collaborations, even We would love to hear any ideas from our © 2020 Greg Seymour / years later. It’s a chance to run into people and to partners both inside and outside Japan on this and Getty Images; maintain friendships. However, our new working other issues related to our work in this new era. EyeEm / Getty Images style makes those kinds of contact more difficult, and conversations tend to be much more focused. This can make it hard to experience ‘serendipity’, which is important to science, as it allows us to

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WINTER 2020 3 PEOPLE

structures that correlate with novel physical properties. It has allowed us to Searching for the prove that when external stimuli trigger a structural transition in crystals of topological spin textures between tetragonal secrets of spin and hexagonal lattices, there is an effect on these topological spin-textures; they transform between the meron and Xiuzhen Yu skyrmion spin states. Team Leader Electronic States Microscopy Research Team, How did you join RIKEN? RIKEN Center for Emergent Matter Science The director of the Center for Emergent Matter Science, Tokura Yoshinori, is a pioneer of condensed matter physics and I had always wanted to join Describe your role at RIKEN. Please briefly describe your Tokura’s RIKEN group. Luckily, I I lead a team focused on microscopic current research. became part of the Tokura FIRST phenomena, including tiny magnetic We are using atomic resolution Lorentz program as a postdoctoral fellow in vortices called skyrmions transmission electron microscopy to 2010. The FIRST program funded young and antiskyrmions. directly observe emergent phenomena PhD candidates to train with world- These phenomena in strongly correlated electron leading researchers to encourage them are found in systems, including the realization of to direct research and development substances in different topological spin textures. with practical applications. their solid state, also known My research is important to as condensed society because… matter materials. The ability to manipulate nanom- My team was the eter-scale spin textures is a key to the development of spintron- first to observe skyrmions in ics (next-generation electronic a helimagnet and recently devices that consume very little power). We believe that observed its antiparticle in these spin textures could real time. be used to transmit data and logic in a similar way to the What do you think has been bits in standard the most interesting discovery in computing. The your field in the last few years? secret to the low Although researchers have been power consump- hypothesizing about skyrmions for tion of spin several decades, they were only textures is that it experimentally proven for the first can be stimulated time in 2009. After that finding, using minimal there was a boom in worldwide electric charge. skyrmion research. In 2010, my team was the first to observe What excites skyrmions in a helimagnet using you about improved Lorentz transmission electron your current microscopy under external magnetic research? fields. We also recently observed its Our Lorentz antiparticle, the antiskyrmion, in real transmission time. These findings pave the way for electron micro- more work toward real-world applica- scope allows us tions. We are now developing a 3D to study crystal imaging technique to directly visualize structures and minute topological spin textures for

4 RIKEN RESEARCH PEOPLE

bioinformatics and analytical technolo- Helping regenerative gies developed at RIKEN. What do you wish you had known before you came to Japan? ideas flourish I wish I had known more about the quality of day-to-day life in Japan. Living in Japan has its pros and cons, but it Cody Kime feels very safe and has the highest level Special Postdoctoral Researcher/Cell Reprogramming Team Lead of convenience (transportation, food, Laboratory for Retinal Regeneration, school, finance, etc.) that I have ever RIKEN Center for Biosystems Dynamics Research seen. I have a family, so those qualities are incredibly valuable. Also, the quality of raw and prepared foods here is so high that nearly everything is really a Describe your role at RIKEN. and grow in the uterus of a fertile treat to eat. ■ I have assembled a team focused mouse mother was, by far, the most life- on creating new cell reprogramming changing moment for me at RIKEN. I was Careers at RIKEN systems to practically address retinal shaking and crying as the importance of For further disease and vision loss. I am also a young that fact became real to me. information, visit our Careers page: investigator in the Organoid Project Website: www. at the RIKEN Center for Biosystems How has being at RIKEN helped riken.jp/en/careers Dynamics Research (BDR). I specialize in your research? E-mail: [email protected] the emerging field of synthetic embryo- RIKEN, Dr Takahashi and the Retina genesis; we are working to generate Lab have supported my research with early embryo-like structures and cells funds and enthusiasm for more than five from reprogrammed stem cells. years. The Retina Lab’s doctors provide critical medical insight and incredibly How did you become interested in rare retina transplant skills. I also your field? performed my most critical I fell in love with cell reprogramming embryo transplant tests when I was asked to review Shinya with Dr Hiroshi Kiyonari Yamanaka’s seminal 2006 and 2007 of BDR’s Lab for Animal papers on iPS cells while at university in Resources and the United States. Genetic Engineering (LARGE). Recently, How and when did you join RIKEN? I started working I joined Masayo Takahashi’s Lab for with the Retinal Regeneration (the Retina Lab) Takasato and in 2015 as an International Program Kuraku labs Associate while enrolled for medical at the BDR science at the Kyoto University Graduate to expand School of Medicine. Dr Takahashi is doing my skills in some of the world’s most cutting-edge single cell RNA work on retinal regeneration with iPS sequencing cells in collaboration with Dr Yamanaka. through advanced I wanted to join RIKEN to work in the Next Generation developmental biology environment from Sequencing/bioinfor- which my field originated, so I proposed matics. In Yokohama, a new cell reprogramming method to Piero Carninci, Erik treat retinal disease, and the Retina Lab Arner and their associ- agreed to develop it with me. ates at the RIKEN Center for Integrative Medical What has been your most Sciences have been key memorable experience at RIKEN? collaborators, helping The moment that I had concrete evidence me to train and experi-

WINTER 2020 5 BRIEFS

Isao Watanabe, now a Senior Research Scientist in RIKEN's Meson Science Laboratory, at the RIKEN-RAL Muon Facility in 1994.

Celebrating 30 years of RIKEN-RAL

The RIKEN-RAL Muon Facility is one of of users from Japan and the UK continue As it is 30 years since the partnership the largest and longest-standing international research partnership work. began, and there are 30 days in September, science collaborations at the ISIS Neutron September marked 30 years since the the RIKEN-RAL Muon Facility released one and Muon Source, which is located at the first agreement for the facility was signed video message of congratulations and one Rutherford Appleton Laboratory in Oxford- in 1990. The facility produced first muons highlight each day during September 2020. shire in the United Kingdom. The facility, in 1994, and was officially inaugurated in “We've created and sustained a very strong used for fundamental and applied studies April 1995. Since then it has produced more international partnership that has produced on or using muons, was owned and operated than 500 papers, had researchers from over excellent science over three decades,” says by RIKEN until 2018, after which the 90 Japanese institutions come to use it, and Phillip King, Director, RIKEN Facility Office operators of the base facility took over. stimulated collaborations with a further at RAL. “It is an achievement that RIKEN Since then the Oxfordshire-based facility 40 institutions around the world including and ISIS can be rightly proud of." and RIKEN have been collaborating on a agreements between RIKEN and universities https://www.isis.stfc.ac.uk/Pages/30-years- significant refurbishment, while a number in Indonesia, Malaysia and South Korea. RIKEN-ISIS.aspx © 2020 RIKEN

6 RIKEN RESEARCH BRIEFS

RIKEN to launch new quantum computing center

By 2021, RIKEN will establish a quantum technology research center, tentatively dubbed the ‘Quantum Computer Center’ as part of the Japanese government’s ‘Quantum Technology Innovation Strategy’. At the new center, RIKEN will bring together researchers who study quantum electronics and quantum computers, currently at the RIKEN Center for Emergent Matter Science (CEMS). With this organizational change, RIKEN will further strengthen the work on the research and development of A JAXA supercomputer combined with nowcasting is producing highly accurate rain predictions up to five quantum computers and related basic days in advance. science, basic technology, hardware and software. A newly established ‘Planning Office for the Quantum Computing Center’ RIKEN and JAXA collaborate is working to develop a management system based on an integrated approach on real-time rainfall forecasts that takes advantage of RIKEN’s strengths, as well as promoting coopera- Researchers from RIKEN, Chiba Univer- precipitation data called GSMaP. This tion with other research and develop- sity, the University of Tokyo and the Japan new numerical weather prediction system, ment agencies and private companies. Aerospace Exploration Agency (JAXA) have running on the JAXA Supercomputer System The office is also working to develop used a combination of satellite data and Generation 2 (JSS2) allows forecasts up to an international platform for quantum supercomputer simulations to offer five-day five days in advance. computing research that carries out rainfall forecasts over the Internet covering The latest advance was to combine the everything from basic research to tech- the globe. The new system combines a variety forecasts made on the supercomputer with nology validation, open innovation, of techniques, particularly precipitation now- the nowcasting, to create a sophisticated intellectual property management, and casting and numerical weather prediction, to system that relies heavily on nowcasting human resource development with come up with predictions that are accurate for the first few hours and then gradually top-class researchers and engineers from on a variety of time scales. shifting to the supercomputer simulations for Japan and overseas. For the project, which began in 2013, the forecasts further in the future. group of researchers began experimenting According to Takemasa Miyoshi of the with ways to make more accurate rainfall RIKEN Center for Computational Science forecasts. They began by developing a (R-CCS), who has been leading the project, system—using data assimilation—to incor- “Climate change is leading to changes in porate observational data, from weather weather patterns, and it is very important to satellites, into a type of forecasting called create more accurate forecasts of rainfall to nowcasting—where the most recent data is mitigate damage. We hope that our research used to predict what will happen in several using satellite data will be helpful in prevent- hours based on a motion tracking technique, ing losses from heavy rain and drought, par- without relying on sophisticated computer ticularly in the areas where we have limited models. Forecasts of this system for up to 12 observing capability.” hours were made available starting in 2017. https://www.riken.jp/en/news_pubs/ The next step of the group’s research was news/2020/20200820_2 to develop a sophisticated numerical weather Forecasts are available from RIKEN at: prediction model, known as NICAM, and https://weather.riken.jp/index_en.html or Yasunobu Nakamura, Director of the Planning a data assimilation method, called LETKF, from JAXA at https://sharaku.eorc.jaxa.jp/

