Research News KYOT

Kyoto University 2019 Spring On the occasion of Tasuku Honjo’s Nobel Prize

The streets of Stockholm are cold in December. As science’s outcomes must further peace and the betterment of president, I was fortunate to join Tasuku Honjo there and life on the planet, in line with Nobel’s vision for the prizes. attend the ceremony and banquet. It was both an immense Dr Honjo joins Shinya Yamanaka as our second, active honor and an unforgettable experience. medicine laureate among the research faculty. Both continue to Walking the cobbled lanes and seeing the holiday lights and be leaders in their fields, seeking to improve the lives of decorations, I felt the immense sense of history and tradition patients worldwide through diligent pursuit of knowledge in surrounding the prize, which Alfred Nobel established in 1895, basic science. two years before the founding of our University. In March 2018, Kyoto University implemented a policy of Nobel laureates have shaped popular thought and under- not accepting research funding from military sources. Life on standing of the world far beyond their own fields of study. It is this planet is too precious and too fragile to be remarkable to feel this power in Stockholm, where Marie Curie placed in any more jeopardy than it currently and Alfred Einstein also trod the paving stones. And Japan’s first faces. We will do our utmost to imbue our laureate, Hideki Yukawa, who had been an undergraduate and graduates and researchers with this guiding then later full professor in Kyoto, inspired our war-ravaged principle, as well as a desire for harmonious nation when he received the physics prize in 1949. coexistence with all life and the natural Yukawa’s message to Japan and the world was that science environment. should represent the best that humanity has to offer: that Juichi Yamagiwa, President

Contents Editorial team 03 On the cover: KURN Editorial Board, assisted by the Offices of Public Relations, Research Administration Congratulations, (KURA), and International Strategy (iSO-KU) Publisher: TRAIS K.K. Contact: Kyoto University, Japan Honjo-sensei! +81 75.753.7531 [email protected]

Roundtable discussions 04 Defining ‘Kyotoness’ in the research environment 08 Driven by curiosity

10 Cutting edge 15 KyotoU today 15 Science with industry 16 News from overseas centers 18 Student voices On the cover An ukiyo-e (traditional woodblock print) style 19 Eternal aesthetic design, featuring Nobel laureate Tasuku Honjo in his ceremonial garb, an oni-taiji themed depiction of T-cells battling ogre-like cancer cells (read clockwise from upper-right), and a scene of the medical school campus in spring. Can you recognize some notable KyotoU figures among the cherry-viewing crowd? (Trais/Fujiwara) © Nobel Media AB/Nanaka Adachi On the cover: Nobel Prize 2018

Congratulations, Honjo-sensei! Join us in this special issue as we celebrate the 2018 Nobel Prize in Physiology or Medicine, awarded jointly to Tasuku Honjo, distinguished professor of Kyoto University, and James P Allison, of the University of Texas, “for their discovery of cancer therapy by inhibition of negative immune regulation.”

This spring issue’s first section follows Honjo from the announcement of the prize in early October, to his attendance at ‘Nobel week’ in Stockholm in early December, and then to his return to Kyoto later that month. Interspersed are discussions he had with prominent KyotoU scholars and an introduction to the science behind PD-1 and cancer immunotherapy.

Kyoto U Research News 2019 Spring | 03 Congratulations, Honjo-sensei!