WINTER 2020 7 BRIEFS

Global Summit of Research Institute Leaders

Multilateral collaboration during the COVID-19 pandemic was the focus of this year’s Ninth Global Summit of Research Institute Leaders, held in conjunction with the STS Forum's Annual Meeting. Twenty- six national research institutes leaders from around the world attended online. Among the issues raised was the fact that the global pandemic represents a 'moment for science' and there is a need to mobilize scientific resources on a global scale both to combat the current epidemic and to prepare for future ones. Participants stressed the need to maintain transparency and trust in Senior Scientist Oleg Gusev from the Laboratory for Transcriptome Technology carried out a live science, and to have flexible funding and other discussion on the mechanisms of the sleeping chironomid. mechanisms to ensure that research organiza- tions can swiftly set up multilateral projects and share resources to combat crises. It was resolved the institutes would explore new modes of multilateral collaboration, enabling Yokohama campus holds use of human and other resources most effec- tively in this unique situation. its annual open day online RIKEN and the National Institute of Advanced Industrial Science and Technol- Once a year in the early fall, RIKEN’s The Yokohama Campus is home to ogy (AIST) co-hosted the meeting which was Yokohama Campus opens its doors to many foreign researchers. Allen Yi-Lun co-chaired by RIKEN's President, Hiroshi members of the public with tours, seminars, Tsai, a Special Postdoctoral Researcher in Matsumoto, and President Matthias Kleiner of hands-on experiences and other special the Dormancy and Adaptation Research the Leibniz Association. programs designed to increase knowledge Unit at the RIKEN Center for Sustainable of the life sciences and the research work Resource Science gave a seminar entitled done onsite. Activities are developed, 'A Canadian researcher in the Far East and organized and run by RIKEN Yokohama the globalization of academia', while Oleg and Yokohama City University Tsurumi Gusev, a Senior Scientist in the Laboratory Secondary and Campus, which are situated on the same site. for Transcriptome Technology at the The 2020 Open Day was held online for RIKEN Center for Integrative Medical tertiary students the first time in the interest of preventing the Sciences, carried out a live program on the participate in spread of COVID-19. Twenty-three different mechanisms of the sleeping chironomid. programs took place, with some taking The year 2020 also marked the 20th Fugaku Challenge advantage of the unique opportunity to try anniversary of the RIKEN Yokohama something new, such as a virtual reality lab Campus. In commemoration of this Due to the coronavirus, the final round tour with a 360-degree camera or live experi- milestone, Kazuo Shinozaki, Special of the annual Supercomputing Contest ment broadcasts via YouTube. In a normal Advisor and Group Director at RIKEN’s (SuperCon), a programming competition for year, RIKEN Yokohama and Yokohama Center for Sustainable Resource Science, high school and technical college students, City University Tsurumi Campus Open Day gave a lecture on life science development was cancelled. Instead an event called activities bring some 3,000 visitors, mostly over the last two decades. A special retro- the ‘Fugaku Challenge’ was held between from the local community in Yokohama and spective website also allows participants September 13 to 20, 2020. At this event, 16 Kawasaki. The online format attracted more to look at the Yokohama Campus and its teams from throughout Japan were able to than 3,000 viewers from around Japan, since research results over the past 20 years. stretch their skills and use the new super- participants did not need to be physically https://www.riken.jp/pr/ computer Fugaku to complete a challenge, present to take part. news/2020/20200907_3 with every participant receiving a prize.

8 RIKEN RESEARCH BRIEFS

STEREO PROJECTION OF HIGH RESOLUTION CLOUD SIMULATION Toshiki Matsushima, RIKEN R-CCS

CHRISTMAS LIGHTS Thomas Chater, RIKEN CBS RIKEN IMAGE/VIDEO COMPETITION WINNERS RIKEN held its first institute-wide image and video competition to find the best images/videos of RIKEN’s campuses, facilities and research. Over 90 entries were received from 13 centers/divisions from throughout RIKEN. These entries will be featured in future promotional material.

WINTER 2020 9 RESEARCH HIGHLIGHTS

NUCLEAR PHYSICS Mystery of particle generation in proton collisions deepened A consensus among nuclear physicists is challenged by measurements of collisions between protons

team of RIKEN researchers than the other three fundamental A has challenged the previous forces. One avenue for exploring consensus regarding particle these important challenges has generation in measurements involved an attribute of protons of collisions between protons, called spin. The spin of protons shedding light on the cascade of can be artificially aligned by a particles produced when particles process called polarization. from outer space enter the Earth’s Accelerator experiments atmosphere1. in the 1970s revealed that The Earth is constantly being subatomic particles known as bombarded by high-energy pions generated near the front particles from outer space. These of collisions involving polarized so-called cosmic rays are mostly protons were not evenly distrib- hydrogen nuclei (that is, protons), uted but were strongly skewed but a small percentage of them are in the left–right plane. Experi- nuclei of heavier elements. They ments using even more energetic collide with nuclei in the upper protons showed that this left– atmosphere and produce cascades right asymmetry persisted even of particles that fall towards the at higher energies. A consensus Earth. Since most high-energy emerged that this asymmetry particles originate outside our was caused by direct interactions Solar System, such showers among the quarks and gluons in provide a valuable window on the protons. extreme astrophysical phenomena Now, a team led by Yuji Goto such as supernova. at the RIKEN Nishina Center for Accelerator-Based Science An artist’s impression of cosmic rays. High-energy particles and radiation from a star in deep space generate a cascade of subatomic particles when they hit the (RNC) has found evidence that atmosphere. Measurements of collisions between protons by RIKEN researchers “This result challenges this consensus. By shed new light on these cascades of particles looking at gamma rays generated necessitates a by pion decays at the very forward “This result necessitates a reex- reexamination of region of the collision, they found amination of previous theoretical Reference previous theoretical that the left–right asymmetry interpretations.” 1. Kim, M. H., Adriani, O., in neutral pions persists even “We plan to continue our work Berti, E., Bonechi, L., D’Alessandro, R., Goto, Y., interpretations.” in that very narrow area, where to understand the mechanism Hong, B., Itow, Y., Kasahara, quarks and gluons do not directly that generates the left–right K., Lee, J. H. et al. interact. asymmetry,” says Minho Kim, Transverse single-spin However, it is difficult to study “We found that the asymmetry also at RNC. “This is sure to asymmetry for very forward how particles are created, since continues to exist at a very give us insights into cosmic-ray neutral pion production in polarized p + p collisions the force that binds protons in the narrow angle from right in showers and thus help us to at √s = 510 GeV. Physical nucleus and that bind quarks and front of the collision, and in fact understand phenomena that take Review Letters 124, 252501 gluons into protons—the strong increases as the angle moves place in the extreme environment (2020).

nuclear force—is much stronger away from zero,” says Goto. of the Universe.” LIBRARY PHOTO GARLICK/SCIENCE MARK ©

10 RIKEN RESEARCH RESEARCH HIGHLIGHTS

TRANSCRIPTOMICS Unlocking the key to cell identity and health RNA plays critical roles in defining cell types and regulating cell functions

wo RIKEN-led studies have Tidentified a core regulatory network that governs cell types in different vertebrate species and uncovered the role that RNA plays in regulating cell identity and function1,2. Understanding RNA (the transcriptome) is crucial for advancing biology because although the cells in our bodies share the same DNA, their diversity depends on their RNA make-up. Thus, understanding how RNA is expressed is critical for grasping how each cell type establishes its distinc- tive function, morphology and behavior by activating specific transcriptional programs. RIKEN is spearheading research in this area through the FANTOM Consortium, which was established two decades ago. Using an automated screening platform (shown in this photograph) and CAGE, a RIKEN-developed technology based on The first study1 compared next-generation sequencing, RIKEN researchers have profiled the transcriptome of human cells. transcriptome data from matching primary cell types Medical Sciences (IMS). “On the investigating RNA biology in in human, mouse, rat, dog and other hand, genes that primarily detail and its potential application Reference chicken. The team used CAGE, act in communication between to enhancing human health.” 1. Alam, T., Agrawal, S., a RIKEN-developed technol- cells had diverged and were being The team found that more than Severin, J., Young, ogy based on next-generation used differently in different 25% of long non-coding RNAs R. S., Andersson, R., Arner, E., Hasegawa, A., sequencing, to profile the species.” affected cell growth and mor- Lizio, M., Ramilowski, transcriptome. Although the The second study2 looked at phology, as well as cell migration, J. A., Abugessaisa, transcriptome differed markedly human long non-coding RNAs, which is important in cancer. I. et al. Comparative between species for the same cell whose function is poorly under- Surprisingly, targeting different transcriptomics of primary cells in vertebrates. type, a core regulatory network stood. Using an automated isoforms (variants) of the same Genome Research 30, that defined each cell type was robotics system, the research- long non-coding RNA led to 951−961 (2020). common between species. In ers suppressed nearly 300 long profoundly different cellular and general, the genes encoding non-coding RNAs in human molecular phenotypes, giving 2. Ramilowski, J. A., Yip, products involved in RNA fibroblast cells. They then used rise to the enticing conjecture C. W., Agrawal, S., biology in the cell nucleus were live cell imaging with CAGE to that each isoform produced by a Chang, J.-C., Ciani, Y., Kulakovskiy, I. V., Mendez, activated consistently in the same observe how the cells responded cell might have its own specific M., Ooi, J. L. C., Ouyang, cell type regardless of species. at cellular and molecular levels. regulatory function. J. F., Parkinson, N. et al. “We identified genes acting “This allowed us to perform “We’re excited to see that long Functional annotation of within the nucleus whose usage a functional analysis of long non-coding RNAs, often consid- human long noncoding RNAs via molecular was conserved for hundreds of non-coding RNAs at an unprec- ered ‘junk’ when discovered some phenotyping. Genome millions of years of evolution,” edented level,” says Jordan 15 years ago, are often proven Research 30, 1060−1072 says Michiel de Hoon of the Ramilowski of the IMS. “It to be functional,” says Piero (2020).

WINTER 2020 11 RESEARCH HIGHLIGHTS

OLFACTION How the brain sorts smells A fly study uncovers how the brain classifies mixtures of odors into broad categories

hree RIKEN neuroscientists T have discovered how the fruit fly brain classifies smells into categories1. This finding explains how different individuals perceive varying odors similarly. Animals use their sense of smell to recognize food sources, predators, potential mates and family. Despite odors generally being a mixture of Colored scanning electron micrograph of the head of a fruit fly. RIKEN neuroscientists have discovered how the fruit fly brain volatile molecules, animals do classifies smells into categories. not recognize each molecule one by one, but rather the explains Hokto Kazama of the calcium released by activated generate unitary representations entire mixture as a single RIKEN Center for Brain Science. neurons. They found that for individual odors as well as smell. However, it is not well “Previous studies had only clusters of neurons in the groups and mixtures of odors,” understood how the brain recorded from less than 5% of mushroom body responded says Kazama. “Because the basic generates common categories of them, which was not enough for selectively to individual odors, wiring pattern of the olfactory odors from these mixtures. our purposes.” They overcame mixtures, or groups of odors. circuit is highly conserved across The common fruit fly, whose this problem by developing an In contrast, neurons in the phyla, we believe that the type of olfactory system has been very algorithm that automatically antennal lobe responded much computations we have discovered well mapped on the neuron level, locates and tracks all the cells less selectively. These results here may also be found in other can recognize and generalize over an hour of recording. imply that the mushroom more complex animals, such odors. In the fly brain, odor body integrates input from as humans. We are curious information travels from the the antennal lobe and creates to know if these odor object primary olfactory center, Different flies had distinct odor representations. representations remain stable called the antennal lobe, to the similar neural The trio was able to reproduce or flexibly change over time secondary center, called the their experimental results as animals experience various mushroom body. expressions of using a mathematical model of odors in their environment.” The team investigated unitary odors in neural information processing. differences between these two From this, they discovered that brain regions in the sensory their mushroom different flies had similar neural Reference pathway, which required bodies expressions of unitary odors 1. Endo, K., Tsuchimoto, Y. simultaneously measuring the in their mushroom bodies, & Kazama, H. Synthesis responses from many more which can explain why different of conserved odor object representations neurons than has been done The researchers presented flies individuals recognize odors in a random, divergent- previously. “Characterizing the with 15 different odors, both similarly. convergent network. activity of all 2,000 cells of the individually and in mixtures, “The most surprising finding Neuron 108, 367–381 mushroom body at once was and recorded their neuronal was that the same computation (2020). the biggest technical hurdle,” responses by imaging the in the olfactory circuit can © POWER AND SYRED/SCIENCE PHOTO LIBRARY

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Colored scanning electron micrograph (SEM) of hematopoietic stem cells, which are destined to become various kinds of blood cells, including immune cells such as T cells and B cells. Genetic mutations in hematopoietic stem cells vary between Japan and Europe, RIKEN researchers have found.

CANCER EPIDEMIOLOGY strongly suggest that chromo- The researchers found somal alterations in hematopoi- genetic components related to etic clones are an inevitable event the risk of having clonal HSC Blood cell mutations in the very old,” says Terao. mutations. The likelihood of a Comparisons with data from person having one of the critical linked to leukemias are the UK Biobank revealed that mutations now or in the future more than 80% of mutations in can be estimated by looking for inevitable as we age T-cell lineages occurred in the these variations in their DNA. Japanese population, whereas “Not everyone with these Links between blood cell mutations and leukemias more than 90% of B-cell lineage mutations gets cancer,” empha- have been clarified in a comparison study mutations occurred in the sizes Terao. “A simple blood European sample. These data test that you can get at any are consistent with reported regular health checkup will be ifferences in blood cell be identified from their DNA. For cases of leukemia—T-cell able to identify people at risk of D mutations between example, all T cells derived from a leukemia occurs 10 times more leukemia by checking for clonal Japanese and European popula- particular HSC are clones of each often in Japanese people than HSC mutations. A DNA test tions can explain why the rates of other. If the HSC had a mutation, in Europeans, whereas chronic based on the blood sample can different kinds of leukemias vary all the T cells in that lineage will lymphocytic leukemia, a B-cell- also identify those at high risk between Europe and Japan, a possess that mutation, but T cells related leukemia, is five times of developing the critical HSC RIKEN-led study has found1. from different HSCs won’t have it. more prevalent in Europeans. mutations in the future.” Our blood cells are continu- These types of clonal This doesn’t imply that ously being renewed from a stock mutations have been studied mutations selectively occurred of blood stem cells in the bone in European populations, but in different genes depending on Reference marrow. These stem cells, called Chikashi Terao and his team at the population. The data only 1. Terao, C., Suzuki, A., Momozawa, Y., Akiyama, hematopoietic stem cells (HSCs), the RIKEN Center for Integra- included clonal mutations that M., Ishigaki, K., Yamamoto, produce progenitor cells that tive Medical Sciences suspected survived and replicated enough K., Matsuda, K., Murakami, in turn give rise to the many they might get different results in to be detectable. “We can infer Y., McCarroll, S. A., Kubo, different kinds of blood cells, their older Japanese population that the advantage of a particular M. et al. Chromosomal including immune cells such as of almost 180,000 individuals. chromosomal mutation differs alterations among age- related haematopoietic T cells and B cells. They found that more than 35% depending on the genetic and clones in Japan. Nature Blood cells that come from the of people over 90 years old had environmental context,” 584, 130–135 (2020).

WINTER 2020 13 RESEARCH HIGHLIGHTS Machine learning can predict the properties of new materials, thereby saving scientists a lot of time synthesizing them in the laboratory. RIKEN researchers have developed an algorithm that can discover special materials that go against the trend set by other materials.

MATERIALS DISCOVERY results. BLOX then uses the model to predict the properties of a new set of materials. From Finding materials that buck the trend these new materials, BLOX identifies the one that deviates A new algorithm can roam the material landscape looking for materials that the most from the overall dis- offer the best of both worlds tribution. The properties of that material are determined by experiment or calculations and machine-learning solar cells, where it is desired to eXploration), that can locate out- then used to update the machine A algorithm that can predict maximize both the voltage and of-trend materials. learning model, and the cycle is the compositions of trend- current, notes Kei Terayama, The team demonstrated the repeated. defying new materials has been who was at the RIKEN Center algorithm’s power by using it Importantly, unlike many developed by RIKEN chemists1. for Advanced Intelligence Project to identify eight out-of-trend previous algorithms, BLOX It will be useful for finding and is now at Yokohama City molecules with a high degree imposes no restrictions on the materials for applications where University. “There’s a trade-off of photoactivity from a drug- range of material structures there is a trade-off between two between voltage and current: discovery database. The proper- and compositions that can be or more desirable properties. a material that exhibits a high ties of these molecules exhibited explored. It can thus range Artificial intelligence has great voltage will have a low current, good agreement with those far and wide in its search for potential to help scientists find whereas one with a high current predicted by the algorithm. “We outlying materials. new materials with desirable will have a low voltage.” had concerns about the accuracy The team has made BLOX properties. A machine-learning Material scientists thus fre- of the calculation but were freely available online (http:// algorithm that has been trained quently want to find ‘out-of- delighted to see that the calcula- github.com/tsudalab/BLOX). with the compositions and trend’ materials that buck the tion was correct,” says Terayama. properties of known materials usual trade-off. But unfortu- “This shows the potential of can predict the properties of nately conventional machine- computation-driven materials Reference unknown materials, saving learning algorithms fare much development.” 1. Terayama, K., Sumita, M., Tamura, R., Payne, D. T., much time in the lab. better at spotting trends than BLOX uses machine learning Chahal, M. K., Ishihara, S. & But discovering new materials discovering materials that go to generate a prediction model Tsuda, K. Pushing property for applications can be tricky against them. for key material properties. It limits in materials discovery because there is often a trade-off Now, Terayama and his does this by combining data for via boundless objective- between two or more material co-workers have developed a materials randomly selected free exploration. Chemical Science 11, 5959–5968 properties. One example is machine-learning algorithm, from a materials database with (2020). organic materials for organic BLOX (BoundLess Objective free experimental or calculation Monty© Rakusen/Getty

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MITOPHAGY Detecting the death of decrepit mitochondria A probe that works in both live and fixed cells can give key insights into neurodegenerative disorders

versatile probe that can A detect with pinpoint accuracy the programmed destruction of defective mitochondria—the powerhouses of cells—has been developed by RIKEN researchers1. They used it to show that damaged mitochondria in dopamine-producing neurons fail to be destroyed in mice with a condition resem- bling Parkinson’s disease. Mitochondria are organelles that generate most of the chemical energy our cells need to function. But when cells are stressed, mitochondria can malfunction and produce highly reactive oxygen radicals, which damage cells. Thus, cells routinely weed out and destroy defective mitochondria by assigning them to lysosomes, which function as the waste- disposal system of cells, breaking down unwanted components. If this selective elimination of Colored transmission electron micrograph of a single mitochondrion in a human pancreas cell. RIKEN researchers have dysfunctional mitochondria— developed a fluorescent probe that can detect the programmed death of defective mitochondria in the lysosomes. known as mitophagy—fails, it can lead to various diseases. by them. Thus, by monitoring dopamine failed to eliminate neurodegenerative disorders There is thus much interest in the color of the probe’s fluo- defective mitochondria, but other involve mitophagy, our probe monitoring mitophagy in cells. rescence, the researchers could neurons that did not produce can contribute to their study,” Fluorescent probes have detect when a mitochondrion dopamine did. Since Parkinson’s says Miyawaki. “Furthermore, been developed that can detect had entered a lysosome. Unlike disease is characterized by a diseases in other organs involve mitophagy. But some can only be their previous mitophagy probe, dopamine deficiency in the brain, oxidative stress and hence used in living cells, while others the new probe is sensitive to the this suggests that the inability of mitophagy. We’re currently are vulnerable to destructive degrading enzymes in lysosomes dopamine-producing neurons to using our probe to look at heart processes that do not involve and acidity, so it works even in perform mitophagy could be a disease.” lysosomes. fixed cells where lysosomes are major factor in the disease. Now, Atsushi Miyawaki of the no longer acidic. By collaborating with research- RIKEN Center for Brain Science The team used the probe ers from the pharmaceutical Reference and co-workers have developed to investigate Parkinson’s company Takeda, Miyawaki’s 1. Katayama, H., Hama, H., Nagasawa, K., Kurokawa, a new fluorescent probe that can disease—a neurodegenerative team identified a compound H., Sugiyama, M., Ando, be used in both living and fixed disease that causes shaking, that can induce the destruction R., Funata, M., Yoshida, N., cells and is highlighted specifi- muscle stiffness and progressive of damaged mitochondria. Such Homma, M., Nishimura, cally in lysosomes. difficulties with movement. compounds could help to treat T. et al. Visualizing and Their probe contains two Using a mouse model of Parkinson’s disease in the future. modulating mitophagy for therapeutic studies of parts: one that can withstand Parkinson’s disease, the research- The probe is promising for neurodegeneration. Cell the enzymes in the lysosome ers found that neurons that advancing research into other 181, 1176–1187.e16 (2020).