and ExecVP/Provost Nagahiro Minato sat to Honjo boarded to whisk them past kyô-sei, or “Without ambition, nothing is Mixing descriptions of the scientific laureates and their families elaborate dressing — and for the ladies, leisurely consumed a banquet dinner down in front of the amassed reporters the crowds and entry procedures. acheived”. processes with anecdotes about his life and guests joined mem- hairdressing — associated with interspersed with music and dance and cameras for their first press confer- Within minutes they were in their black, The highlight of the afternoon was a and numerous collaborators, he painted bers of the Swedish royal Japanese traditional formal wear. performances and endless conversations ence. chauffeured Nobel vehicle, on their way joint press conference at the Nobel a picture of the immense complexity that family for a gala Nobel Honjo’s black haori hakama, embla- around the long tables. With much The most indelible image of the to downtown Stockholm. Forum, during which Honjo and exists in all our bodies, ending on the concert at the Stockholm zoned with his family crest, was noted fanfare, Honjo had the honor of deliver- evening, first released by the Nobel Nobel week Meanwhile a jostling crowd of Allison’s discussions of their research note that we have evolution to thank for Concert Hall, which moist eyes, Honjo spoke to Swedish in the Swedish media as being a breath ing a final speech (see below), marking young researchers, who peppered the the Honjos sped off to Arlanda and the Foundation, was of Honjo surrounded Wednesday 5 December, early morning. Japanese reporters and news cameras and consequences for cancer treatment the intricate systems that maintain our would then become the television crews covering the event of of fresh air amongst an “ocean of the end of the meal and the beginning of two with deep and probing scientific voyage home. by celebrating lab members. The Dr and Mrs Honjo arrived at Kansai were waiting on the edges of the red were interspersed with lighter moments health. The hour-long speech was venue for Monday’s award ceremony. how much it means to him to see the tuxedoes”. The weather, which had further festivities that would continue questions, often bringing out the humor photograph — taken at the behest of International Airport, where a room full carpet in front of the Grand Hôtel, about their personal lives. widely praised as being one of the best Sunday was punctuated with meet- positive effects of what he had achieved. been largely grey up to that point, throughout the night, concurrent to in the two men. The afternoon saw all The return Stockholm using Honjo’s own phone — of reporters queried him on his final craning to catch a glimpse of the new Friday 7 December. Honjo had stated on record by any laureate. ings such as with KyotoU’s Yamagiwa Later in the afternoon there was some suddenly brightened as the winter sun Swedish observation of the festival of St the laureates reunited at the Concert captured the global flavor of his research thoughts before departure. Ending laureate as he stepped out of the car. before departing from Japan that he was Saturday and Sunday 8–9 December. and Minato (see below), and an short time for a family outing, to see the lightened the sky and the city. Lucia. Hall, this time for a recording of the Friday 14 December. The initial mass of team. weeks of speculation, he announced his Nobel week had begun. particularly looking forward to his official With the hard work under his belt, emotional event where Honjo and historic sailing vessel Vasa. While the At the ceremony itself, where Tuesday and Wednesday 11–12 annual “Nobel Minds” program for the reporters in Stockholm had dwindled to The following morning, Honjo was intention to donate a majority of his Thursday 6 December, morning. Nobel lecture, and this moment came Honjo could now concentrate on many Allison met with cancer survivors whose museum housing the immense, Honjo and his Nobel peers received Suite, followed by the full orchestra, Laureates and guests then followed December. Following such a long day BBC and Swedish national television. a handful by the end of Nobel week, but back at the Clock Tower for more in a prize money to a fund to support early Laureates, accompanied by their families on Friday afternoon at the immense Aula other, lighter activities, while preparing lives had been saved thanks to the two preserved ship is open to the public, certificates and medals from the illustrating newly found vigor in a fight the King and royal family to the vast Blue and night, most laureates chose not Thursday 13 December. The final day upon setting foot in Osaka, Honjo was continuing round of interviews, congrat- career researchers. and guests, gathered at the nearby Medica of the Karolinska Institutet. for Monday’s ceremony and banquet. scholars’ research. After many hugs and only visiting heads of state and Nobel Swedish monarch, King Carl XVI against cancer cells. Hall of the historic Stadshus, where they schedule anything immediately afterward, but Honjo was active as was back to grey skies, as the Honjos quickly reminded of the baited breath ulatory phone calls, and a more personal The Honjos, accompanied by Nobel Museum for a half-day of Speaking to a capacity crowd of medical Saturday started with a Japanese press laureates are allowed to actual go Gustaf, the assembled were treated to always, attending a luncheon at the paid farewell to the hotel staff and made with which the news media were still press conference together with his wife University support staff, then boarded a informal welcoming into the traditions of students, young scientists, and ordinary interview, followed by a reception and onboard. an enlightening musical rendition of Japanese ambassador’s residence and their way to the Nobel Foundation. following his movements. Displaying the Shigeko. flight en route first to Helsinki. the institution, as well as an opportunity citizens inspired by his work, Honjo press conference hosted by the Japanese Monday 10 December. The long- how Honjo and Allison’s discoveries then being joined by chemistry laureate Here, as tradition dictates, Honjo sat in Nobel medal for the first time to the Same day, late evening. As soon as the to sign one of the café chairs. Honjo delivered a passionate account of his ambassador to Sweden and including a anticipated day of greatest pomp and released the ‘brakes’ on the body’s Frances Arnold for an open discussion at Alfred Nobel’s chair to sign a book of press gathered outside the arrivals area The interim Honjos’ Finnair plane parked at the gate donated a framed, four-character saying, decades-long quest to unravel the courtesy visit with the Swedish minister circumstance began quietly with a immune system, first with a solo violin the Swedish parliament, where young laureates, remarking that the experience at KIX, Honjo renewed his determination at Stockholm’s Arlanda Airport, the written in his own hand, reading: yû-shi mysteries of the body’s immune system. for science. In the evening, all the rehearsal in the morning, followed by playing a melody from Bizet’s Carmen legislators with a science and health of being in that place, as with Einstein to continue supporting younger October and November. The initial Swedish government’s attaché assigned policy bent asked the two luminaries for and Yukawa and many more before colleagues, advancing his field, and excitement of the announcement was their opinions on promoting science him, left a deep impression on him. promoting basic research across the followed by two frenzied months, during education and improving public health. Taking a wreath then to Nobel’s grave, nation. The announcement which Honjo made government A second session of dressing and Monday 1 October 2018, shortly past courtesy calls in Tokyo, gave numerous hairdressing followed, ahead of an 18.30. With a bevy of news trucks television interviews, and started into his evening’s banquet as guests of the royal parked outside the Clock Tower in preparations for the trip to Sweden, all house, in the stately palace just across anticipation, the live stream from while continuing his typically non-stop the channel from the Grand Hôtel. Stockholm broke the news of Honjo and schedule of research meetings and Then on Wednesday morning Honjo Allison’s joint award. A few minutes appearances. and Allison paid a final visit to Karolins- later, Honjo, President Juichi Yamagiwa, ka, this time for an informal session with