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SOCIAL NEUROSCIENCE Starved fish are hungry for victory Hunger activates a pathway in the brain of a zebrafish that makes the fish less likely to give up in a fight against another zebrafish

epriving a zebrafish of food for six explains Nakajo. “And since winners D days boosts its chances of winning of fights secure more resources such as a fight against a well-fed fish because food, it makes sense that starved fish try starvation activates a certain pathway harder to win fights.” in its brain, neuroscientists at RIKEN Hunger may cause similar effects in have shown1. This finding could well people too. “The habenula–interpe- have implications for other animals and duncular pathway is evolutionary humans since the neural pathway is conserved from fish to humans,” conserved across species. says Nakajo. “So we think that Social animals, including fish, cats and similar functions are conserved primates, often fight to establish the social even in humans.” hierarchy of a group and hence who gets One surprise was that hunger first pick of limited resources such as food activated the winner pathway and mates. Neuroscientists are interested in the habenula via a neuro- in uncovering how networks in the brain peptide called orexin. Orexin regulate such social behaviors. Zebrafish is well known for its role in make good subjects for these studies regulating sleep and appetite, because they display well-defined fighting but it had not previously been behaviors. implicated with social behaviors If asked to bet on the outcome of a such as fighting. It was also fight between a well-fed zebrafish and the first time that orexin has one that hadn’t eaten in six days, most been shown to regulate the people would probably put their money expression of specific genes, on the well-nourished fish. But a study by Nakajo says. a RIKEN-led team has found that in 75% The team is now intending of fights, the hungry zebrafish emerges as to investigate the molecular the victor. mechanisms behind this In an earlier study, the team had dis- hunger-activated pathway. covered that a zebrafish would tend to win fights when a specific pathway originating in a brain structure called the Reference 1. Nakajo, H., Chou, habenula was activated, whereas it would M.-Y., Kinoshita, have a propensity to lose fights if another M., Appelbaum, L., pathway in the same region was activated. Shimazaki, H., Tsuboi, Now, Haruna Nakajo and Hitoshi T. & Okamoto, H. Okamoto of the RIKEN Center for Brain Hunger potentiates the habenular winner Science, together with their co-workers, pathway for social have shown that starving zebrafish conflict by orexin- activate the ‘winner pathway’ in the promoted biased habenula, making them less likely to give alternative splicing of the AMPA receptor up during a contest with another fish. gene. Cell Reports 31, There is logic to this finding. “Hungry 107790 (2020). fish are more motivated to obtain food,”

Colored 3D reconstructed micro-computed tomography scan of the head of a zebrafish. RIKEN researchers have shown that hunger activates a neural pathway in the habenula that makes a fish less likely to give up in a conflict with another fish.

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ATTOSECOND SCIENCE Pulses that are short on time, but high on energy Ultrashort, energetic pulses can now be generated by combining three highly controlled pulses

way to reliably produce A x-ray pulses that are both incredibly short and have high energies has been demonstrated by physicists at RIKEN1. This will allow researchers to investigate ultrashort phenomena that involve multiple photons. It is hard to appreciate how short an attosecond is. Each second is made up of a quin- tillion (1018) attoseconds; the equivalent number of seconds would be more than twice the current age of the Universe. Light can travel from the Earth to the Moon in about 1.25 seconds, but it covers a mere 0.3 nanometers in an attosecond. When scientists produced laser pulses on the timescale of several hundred attoseconds in 2001, they opened up new vistas to researchers. In particular, it became possible to probe and control the motion of electrons In a fluorescence microscopy experiment (shown here), white light is split into its component colors. RIKEN scientists in molecules. have done the reverse—they have combined three laser pulses of different wavelengths using a high-energy waveform Pulse durations have dropped synthesizer to generate high-energy pulses in the attosecond regime. to a few tens of attoseconds today, but one limitation is that techniques. Moreover, despite To realize the stability they convinced our method will pave the pulses have low energies. being an attosecond pulse, its needed, the team developed the way to realize nonlinear atto- Producing more-energetic peak power exceeds a gigawatt,” a stabilized, high-energy second-science experiments in attosecond pulses will allow says Takahashi. amplifier for driving their the near future,” says Takahashi. researchers to explore nonlinear The team produced these synthesizer. This high-energy “This will certainly catalyze phenomena that involve two or pulses by combining, or synthe- laser amplifier stretches a pulse research on ultrafast phenomena more photons. sizing, three pulses with wave- in duration, amplifies it, and and nonlinear optics.” Now, Eiji Takahashi of the lengths ranging from red light then compresses it with actively RIKEN Center for Advanced to infrared light. Importantly, stabilizing carrier-envelope Photonics and his co-workers they were able to achieve precise phases. “The development of Reference have produced high-energy control over the timing and shape this amplifier was one of the 1. Xue, B., Tamaru, Y., Fu, Y., Yuan, H., Lan, P., Mücke, O. pulses in the attosecond regime. of these pulses, allowing the team key achievements in this study,” D., Suda, A., Midorikawa, “To the best of our knowledge, to both optimize and accurately says Takahashi. K. & Takahashi, E. J. Fully the combination of the reproduce them. The researchers The team anticipates that their stabilized multi-TW optical 240-nanojoule energy and then used the combined pulse method will accelerate research waveform synthesizer: 170-attosecond duration of our to produce an attosecond pulse in the attosecond regime. In Toward gigawatt isolated attosecond pulses. Science isolated attosecond pulses rep- using a nonlinear process known particular, it will be useful for Advances 6, eaay2802 resents a new record for studies as high-order harmonic genera- probing electrons using atto- (2020).

© K H FUNG/SCIENCE PHOTO LIBRARY; ANDREW BROOKES, NATIONAL PHYSICAL LABORATORY/SCIENCE PHOTO LIBRARY PHOTO LABORATORY/SCIENCE PHYSICAL NATIONAL BROOKES, ANDREW LIBRARY; PHOTO FUNG/SCIENCE H K © using synthesizers or other tion in argon gas. second spectroscopy. “We’re

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AUTOIMMUNITY Tag team worsens multiple sclerosis symptoms Two bacteria working in tandem intensify symptoms in mouse model of multiple sclerosis

he discovery by RIKEN T researchers that two gut bacteria worsen symptoms in mice with a multiple-sclerosis- like condition could lead to new treatments for the debilitating disorder1. Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin membrane that protects nerve cells in the brain and spinal cord. This damage causes symptoms such as numbness, weak muscles, tremors, and the inability to walk. Gut microorganisms are known to affect the symptoms of multiple sclerosis, but just how bacteria in the intestines affect myelin in the brain and spinal cord has been a mystery. Now, a team led by Hiroshi Ohno at the RIKEN Center for Integrative Medical Sciences (IMS) has investigated this con- nection using mice that experi- Stained spinal-cord sections from control (left) and ampicillin-treated (right) mice models of multiple sclerosis. The ampicillin- ence similar demyelination of the treated sample shows reduced demyelination. spinal cord due to autoimmune attacks by T cells that produce a which bacteria in the small another bacterium was cross- treatments for multiple sclerosis, certain cytokine. intestine activate MOG-specific reacting with MOG-specific T further studies on human The antibiotic ampicillin both T cells, which then attack myelin. cells, mimicking the location on microbes and autoreactive T cells reduced demyelination in these Because only ampicillin reduced MOG that the T cells recognize. are needed since humans have mice (see image) and prevented symptoms in the model mice, Shotgun genome sequencing different gut microbes and T the activation of a particular type they looked for gut microbes revealed that a protein expressed cell-binding locations on myelin of T cell that attacks a protein that were almost completely by the bacterium Lactobacil- than mice. called myelin oligodendrocyte deleted only in ampicillin- lus reuteri resembles a region glycoprotein (MOG), which treated mice. Just one bacterium of MOG, and when tested, it helps myelin stick to neurons. fitted the bill—a strain called weakly activated MOG-specific Reference When the researchers took OTU002. The team found that T cells. Mice co-colonized with 1. Miyauchi, E., Kim, S.-W., immune cells from the small mice lacking all bacteria except L. reuteri and OTU002 had more Suda, W., Kawasumi, M., Onawa, S., Taguchi- intestines and other regions OTU002 had more severe severe symptoms than OTU002- Atarashi, N., Morita, H., and measured their cytokine symptoms than germ-free mice. only mice and just as severe Taylor, T. D., Hattori, production in the presence of “But there was a problem,” symptoms as the original model M. & Ohno, H. Gut MOG, cytokine production was says Eiji Miyauchi, also of IMS. mice, indicating that the results microorganisms act together to exacerbate reduced only by ampicillin and “Symptoms in the OTU002-only are devastating when these two inflammation in spinal only when the T cells came from mice were not as bad as those in bacteria work together. cords. Nature 585, 102–106 the small intestine. the regular model mice.” While these results provide (2020).

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RIKEN physicists have created an array of skyrmions (green swirls) in a material that is both centrosymmetric and lacks a property called geometrical frustration. The blue spheres are conduction electrons.

SKYRMIONS room temperature, which will be a huge boost for their use in applications. “We’re now looking Skyrmions without the frustration for a new system that has a magnetic ordering temperature Tiny magnetic swirls can form in a broader range of materials than have been at close to room temperature or used in previous experiments even above,” says Nguyen. After a fortuitous encounter at a conference last year, the team restriction on the kind of special class of materials whose They created a square array of has been collaborating with A materials that can host crystal structures lacked a skyrmions that are less than 2 theorists at the University of nanoscale magnetic whirlpools center of symmetry. Last year, nanometers in diameter—the Tokyo to uncover the mechanism known as skyrmions has been a RIKEN-led team succeeded smallest skyrmions created to that allows skyrmions to be lifted by experimentalists at in creating them in a material date in a single material—in created without geometric frus- RIKEN1. This will significantly that had a center of symmetry, the centrosymmetric tetragonal tration. “We were very surprised

expand the range of the materials increasing the range of materials magnet GdRu2Si2. to learn that they are working skyrmions can be created in, that could host skyrmions. They This demonstration expands on the problem and that their making them even more attrac- were able to do this because their the range of materials that theoretical results agree very well tive for use in low-power data- material possessed a property skyrmions can be hosted in with our experimental results,” storage devices. known as geometric frustration, even more. “Rare-earth inter- Nguyen notes. First discovered a little over a where the geometry of a material metallic compounds are a very decade ago, skyrmions are highly prevents the system from broad class of materials,” says promising for application in adopting the lowest possible Nguyen. “Our finding means Reference low-power, high-density storage energy state at low temperatures. that skyrmions can be created in 1. Khanh, N. D., Nakajima, and transfer of data. They are Now, Shinichiro Seki and many compounds—they’re no T., Yu, X., Gao, S., Shibata, K., Hirschberger, M., attracting increasing interest, Nguyen Duy Khanh of the longer restricted to a very limited Yamasaki, Y., Sagayama, and there are predictions that the RIKEN Center for Emergent class of material.” H., Nakao, H., Peng, first skyrmion-based commer- Matter Science and their co- Since geometric frustra- L. et al. Nanometric cial devices will start appearing workers have gone a step further tion kicks in only at very low square skyrmion lattice in a centrosymmetric in about ten years. and shown that skyrmions temperatures, the finding that tetragonal magnet. Nature However, until recently, can be created even in cen- it is not needed for generating Nanotechnology 15, skyrmions had been observed trosymmetric materials that skyrmions raises the possibil- 444–449 (2020).

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SKYRMIONS Gently nudging skyrmions along A low electric current is all that is needed to manipulate tiny magnetic whirlpools

n a first step that could lead to I the development of much more energy-efficient memory devices, a RIKEN team has manipulated and tracked the movement of individual skyrmions—tiny magnetic vortices—using electric currents that are about a 1,000 times weaker than those used in conventional hard disk drives1. Skyrmions are both tiny— generally tens of nanometers in diameter—and robust. It is thus possible to cram multitudes of them into a minuscule area, while it is difficult to accidentally erase them. Both properties make skyrmions highly attractive as building blocks for next-generation computer memories and logic devices. However, their small size causes skyrmions to bunch together in crystalline lattices (see image), which require hefty electric currents to move around. Skyrmions tend to group together and form lattices, which are difficult to move. RIKEN researchers have succeeded in These large currents would make developing a method that can move them using electrical currents. devices less energy efficient as well as generate undesirable heat. has now succeeded in using the manipulation of skyrmions The team is now planning to Researchers have been trying very small electric currents since their magnetic moments enhance their device to make to isolate individual skyrmions to isolate and manipulate followed the helical patterns. it more amenable to real-life because they are much easier to individual skyrmions that were By adding a square notch to applications. “By developing manipulate, but this has proved 80 nanometers in diameter. the film, the researchers were a bilayer system that can host difficult to achieve until now. “We have demonstrated that able to confine a spin current combined skyrmions, we plan it is possible to manipulate and at a point near a corner of the to further improve the device to track individual skyrmions notch. They then experimented enable it to be used in practical “We hope that and its crystal using a relatively with applying pulses of electric applications,” says Yu. this will help the low electric current,” says Yu. current in one direction and “We hope that this will help the then the opposite direction while development of development of more energy- monitoring the results with a Reference efficient racetrack memory Lorentz transmission electron 1. Yu, X. Z., Morikawa, D., more energy- Nakajima, K., Shibata, K., as well as neuromorphic microscope. This allowed Yu efficient racetrack Kanazawa, N., Arima, T., computing.” and her team to locate a point Nagaosa, N. & Tokura, memory” The researchers used a thin on the film where they could Y. Motion tracking of film of a magnetic material isolate individual skyrmions. 80-nm-size skyrmions whose magnetic domains They recorded the skyrmion upon directional current injections. Science A team led by Xiuzhen were organized in a spiral movement using an emergent Advances 6, eaaz9744 Yu of the RIKEN Center for arrangement. This unusual phenomenon known as the (2020).

Emergent Matter Science magnetic structure facilitated topological Hall effect. Matter Science Emergent for RIKEN Center 2020 ©

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The Cassiopeia A supernova remnant as observed by NASA’s Chandra X-ray Observatory. Calculations by RIKEN based on Chandra data indicate that the progenitor star had a companion, which has yet to be observed.

CORE-COLLAPSE SUPERNOVAE Supernova had a missing companion star A fresh analysis of x-ray data suggests that one of the best known supernovae had a companion star

he massive star that exploded have theoretical scenarios, but we metallicity of Cassiopeia A for found to date. T to form the supernova would like to confirm them by the first time. They did this by “The reason it hasn’t been known as Cassiopeia A most observations.” combining data from the 13 observed may be because it is a likely had a companion star that An important parameter in observations of the supernova by compact, faint object such as a has yet to be spotted, a spectro- studying the evolution of stars is the Chandra X-ray Observatory black hole, a neutron star or a scopic analysis by RIKEN astro- the ratio of heavier elements to over the past 18 years to find the white dwarf,” says Sato. “This physicists suggests1. This will the lightest element, hydrogen—a ratio of the elements manganese finding thus provides a new provide fresh impetus to efforts ratio known as the metallicity. to chromium at the time of the direction for understanding to locate the companion. Shortly after the Big Bang, explosion. From this ratio, they the origin of Cassiopeia A. We Supernovae are among the there were only three elements: estimated that the initial metal- hope it will lead to a signifi- most violent events in the hydrogen, helium and lithium. licity of Cassiopeia A was lower cant advance in understanding Universe. They occur when a But with each succeeding genera- than that of the Sun. the mechanism of supernova massive star exhausts its supply tion of stars, heavier elements Cassiopeia A is known as a explosions.” of fuel and its core collapses have become increasingly stripped envelope supernova under the huge gravitational pull abundant. because its outer layer of of the star. The starting metallicity of a hydrogen has been stripped Reference While theories have been put star is an important factor in away. But the low initial metal- 1. Sato, T., Yoshida, T., Umeda, H., Nagataki, S., forward to explain the processes determining its fate. “The initial licity implies that the stellar Ono, M., Maeda, K., Hirai, involved, they are yet to be cor- metallicity affects the way a star wind would have been too weak R., Hughes, J. P., Williams, roborated by observations. “The dies,” says Sato. “So it is very to strip the hydrogen layer B. J. & Maeda, Y. A subsolar explosion mechanisms of massive important to investigate the away. The only explanation that metallicity progenitor for stars are a long-standing problem initial metallicity to understand remains is that it was removed Cassiopeia A, the remnant of a type IIb supernova. in astrophysics,” notes Toshiki how a star exploded.” by a companion star—a surpris- The Astrophysical Journal Sato of the RIKEN High Energy Now, Sato and his co-workers ing finding since no indication 893, 49 (2020).

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SPIDER SILK Modified bacteria weave spider silk Genetically modifying a bacterium that lives in seawater causes it to produce high-quality spider silk

new era in which breed large numbers of spiders. A photosynthetic biofactories Consequently, attempts have stably output spider silk could be been made to produce artificial realized as a result of a RIKEN spider silk in a variety of species. team producing spider silk from A team led by Keiji Numata of photosynthetic bacteria1. the CSRS focused on the marine Spiders produce amazingly photosynthetic bacterium strong and lightweight threads Rhodovulum sulfidophilum—an called draglines, which are made ideal bacterium for establishing from silk proteins. In addition a sustainable biofactory because to being tough and lightweight, it grows in seawater, requires silks from arthropod species are carbon dioxide and nitrogen in biodegradable and biocompatible, the atmosphere, and uses solar making them attractive for energy, all of which are abundant various applications. and inexhaustible. The researchers genetically engineered the bacterium to The fibers produced produce the protein MaSp1, the main component of the Nephila in the bacteria were spider dragline, which is thought very similar to those to be important for the strength of spider silk. By optimizing the produced naturally gene sequence that was inserted by spiders into the bacterium’s genome, the researchers were able to maximize the amount of silk By genetically engineering bacteria, RIKEN researchers have succeeded in getting it to produce MaSp1, the main component of the dragline of the Nephila “Spider silk has the potential produced. spider (shown here). to be used in the manufacture of They also found that a simple high-performance and durable recipe—artificial seawater, are now working to mass Our results will help provide materials such as tear-resistant bicarbonate salt, nitrogen gas, produce spider-silk dragline feasible solutions for energy, clothing, automobile parts yeast extract, and irradiation proteins at higher molecular water and food crises, solid- and aerospace components,” with near-infrared light— weights in our photosynthetic waste problems and global says Choon Pin Foong of the allowed R. sulfidophilum to grow system,” Numata says. “The warming.” RIKEN Center for Sustainable well and produce the silk protein photosynthetic microbial Resource Science (CSRS). “Its efficiently. Further observations cell factories, which produce biocompatibility makes it safe for confirmed that the surface and bio-based and biodegradable Reference use in biomedical applications internal structures of the fibers materials via a carbon neutral 1. Foong, C. P., Higuchi- Takeuchi, M., Malay, A. D., such as drug-delivery systems, produced in the bacteria were bioprocess, could help us in Oktaviani, N. A., Thagun, implant devices and scaffolds for very similar to those produced accomplishing some of the C. & Numata, K. A marine tissue engineering.” naturally by spiders. Sustainable Development Goals photosynthetic microbial But getting enough of the “Our current study shows adopted by the United Nations, cell factory as a platform for spider silk production. protein is difficult because a the initial proof of concept such as Goal #12 ‘Responsible Communications Biology 3, single spider produces a small for producing spider silk in Production and Consumption’ 357 (2020). amount and it is difficult to photosynthetic bacteria. We and Goal #13 ‘Climate Action’. Science Sustainable Resource for RIKEN Center 2020 ©