three universities, and when I returned “For example in immunology,” says faculty that we needed more knowl- experiences and knowledge can lead Defining ‘Kyotoness’ in the research environment to Kyoto, I realized that the environ- Honjo, “I was a total newcomer. Dr edge about the scientific foundations, to new and unexpected outcomes. ment of the medical school was Minato helped me understand what and he pointed the way for us.” “What makes Kyoto a special place “I have an unusual boast,” says Honjo Japan who have been on the payroll afternoon with two colleagues, Drs particularly open to sharing knowl- was what.” It is an enlightening moment, for you, as a researcher?” probes wryly, “for there are not many in of all three universities of Tokyo, Yamagiwa and Minato, respectively edge.” Minato laughs at Honjo’s unexpect- demonstrating how cross-seeding of Yamagiwa. Osaka, and Kyoto.” the President and the Executive Vice ed show of modesty. “Our field was “The quiet, peaceful atmosphere,” These experiences, together with President for research/Provost. really not very rigorous until Dr Honjo says Honjo, “and the freedom to time spent in the United States, have Yamagiwa is a preeminent primatolo- appeared. It was interesting, and there pursue your curiosity. For years we given him a unique perspective in gist, and Minato, in addition to being was a great deal of fascinating work didn’t know what PD-1 did, but we did understanding what makes Kyoto a a leading immunologist, is a long-time going on, but a solid, molecular and have a feeling it must be important. special place for a researcher. collaborator of Honjo’s. genetic foundation for the processes “When all the pieces came into In an historic salon room at the “Throughout my career, I have been we were observing had yet to be place, the link to cancer became Grand Hôtel, overlooking Stockholm fortunate to be able to learn from established. obvious to us, thanks to having had harbor, Honjo managed to take a others, without having to study “Dr Honjo arrived and immediately the time to discover this and a lack of short break from his hectic Nobel everything from the basics myself. began asking pointed questions. It constraints. Kyoto made this possible week schedule to sit down on Sunday This ‘ear-training’ served me well at all quickly dawned on the younger for us.”