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PARASITIC PLANTS Plant defence provides opening for parasite A parasitic plant exploits a molecular mechanism that plants use to keep bacteria out

ew strategies for combating Nthe beautiful but devastating crop parasite witchweed (Striga) could come from a link RIKEN researchers have discovered between the parasite and the defense responses in plants1. Annual global losses due to Striga parasites attacking crops such as maize, sugarcane and sorghum amount to well over a billion US dollars. All varieties of the parasite sense DMBQ, which belongs to a class of aromatic compounds widely found in plants known as quinones. Striga then forms appendage-like organs that it uses to invade the host and siphon off water and nutrients. Ken Shirasu and his co-workers at the RIKEN Center for Sustainable Resource Science want to find ways to prevent crop losses from the parasite by developing treatments or Striga- resistant crops. This requires understanding the molecular A photograph of asiatic witchweed (Striga asiatica), a red-flowered parasitic plant. RIKEN researchers have discovered a link between the parasite and the defense responses in plants. events in the parasitic plant’s response to quinones. “We needed to answer a more basic the quinone activates the CARD1 signaling pathway. side effect of making crops question: why are quinones in protein. Satisfied that the CARD1 more susceptible to bacterial non-parasitic plants in the first The team tested whether protein is essential for immune- infection,” explains Shirasu. place?” says Shirasu. quinone signaling is related to related responses to quinones “Another approach could be to The researchers found that immune responses and found in non-parasitic plants, the create crops that do not produce the model plant Arabidopsis that the card1 mutants were more team investigated if quinone quinones, but can still initiate produced a calcium signal in easily infected by a common signaling in parasitic plants was the downstream responses response to quinones. When they bacterium than wild-type plants. related to a similar gene. They that provide protection from examined 50,000 mutagenized A typical immune response in found CARD1-like proteins in microbial infection, perhaps seedlings, they found 11 mutants plants is to close pores in their a model parasitic plant, which with treatment.” lacking this response. All 11 leaves to prevent pathogens from were expressed in the roots and mutants had mutations in the entering. Further analysis showed also involved in DMBQ-induced same gene, which the researchers that these stomatal pores failed to calcium increase. Reference 1. Laohavisit, A., Wakatake, dubbed cannot respond to close in the mutant plants because Understanding plant quinone T., Ishihama, N., Mulvey, DMBQ 1 (card1). the plants could not respond signaling should provide targets H., Takizawa, K., Suzuki, A genetic analysis showed that to quinones. This likely led to for combating parasitic plants T. & Shirasu, K. Quinone a non-parasitic plant sets off a the increased susceptibility to and rule out other targets. “Our perception in plants biological chain of events that infection. Pretreating plants with current research shows that if via leucine-rich repeat receptor-like kinases. involves responses to wounds and DMBQ increased resistance to we simply target quinones, it Nature 587, 92–97 (2020).

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SOMATIC CELL NUCLEAR TRANSFER Mystery of oversized placentas solved The birth rate of a cloning technique can be doubled by correcting for the absence of an epigenetic mark

ne reason a technique for fertili- O cloning animals often zation. results in oversized placentas, One and hence failed births, has reason been uncovered in mice by an for this all-RIKEN team1. This finding is that the will help improve the success placentas of the rate of the cloning method and artificially fertilized could also shed light on fertility embryos are often abnor- treatments for people. mally large, which frequently The cloning method known leads to developmental compli- A mouse embryo (left) produced by somatic cell nuclear transfer (SCNT) attached as somatic cell nuclear transfer cations. But even after 20 years to a normalized placenta (right). RIKEN researchers have discovered why SCNT produces such large placentas. (SCNT) made headlines in 1997 of research, the cause of this problem has remained a mystery. Now, Kimiko Inoue, Atsuo that SCNT placentas’ lack of beyond SCNT. “We’ve dem- When they corrected Ogura and their co-workers, genomic imprinting based on the onstrated that non-coding for this, they were all at the RIKEN BioResource epigenetic mark histone methyl- microRNA plays an essential Research Center, have discovered ation goes a long way to explain- role in the healthy develop- able to double the that the overexpression of the ing their abnormal size. ment of placentas,” says Inoue. birth rate. largest imprinted microRNA “DNA methylation is the main “I anticipate this will help us clusters in mice is one of the epigenetic mark that governs this understand placental abnormali- main reasons why SCNT often expression system,” says Inoue. ties and develop gene markers when Dolly the sheep became produces placentas that are too “However, imprinting specific for assisted reproductive tech- the first mammal cloned from an large. When they corrected for to the placenta is regulated by nologies for people.” adult cell. It involves swapping this, they were able to double the trimethylation at lysine 27 of the nucleus of an egg cell from birth rate. histone H3 and this represses the the mother with a nucleus from A process known as genomic expression of the mother’s gene.” Reference 1. Inoue, K., Ogonuki, N., a normal somatic cell from the imprinting guides the early Inoue wasn’t expecting to find Kamimura, S., Inoue, H., nuclear donor animal and then development of mammals by that the culprit was a microRNA Matoba, S., Hirose, M., placing the egg into the uterus switching certain genes on and that didn’t code for proteins. “I Honda, A., Miura, K., of a surrogate mother. SCNT is a off as the embryo and placenta was surprised to discover that a Hada, M., Hasegawa, A. et al. Loss of H3K27me3 powerful tool for basic research, develop and grow. This can lead non-protein-coding microRNA, imprinting in the Sfmbt2 medicine, agriculture and envi- to the expression of genes from and not a protein-coding gene, miRNA cluster causes ronmental science. only one parent, depending on was the main cause of the enlargement of cloned However, despite significant small molecules attached to the oversized placentas produced by mouse placentas. Nature progress, SCNT’s birth rate is genetic sequence called epige- SCNT,” she says. Communications 11, 2150 (2020). still well below that of natural netic marks. The team found The study has repercussions Center Research RIKEN BioResource 2020 ©

24 RIKEN RESEARCH RESEARCH HIGHLIGHTS

Most sound waves are longitudinal waves (bottom of image), but some are transverse (top of image) and cause the atoms or molecules of the material to oscillate perpendicular to their direction of travel. RIKEN researchers have succeeded in generating transverse sound waves in a thin flake of VTe₂.

PHOTOACOUSTIC WAVES Light induces a different kind of sound wave Ultrashort laser pulses induce unusual sound waves via a structural instability in a material

IKEN physicists have “This allows us to make novel laser pulses to induce a struc- microscopy was one of the most Rinitiated unusual sound functionality in very small tural instability, altering the important aspects of our study,” waves in a flake of VTe2 using devices.” crystal structure of the material says Nakamura. “It allowed us to ultrashort pulses of laser light Most sound waves compress and producing a transverse take electron microscopy videos and then created videos of their and expand the material along the sound wave. They were able to of the sound waves.” movement using electron micros- direction they travel in—these are detect this change in structure The researchers are excited copy1. This advance should help known as longitudinal waves. But from electron diffraction by the potential of their micro- engineers to achieve higher some sound waves are transverse measurements. scope. “It will allow us to evaluate precision control of heat flow and and cause the atoms or molecules Transverse waves promise quantitatively the amplitude of sound in nanodevices using light. of the material to oscillate per- to give engineers greater ver- acoustic waves by electron dif- In 1880, Alexander Graham pendicular to their direction of satility. “By utilizing this new fraction,” says Nakamura. “Also, Bell, of telephone fame, reported travel (see image). mechanism, it may be possible to our system can visualize magnetic that light can be converted into In previous experiments that control the direction of atomic structures and waves.” sound waves in some materials. used light to induce sound waves displacement in sound waves in Now, 140 years later, this effect in nanomaterials, the light heated the future,” says Nakamura. is generating a lot of interest the material, causing it to expand The team imaged the waves in Reference because it can be used to control in all directions and thereby the flake using a special electron 1. Nakamura, A., Shimojima, the flow of heat and sound in creating longitudinal sound microscope—one of only two T., Chiashi, Y., Kamitani, M., nanomaterials. waves. Now, Nakamura and his in Japan. This was no mean Sakai, H., Ishiwata, S., Li, H. & Ishizaka, K. Nanoscale “By utilizing this effect we co-workers have used a different feat because the flake was just imaging of unusual can manage heat and sound on mechanism to produce trans- 75 nanometers thick and the time photoacoustic waves in thin

a nanometer scale,” says Asuka verse sound waves in a thin flake resolution was on the order of flake VTe 2. Nano Letters −12 20, 4932–4938 (2020). Nakamura of the RIKEN Center of VTe 2. picoseconds (1 picosecond = 10

WINTER 2020 25 PERSPECTIVES HI JACK ING HIBERNATION In the last few years, scientists have been able to clarify the energy-saving mechanisms at work in hibernation, culminating in two important papers published in June 2020.