04 | Kyoto U Research News 2019 Spring Nobel Prize 2018

three universities, and when I returned “For example in immunology,” says faculty that we needed more knowl- experiences and knowledge can lead to Kyoto, I realized that the environ- Honjo, “I was a total newcomer. Dr edge about the scientific foundations, to new and unexpected outcomes. ment of the medical school was Minato helped me understand what and he pointed the way for us.” “What makes Kyoto a special place “I have an unusual boast,” says Honjo Japan who have been on the payroll afternoon with two colleagues, Drs particularly open to sharing knowl- was what.” It is an enlightening moment, for you, as a researcher?” probes wryly, “for there are not many in of all three universities of Tokyo, Yamagiwa and Minato, respectively edge.” Minato laughs at Honjo’s unexpect- demonstrating how cross-seeding of Yamagiwa. Osaka, and Kyoto.” the President and the Executive Vice ed show of modesty. “Our field was “The quiet, peaceful atmosphere,” These experiences, together with President for research/Provost. really not very rigorous until Dr Honjo says Honjo, “and the freedom to time spent in the United States, have Yamagiwa is a preeminent primatolo- appeared. It was interesting, and there pursue your curiosity. For years we given him a unique perspective in gist, and Minato, in addition to being was a great deal of fascinating work didn’t know what PD-1 did, but we did understanding what makes Kyoto a a leading immunologist, is a long-time going on, but a solid, molecular and have a feeling it must be important. special place for a researcher. collaborator of Honjo’s. genetic foundation for the processes “When all the pieces came into In an historic salon room at the “Throughout my career, I have been we were observing had yet to be place, the link to cancer became Grand Hôtel, overlooking Stockholm fortunate to be able to learn from established. obvious to us, thanks to having had harbor, Honjo managed to take a others, without having to study “Dr Honjo arrived and immediately the time to discover this and a lack of short break from his hectic Nobel everything from the basics myself. began asking pointed questions. It constraints. Kyoto made this possible week schedule to sit down on Sunday This ‘ear-training’ served me well at all quickly dawned on the younger for us.”

Kyoto U Research News 2019 Spring | 05 Congratulations, Honjo-sensei!