But what does this mean for human hibernation?

26 RIKEN RESEARCH © 2020 RIKEN H WINTER blood flow increases after months of inactivity. In In of inactivity. months after increases flow blood when cells their protect to melatonin use squirrels hibernating For example, science. for medical ities off. while year the throughout level cellular on the occur adjustments hibernation-related complex revealed have bears of hibernating transcriptomes on the away. Studies don’t lemurs waste the and maintained are activity, cell muscle as such essentials, that mean adjustments 90% by nearly plummets activity metabolic its and temperature body set its lowers lemur hollow, this atree into safely tucked While hibernate. to known are species lemur other three at least ayear, and months for seven up to state energy-saving this enters Madagascar, to native lemur dwarf fat-tailed the primate, Another Maybe. next? humans Are torpors. temporary go into only normally standing of the neurons and neuropeptides that might might that neuropeptides and neurons of the standing nucleus preoptic median smaller much the but in thought, previously as area, preoptic medial broader hypothalamus’ the in located not are hypothermia in seen temperature But hibernation still holds some exciting possibil exciting some holds still But hibernation the early 2000s, a University of Nebraska team team of Nebraska aUniversity 2000s, early the the key neurons that cause the sudden drop in body body in drop sudden the cause that neurons key the 2 temperature changes. The studies revealed that that revealed studies The changes. temperature , so long bouts of human hibernation are a little alittle are hibernation of human long bouts , so used this as inspiration for a treatment to reduce reduce to for atreatment inspiration as this used tissue damage when blood suddenly returns returns suddenly blood when damage tissue markers involved in the body’s response to skin skin to body’s response the in involved markers 2020 after trauma-related hemorrhagic shock. shock. hemorrhagic trauma-related after to a small flurry of studies on the genetic genetic on the of studies flurry asmall to After recent success in rats in success recent After Nebraska team is now looking at clinical at clinical now looking is team Nebraska such as rats and mice, the latter of which of which latter the mice, and rats as such non-hibernators in induce hibernation how to discovered recently have very However, we aren’t hibernators. umans model has been brewing since 2016 due since brewing been has model activation in the brain. This change to the the to change This brain. the in activation could of hibernation bouts Short trials.

previous model of thermoregulation of thermoregulation model previous also be helpful in limiting tissue damage damage tissue limiting in helpful be also both support modifications to the the to modifications support both in stroke victims or organ transplants. or organ victims stroke in state. an energy-saving, hibernation-like hibernation-like energy-saving, an understanding our when this to closer body temperatures in mice, inducing inducing mice, in temperatures body Two forward. leapt of hibernation 7,8,9 nerve that, when activated, lower set lower set activated, when that, nerve optic of end the the behind subsets neuron specific several have identified in published both studies, These studies, one of which I co-led, Ico-led, one of which studies, These On 11 June 2020, we took a step astep we took 2020, June 11 On . This greatly refined our under our refined greatly . This 1 . Complex physiological physiological Complex . 3 and pigs and Nature 4 , the the , 5,6 - - , began recording the metabolism of the genetically genetically of the metabolism the recording began dropped. temperature body their and still became 2017, mice in QRFP their express that neurons the exciting tried group However, his when active. very them responses—made adrenal and feeding to linked been has of mice—QFRP brains the into QFRP injecting that He observed drugs. marketed of all of half up to targets the are that carriers message of group diverse a receptors, G-protein-coupled of brain the in functions examining long been has Sakurai of Tsukuba. University at the group his and Sakurai, paper, on Takeshi our author responding cor the and expert by wakefulness neuropeptides of study long-time the in lie mice in state tion-like of hiberna activation successful of our origins The HIBERNATION? SYNTHETIC MEDICAL humans. ultimately and mammals, in control state of hibernation development the in result eventually could that something we have found that is hope the state, hibernation subsequent and activation artificial the achieve to mice our modified genetically neurons same of these activation duced drug-in after mice in states torpor shorter observing findings, our it echoed and States, United the in School Medical Harvard at the by researchers led hibernation states hibernation of reminiscent body-temperature, set-point lowered a and dormancy alonger achieve to we able were (QRFP) mice, in peptide RF-amide pyroglutamylated express that of neurons subset small the activating by that was excitement caused that study June of our aspect But the of food. alack to response in torpors adjustments. physiological more much sophisticated requires this but or more, by 90% use for energy longer, lowering temperature body set-point animal’s an reduce ments, environ extreme in living animals in seen often most benefits energy-saving for the of coldness afeeling enduring be may animals the and same, the remains temperature set-point animal’s torpor, the daily However, this use. in energy in a70% reduction as much as achieve to thought is which temperature, air ambient to closer temperature body lower their can animals some torpors, daily shorter afever. to clue In first our is humans in rise aone-degree even why That’s Fahrenheit). degrees (98.6 Celsius of 37degrees point aset around range body-temperature have anarrow mammals Most consumption. energy to key is Thermoregulation BY BODY HEAT BURDENED of hibernation. mechanism central the is which thermoregulation, in involved be Sakurai called me soon after, and my Kobe lab soon soon lab my Kobe and after, mesoon called Sakurai daily energy-conserving short go into can Mice 5 . The other study I mentioned was was Imentioned study other . The 10 . Deeper hibernation states, states, hibernation . Deeper 6 . While we we . While - - - - Center for Biosystems Regeneration, RIKEN forLaboratory Retinal Biology of Aging and forLaboratory Molecular Senior Scientist, GENSHIRO SUNAGAWA use in clinical settings. human hibernation for hopes to develop safe such as hibernation. He of natural phenomena biomedical applications of field the in a step inspired him to take Dausmann in 2004, primates by Kathrin of hibernating tropical discovery The 2001. sinceand anesthetist) clinician (pediatrician been working as a in mammals. He has hypometabolism active on focuses he where Regeneration since 2015, forLaboratory Retinal the in working been has Genshiro Sunagawa Research Dynamics © MediaProduction / Getty Images PERSPECTIVES 27

PERSPECTIVES

in human iPS cell-derived tissues. If we can do this without modifying the genes involved, the possibilities of using short-term dormancy for medicine becomes more real.

LONG HUMAN HIBERNATION In terms of longer hibernation states, things become more complex. The fat tissue of grizzly bears has been shown to be among the most affected by hibernation. A 2019 transcriptional analysis showed 900 differ- entially expressed genes in a hibernating grizzly’s adipose tissue compared to an active season. Hiber- nation was also characterized by reduced expression of genes associated with insulin signaling, muscle protein degradation, and urea production, and increased expression within muscle protein anabolic pathways. It’s thought that we contain the genes that make this possible, but activating these supporting processes in humans would likely be hugely complex. However, grizzly bears also become resistant to insulin during hibernation, but they don’t suffer from fluctuating blood sugar levels. Huge weight loss occurs as par for the course, but no bone loss or atrophied muscles have been observed. A human experiencing some of these conditions could easily end up with diabetes, obesity or worse. Will mimicking grizzly bear fat become a future treatment for diabetes? Is aging slowed by hibernation? Could we enter torpor for a few hours every night as part of a beauty or health regime? One theory suggests that deep med- itation is designed to replicate hibernation. Can we The researchers observed modified mice with a special G protein-coupled achieve a hibernation or torpor state using only the that QFRP-neuron-stimulated receptor expressed on QRFP-neurons, which helped mind? These are some of the many questions that mice were comfortable below 30 degrees Celsius us to stimulate them. With these mice, we were able will be fascinating to explore now that we can induce (86 degrees Fahrenheit), to induce more than 48 hours of a hibernation-like hibernation states in one of our main mammalian when normally they would be cold. This suggested that state within 30 minutes of injecting into the stomach research models. their set body temperature compounds with ligands to the G protein-coupled Eventually, it’s possible that long-term hibernation had been lowered in a receptor, a speed that bodes well for the possibilities in humans could be a game changer for space travel, manner reminiscent of a deep hibernation state. of use in medical triage. For 48 hours or more, we healthcare and even climate change. And like genomic observed the body temperature of our QFRP-neu- medicine, which once seemed so far away, there will ron-stimulated mice lowered below 30 degrees Celsius be ethical considerations. What does consent look like (86 degrees Fahrenheit) and it even dropped to 24 to a hibernating human? Will hibernators pay taxes? degrees Celsius (75 degrees Fahrenheit) under cold And when are you really terminally ill? We need to conditions. Their heart rate, oxygen consumption and start exploring these questions, as the last year has respiration rate were also all reduced. And we have shown us that the science in this area can rapidly also been able to replicate this in rats, a species that jump forward. If long-term hibernation is possible, neither hibernates nor has daily torpor. it could change our concept of time entirely: could In the future, slowing metabolic processes like this we hibernate through a pandemic, or hit pause and might give stroke, heart attack and trauma victims wait for the planet to repair itself? These are questions more time before tissue damage becomes too severe that our children may have to answer, which is an to treat. Dormancy could also extend the viability of exciting thought. organ transplants. Currently, a waiting kidney or liver can be preserved in cold solutions for only 24 hours, while a heart or a lung is viable for a mere four to six REFERENCE hours. If we could slow the degradation rate by 90% For a full list of references, please check the that would be huge. With an eye to this, the next online version of this article: https://www.riken.jp/

step for us at RIKEN is to try to induce hibernation en/news_pubs/research_news/ © EDWARD KINSMAN / SCIENCE PHOTO LIBRARY

28 RIKEN RESEARCH FEATURES

WINTER 2020 29 FEATURES

e are one step closer to devices that exciting finding is that when conditions are tweaked can control the direction and power in accordance with theory, the sound waves travel in of sound waves. A team led by Yoshi- only one direction. chika Otani at the RIKEN Center Wfor Emergent Matter Science (CEMS) has fabricated ONE DIRECTION TUNE a magnetic film in which sound waves interact with It was only during the review process of their research electron spins, so that the amplitude and direction paper that the team realized that they had achieved of sound waves can be manipulated with a similar 100% ‘rectification’. Rectifiers are essentially one-way degree of control as electrical currents. streets that allow energy to flow in a single direction. The interaction involves ‘magneto-rotation One of the reviewers noted theory predicted that coupling’, which is when the rotational motion complete rectification should be possible, and when of surface sound waves causes the atomic lattice the team re-examined their data, they found that their in a ferromagnetic material to move in a circular measurements did indeed show 100% rectification — motion. The magnetism of a ferromagnet, the classic a big increase over the previous record of 20%. example of which is the bar magnet, derives from the Importantly, the amount of rectification can be spins of their electrons tending to align in the same easily controlled. “The magnetic field controls how direction. Coupling makes the magnetization precess, much you block the sound waves traveling in one a wobbling motion that occurs when a spinning direction,” says Jorge Puebla, one of the co-authors object is the subject of an external force. Depending from CEMS. “So you could have a knob on your on the direction of the sound waves, this precession device that adjusts how much sound comes in from can weaken the waves or leave them unaffected. An the outside and how much you block, for example.” Puebla notes that the sound waves used in this experiment are too high in frequency to be audible to people, so this will require further study for more conventional sound blocking uses. However, this MINGRAN XU | Student Trainee, Quantum Nano- finding could be more immediately useful in sound Scale Magnetism Research Team, RIKEN Center for Emergent Matter Science isolators for other types of experiments. In addition, electrical rectifiers that permit electric Mingran Xu is a PhD later by a three-year currents to flow one direction but not the other course student at Japan Society for the are used extensively in the electronics industry. Graduate School of Promotion of Science For example, they can be used to convert alternat- Frontier Sciences at fellowship (JSPS DC1). ing electric currents into steady direct currents. University of Tokyo He has been working and a research student on a spin conversion Now, acoustic rectifiers based on magneto-rotation at RIKEN. He was project since began coupling are a possibility, and might be useful in first supported by the his masters. His devices such as sound isolators and specialized RIKEN International research is focused magnetic properties sensors, which could be applied Program Associate on magnon–phonon to superconductivity research among other areas. (IPA) Program, and coupling systems. A FAMILIAR NAME JORGE PUEBLA | Research scientist, Quantum Ferromagnetism is an old technology, dating back Nano-Scale Magnetism Team, RIKEN Center for at least two and a half millennia. But what has made Emergent Matter Science this new control possible is the advancement of the emerging field of spintronics. The technology of During his PhD and worked as spintronics uses the spins of electrons rather than Jorge Puebla studied the project leader their charges (as in conventional electronics) to spin phenomena in technology in semiconductor developments convey information. It’s seen as promising for creating nanostructures in microscopy, devices that have ultralow power consumption, as (quantum dots interferometry and spin can flow without electrons physically moving. and wires) in the photovoltaics for the One way to create and manipulate the flow of spins, or Department of Physics German company spin currents, is to use sound waves in ferromagnetic and Astronomy at the Attocube Systems. materials. Sound waves that travel as ripples along University of Sheffield In 2015, he joined in the United Kingdom. RIKEN, where he leads the surface of a ferromagnetic material displace the Later, he was the projects on photon electron spins, giving rise to a spin current. Known as recipient of a Marie coupling and phonons magnetoelastic coupling, this effect has been exten- Curie Fellowship with spin systems. sively studied for some time. However, the team was surprised when they

30 RIKEN RESEARCH FEATURES

NOISE CONTROL Sound waves traveling on the surface of a magnetic film (blue) interact with the magnetism differently depending on which direction they travel in. This effect could be used to make acoustic rectifiers. Figure provided by Mari Ishida.

Rotational motion lattice of ω -k

Precession motion of M

coupling they had observed. They uncovered a theo- you need extremely small structures to fabricate a retical paper in the proceedings of a 1976 conference high-frequency device. It was really quite challenging that predicted the effect, and the name of the first to make.” author of the paper, Sadamichi Maekawa, looked The team now intends to use magneto-rotation very familiar. In fact, he was a CEMS colleague coupling to explore magnetism in exotic two-dimen- who was working two floors below the team’s lab. sional materials. “Two-dimensional materials with The experimental observation of an effect that he magnetism have been discovered and some of them predicted more than 40 years ago was sweet vindica- have magnetism out of the plane,” says Puebla. “But tion for Maekawa: “I had almost forgotten about my when you consider that these materials are just one work, but I was very happy when Dr Puebla discov- or two atoms thick, it’s not really clear where this ered my paper.” Puebla concurs: “It was a very nice anisotropy is coming from. We want to fabricate some surprise to discover that we had someone to talk to devices and see if we can contribute to this important who was so nearby.” question in two-dimensional materials. One reason it had taken so long to observe the effect is that the experiment needed to be performed REFERENCE at high frequencies, which requires small structures. Xu, M., Yamamoto, K., Puebla, J., Baumgaertl, Recent advances in nanofabrication have made it K., Rana, B., Miura, K., Takahashi, H., Grundler, possible to make devices small enough to perform D., Maekawa, S. & Otani, Y. Nonreciprocal the measurement. “If you want to analyze this effect surface acoustic wave propagation via magneto- you need a really high-frequency device,” explains rotation coupling. Science Advances 6,

WINTER 2020 31 INFOGRAPHIC

HOW BEST TO MAP TISSUE CELLS The most powerful of 13 single-cell RNA sequencing methods tested by an international group for their ability to map the cells in complex tissues is Quartz-Seq2. Developed by Itoshi Nikaido, Yohei Sasagawa and colleagues of the RIKEN Center for Biosystems Dynamics Research, Quartz-Seq2 best identified cell types and most finely distinguished between changing cell states via the measures listed below. The study was designed to help large-scale collaborative tissue mapping projects, such as the Human Cell Atlas, as they seek to standardize sequencing methods globally.

GENE DETECTION MARKER CLUSTERABILITY MAPPABILITY MIXABILITY 747–755 (2020). DOI:10.1038/s41587-020-0469-4 38, 38, EXPRESSION Nat Biotechnol Nat

The expression levels of cell-type protein signatures This is the probability of cells The number of genes produced, which being clustered with cells able to be detected, also determines a of the same type in analysis, which relies on a method’s ability to in other words a method’s method’s sensitivity detect genes. ability to discriminate between The ability of a to gene markers cell types. method to predict This is the ability and its gene library *Quartz-Seq2 has and produce a of protocols to be complexity. This will strong poly(A) Integrated clusterabilty is map of a tissue’s combined without a determine the detail tagging, which clusterability when different cells in a way able drop in their power in tissue profiles increases the methods are used and to be used with a to discriminate produced. amplified cDNA yield. corrected for. reference atlas. between cell types. Benchmarking single-cell RNA-sequencing protocols for cell atlas projects atlas cell single-cellfor Benchmarking RNA-sequencing protocols etal

THE SCORE BOARD

Protocol name Gene detection Marker expression Clusterability Integrated clust. Mappability Mixability Total score

Quartz-seq2 Developed at RIKEN

Top 3 Top Chromium

Smart-seq2

CEL-seq2

C1HT-medium

C1HT-small

ddSEQ

32 RIKEN RESEARCH RIKEN’S CENTERS AND FACILITIES across Japan and around the world

LEGEND WAKO ● (RIKEN’s Headquarters) Strategic Research Center ■ Research Infrastructure Center ● Interdisciplinary Theoretical and ◆ Large Research Infrastructure Mathematical Sciences Program (iTHEMS) ▲ Research Cluster ● Center for Brain Science (CBS) ▼ Other ● Center for Sustainable Resource Science (CSRS) ● Center for Emergent Matter Science (CEMS) ● Center for Advanced Photonics (RAP) ● Nishina Center for Accelerator-Based Science (RNC) ▲ Cluster for Science, Technology, and Innovation Hub (CSTIH) ▲ Cluster for Pioneering Research (CPR) ◆ Radio Isotope Beam Factory (RIBF) ▼ Head Office for Information Systems and Cybersecurity SENDAI ● Center for Advanced Photonics (RAP)

YOKOHAMA ● Center for Integrated Medical Sciences (IMS) ● Center for Biosystems Dynamics Research (BDR) TSUKUBA ● Center for Sustainable Resource Science (CSRS) ■ BioResource Research ■ SPring-8 Center (RSC) Center (BRC) ▲ Cluster for Science, Technology, and Innovation Hub (CSTIH) ◆ BioResource ◆ Genome Sequencing ◆ Nuclear Magnetic Resonance (NMR) TOKYO ● Center for Advanced Intelligence Project (AIP) HARIMA ▼ Innovation Design Office ■ SPring-8 Center (RSC) ◆ SPring-8 ◆ SACLA NAGOYA

KEIHANNA ● Center for Advanced Intellegence Project (AIP) ■ BioResource Research Center (BRC) KOBE ● Center for Biosystems Dynamics Research (BDR) ■ Center for Computational Science (R-CCS) ▲ Cluster for Science, Technology, and Innovation Hub (CSTIH) OSAKA ◆ Molecular Imaging ● Center for Biosystems ◆ Supercomputer Fugaku Dynamics Research (BDR)

Since relocating its original campus from central Tokyo Singapore and other countries. To expand our network, to Wako on the city’s outskirts in 1967, RIKEN has rapidly RIKEN works closely with researchers who have returned to expanded its domestic and international network. their home countries or moved to another institute, with help RIKEN now supports five main research campuses in Japan from RIKEN’s liaison offices in Singapore, Beijing and Brussels. and has set up a number of research facilities overseas. In addition to its facilities in the United States and the United For more information, please visit: Kingdom, RIKEN has joint research centers or laboratories www.riken.jp/en/research/labs/ in Germany, Russia, China, South Korea, India, Malaysia, www.riken.jp/en/collab/research/ www.riken.jp/en

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