06 | Kyoto U Research News 2019 Spring Nobel Prize 2018

and ExecVP/Provost Nagahiro Minato sat to Honjo boarded to whisk them past kyô-sei, or “Without ambition, nothing is Mixing descriptions of the scientific laureates and their families elaborate dressing — and for the ladies, leisurely consumed a banquet dinner down in front of the amassed reporters the crowds and entry procedures. acheived”. processes with anecdotes about his life and guests joined mem- hairdressing — associated with interspersed with music and dance and cameras for their first press confer- Within minutes they were in their black, The highlight of the afternoon was a and numerous collaborators, he painted bers of the Swedish royal Japanese traditional formal wear. performances and endless conversations ence. chauffeured Nobel vehicle, on their way joint press conference at the Nobel a picture of the immense complexity that family for a gala Nobel Honjo’s black haori hakama, embla- around the long tables. With much The most indelible image of the to downtown Stockholm. Forum, during which Honjo and exists in all our bodies, ending on the concert at the Stockholm zoned with his family crest, was noted fanfare, Honjo had the honor of deliver- evening, first released by the Nobel Nobel week Meanwhile a jostling crowd of Allison’s discussions of their research note that we have evolution to thank for Concert Hall, which moist eyes, Honjo spoke to Swedish in the Swedish media as being a breath ing a final speech (see below), marking young researchers, who peppered the the Honjos sped off to Arlanda and the Foundation, was of Honjo surrounded Wednesday 5 December, early morning. Japanese reporters and news cameras and consequences for cancer treatment the intricate systems that maintain our would then become the television crews covering the event of of fresh air amongst an “ocean of the end of the meal and the beginning of two with deep and probing scientific voyage home. by celebrating lab members. The Dr and Mrs Honjo arrived at Kansai were waiting on the edges of the red were interspersed with lighter moments health. The hour-long speech was venue for Monday’s award ceremony. how much it means to him to see the tuxedoes”. The weather, which had further festivities that would continue questions, often bringing out the humor photograph — taken at the behest of International Airport, where a room full carpet in front of the Grand Hôtel, about their personal lives. widely praised as being one of the best Sunday was punctuated with meet- positive effects of what he had achieved. been largely grey up to that point, throughout the night, concurrent to in the two men. The afternoon saw all The return Stockholm using Honjo’s own phone — of reporters queried him on his final craning to catch a glimpse of the new Friday 7 December. Honjo had stated on record by any laureate. ings such as with KyotoU’s Yamagiwa Later in the afternoon there was some suddenly brightened as the winter sun Swedish observation of the festival of St the laureates reunited at the Concert © Nobel Media AB/Alexander Mahmoud captured the global flavor of his research thoughts before departure. Ending laureate as he stepped out of the car. before departing from Japan that he was Saturday and Sunday 8–9 December. and Minato (see below), and an short time for a family outing, to see the lightened the sky and the city. Lucia. Hall, this time for a recording of the Friday 14 December. The initial mass of team. weeks of speculation, he announced his Nobel week had begun. particularly looking forward to his official With the hard work under his belt, emotional event where Honjo and historic sailing vessel Vasa. While the At the ceremony itself, where Tuesday and Wednesday 11–12 annual “Nobel Minds” program for the reporters in Stockholm had dwindled to The following morning, Honjo was intention to donate a majority of his Thursday 6 December, morning. Nobel lecture, and this moment came Honjo could now concentrate on many Allison met with cancer survivors whose museum housing the immense, Honjo and his Nobel peers received Suite, followed by the full orchestra, Laureates and guests then followed December. Following such a long day BBC and Swedish national television. a handful by the end of Nobel week, but back at the Clock Tower for more in a prize money to a fund to support early Laureates, accompanied by their families on Friday afternoon at the immense Aula other, lighter activities, while preparing lives had been saved thanks to the two preserved ship is open to the public, certificates and medals from the illustrating newly found vigor in a fight the King and royal family to the vast Blue and night, most laureates chose not Thursday 13 December. The final day upon setting foot in Osaka, Honjo was continuing round of interviews, congrat- career researchers. and guests, gathered at the nearby Medica of the Karolinska Institutet. for Monday’s ceremony and banquet. scholars’ research. After many hugs and only visiting heads of state and Nobel Swedish monarch, King Carl XVI against cancer cells. Hall of the historic Stadshus, where they schedule anything immediately afterward, but Honjo was active as was back to grey skies, as the Honjos quickly reminded of the baited breath ulatory phone calls, and a more personal The Honjos, accompanied by Nobel Museum for a half-day of Speaking to a capacity crowd of medical Saturday started with a Japanese press laureates are allowed to actual go Gustaf, the assembled were treated to always, attending a luncheon at the paid farewell to the hotel staff and made with which the news media were still press conference together with his wife University support staff, then boarded a informal welcoming into the traditions of students, young scientists, and ordinary interview, followed by a reception and onboard. an enlightening musical rendition of Japanese ambassador’s residence and their way to the Nobel Foundation. following his movements. Displaying the Shigeko. flight en route first to Helsinki. the institution, as well as an opportunity citizens inspired by his work, Honjo press conference hosted by the Japanese Monday 10 December. The long- how Honjo and Allison’s discoveries Considering that the chance of such mutation and then being joined by chemistry laureate Here, as tradition dictates, Honjo sat in Nobel medal for the first time to the Same day, late evening. As soon as the to sign one of the café chairs. Honjo delivered a passionate account of his ambassador to Sweden and including a anticipated day of greatest pomp and released the ‘brakes’ on the body’s Honjo’s speech at the Nobel banquet selection must be unbelievably low, we human beings are Frances Arnold for an open discussion at Alfred Nobel’s chair to sign a book of press gathered outside the arrivals area The interim Honjos’ Finnair plane parked at the gate donated a framed, four-character saying, decades-long quest to unravel the courtesy visit with the Swedish minister circumstance began quietly with a immune system, first with a solo violin “Your Majesties, your Royal highnesses, excellencies, dear all very fortunate. the Swedish parliament, where young laureates, remarking that the experience at KIX, Honjo renewed his determination at Stockholm’s Arlanda Airport, the written in his own hand, reading: yû-shi mysteries of the body’s immune system. for science. In the evening, all the rehearsal in the morning, followed by playing a melody from Bizet’s Carmen laureates, ladies and gentlemen, Jim and I both know that the development of our legislators with a science and health of being in that place, as with Einstein to continue supporting younger October and November. The initial Swedish government’s attaché assigned On behalf of [fellow laureate] Professor Jim Allison and discovery is just beginning, as currently only 20 to 30 policy bent asked the two luminaries for and Yukawa and many more before colleagues, advancing his field, and excitement of the announcement was myself, I wish to express our heartful appreciation to the percent of patients respond to the immunotherapy. Andy their opinions on promoting science him, left a deep impression on him. promoting basic research across the The announcement followed by two frenzied months, during Nobel Assembly of the Karolinska Institute and the Nobel Coghlan and Dan Chen described our discovery as the education and improving public health. Taking a wreath then to Nobel’s grave, nation. which Honjo made government Foundation. cancer equivalent of penicillin, which gave rise to a whole A second session of dressing and Monday 1 October 2018, shortly past courtesy calls in Tokyo, gave numerous Cancer has been the number one cause of death during generation of antibiotics that changed medicine, and hairdressing followed, ahead of an 18.30. With a bevy of news trucks television interviews, and started into his the last half-century. The trend is getting even worse as the consigned most previously fatal infections to history. We evening’s banquet as guests of the royal parked outside the Clock Tower in preparations for the trip to Sweden, all average life span increases. encourage many more scientists to join us in our efforts to house, in the stately palace just across anticipation, the live stream from while continuing his typically non-stop The concept of cancer immunotherapy was theoretical- keep improving cancer immunotherapy. We sincerely the channel from the Grand Hôtel. Stockholm broke the news of Honjo and schedule of research meetings and ly proposed by the Australian Nobel laureate Sir Frank hope this treatment will reach far and wide so that Then on Wednesday morning Honjo Allison’s joint award. A few minutes appearances. Macfarlane Burnet over sixty years ago, and since then, a everybody on our planet can benefit from this evolution- and Allison paid a final visit to Karolins- later, Honjo, President Juichi Yamagiwa, large number of people have tried to apply it, but without ary gift for healthy life. ka, this time for an informal session with success. This was probably because their efforts focused Jim and I acknowledge that we were selected for this on pushing the accelerators of the immune system. Jim highest of all scientific honors. We accept the distinction and I independently discovered that the reactivation of the with our deepest gratitude for the great institutions that immune system by blocking two major negative regula- have supported our work, for our many devoted and tors, CTLA4 and PD-1, can cure a significant portion of skilled coworkers, without whom our achievements cancer patients. Fortunately, our experiments in mouse would have been impossible, and, finally, for Alfred Nobel models were successfully applied to humans. As a result, for his wisdom to institute the prize and the people of Jim and I have experienced many occasions that have Sweden for a fantastic Nobel Week. made us feel well rewarded, such as meeting cancer Thank you.” patients who say their lives were saved by our therapies. Cancer immunotherapy is possible because we have a highly sophisticated immune system called ‘acquired immunity’, which can catch small changes in tumor cells. How could we develop such a sophisticated immune recognition system that employs gene rearrangement? The genetic rearrangement mechanism must have developed accidentally — probably about five hundred million years ago, when vertebrates evolved. Thereafter, it must have persisted through natural selection due to the advantage of surviving infectious diseases. © Nobel Media AB/Dan Lepp

Kyoto U Research News 2019 Spring | 07 Congratulations, Honjo-sensei!

the historic Memorial Auditorium on the sense, the life of a researcher isn’t for Yamanaka: Dr Honjo puts it very well. I began my career as an orthopedic was excited by this unexpected Driven by curiosity med school campus. An excerpt follows. everyone. It’s not something you can You must enjoy what you are doing in surgeon, something I wanted to be from result. just stumble into. If you find yourself order to be a scientist. a young age. But I soon realized that I This experience galvanized my idea of Nowhere else in Asia can you find a Minato: In closing, we all have different asking “what should I do?” then that’s wasn’t very good at it, becoming a researcher; I simply followed single university with two Nobel reasons for being researchers, but what not the right mindset. so I tried my hand at the questions and results that interested laureates active among its research motivates you? What is your approach to To be a scientist, you need a constant research. me. I then went to the United States to faculty. Curious as to what might result devoting your life to science? drive of curiosity and the motivation to In one of my first study arteriosclerosis, but when the gene from a discussion between the two pursue the answers on your own. As experiments I had to I was focusing on was linked to cancer, I scientists — Dr Honjo and Shinya Honjo: Research has always been a joy children, everyone has the potential to test a drug that became fascinated with cancer research. Yamanaka, the director of the Center for for me; I can’t recall a moment when become anything. As you then grow up, would raise the Cancer then led me to stem cells. iPS Cell Research and Application, CiRA, I’ve suffered so much that I wanted to you learn your likes and limits, and a blood pressure of a I was always simply pursuing my and the 2012 Nobel laureate in stop doing it. vision of yourself takes shape. mouse. Surprisingly, curiosity. Dr Honjo and I have followed medicine — ExecVP/Provost Minato Nonetheless there comes a moment I chose the study of immunology. I the blood pressure different, but equally valid paths. The suggested that an open discussion would when anyone seeks deeper meaning wish you all the best as you seek to find fell! But what most common threads are that we both have be good for students, and a special event in life, whether to make money, or to what is your lifelong motivation. astonished me was immense curiosity and the motivation to was arranged for 27 December 2018 in pursue something for love. In that my own reaction: I try to find answers to the unexpected.

08 | Kyoto U Research News 2019 Spring Nobel Prize 2018

One of the ways cancer cells avoid What is PD-1, and why a Nobel prize for it? being detected by our immune system is Understanding how the immune system can be coaxed to fight cancer by blocking the PD-1 receptor with another receptor, PD-L1. When PD-L1 Cancer is caused by irregular division system’s infantry, carrying receptors on on a cancer cells binds with PD-1 on a and proliferation of our own cells. their surfaces for detecting unwanted T-cell, it steps on the ‘brake’, protecting Normally, the immune system identifies outsiders. the cancer. and eliminates such anomalies, but However, an intricate balance must The immune system is tricked into under some circumstances these cells be maintained so that the body doesn’t thinking that the cancer is a normal part evade natural defenses and grow to the attack itself. When this occurs, such as is of the body. point of threatening essential body suspected in the case of dangerous So by stopping these receptors from functions. allergic reactions, the result can be swift binding, Honjo developed a way to Surgery, radiation, and chemotherapy and fatal. release the brake, freeing the immune are established methods of cancer In 1992, Tasuku Honjo discovered system to fight the abnormal cells. combat, and even the idea of recruiting PD-1, a protein on the surface of 22 years after the discovery of PD-1, a the immune system in the fight isn’t new. T-cells. While not immediately sure cancer drug based on Honjo’s finding As stated in his banquet speech, Honjo of its function, years of diligent was first approved for use in Japan, gives credit for the concept to a 1960 experiments led him and his team sending a shockwave through the world medicine laureate. For decades it just to a realization that the protein acts of cancer treatment. wasn’t clear how to actually make this as a ‘brake’ on the T-cell, stopping But as is often the case in science, work. it from causing an immune these few answers generated even more The immune system is the body’s way response. Eventually they recog- questions, and Honjo states frequently to find and eliminate harmful, foreign nized further that blocking PD-1 that he cannot retire, because “there is elements, such as invasive bacteria and could activate the immune system still so much that we simply don’t viruses. Specialized ‘T’ cells are the to attack cancer. know.”

the historic Memorial Auditorium on the sense, the life of a researcher isn’t for Yamanaka: Dr Honjo puts it very well. I began my career as an orthopedic was excited by this unexpected med school campus. An excerpt follows. everyone. It’s not something you can You must enjoy what you are doing in surgeon, something I wanted to be from result. just stumble into. If you find yourself order to be a scientist. a young age. But I soon realized that I This experience galvanized my idea of Nowhere else in Asia can you find a Minato: In closing, we all have different asking “what should I do?” then that’s wasn’t very good at it, becoming a researcher; I simply followed single university with two Nobel reasons for being researchers, but what not the right mindset. so I tried my hand at the questions and results that interested laureates active among its research motivates you? What is your approach to To be a scientist, you need a constant research. me. I then went to the United States to faculty. Curious as to what might result devoting your life to science? drive of curiosity and the motivation to In one of my first study arteriosclerosis, but when the gene from a discussion between the two pursue the answers on your own. As experiments I had to I was focusing on was linked to cancer, I scientists — Dr Honjo and Shinya Honjo: Research has always been a joy children, everyone has the potential to test a drug that became fascinated with cancer research. Yamanaka, the director of the Center for for me; I can’t recall a moment when become anything. As you then grow up, would raise the Cancer then led me to stem cells. iPS Cell Research and Application, CiRA, I’ve suffered so much that I wanted to you learn your likes and limits, and a blood pressure of a I was always simply pursuing my and the 2012 Nobel laureate in stop doing it. vision of yourself takes shape. mouse. Surprisingly, curiosity. Dr Honjo and I have followed medicine — ExecVP/Provost Minato Nonetheless there comes a moment I chose the study of immunology. I the blood pressure different, but equally valid paths. The suggested that an open discussion would when anyone seeks deeper meaning wish you all the best as you seek to find fell! But what most common threads are that we both have be good for students, and a special event in life, whether to make money, or to what is your lifelong motivation. astonished me was immense curiosity and the motivation to was arranged for 27 December 2018 in pursue something for love. In that my own reaction: I try to find answers to the unexpected.

Kyoto U Research News 2019 Spring | 09 This second section features a sampling of some of the latest scholarship Cutting edge from KyotoU, covering a broad range of fields of inquiry from medical www.kyoto-u.ac.jp/cutting-edge/ science and robotics to sociology and economics.

New gears in your sleep clock

long-studied factor morning, around 3 am, and controlling human are thus unable to adjust to A sleep cycles actually standard cycles without has two forms, one that keeps undergoing treatment. a key protein stable and “FASPS is characterized by another that promotes its a mutation in the gene that degradation. codes for a protein essential From the heart and lungs for the circadian clock, called that propel our blood, to our Period 2, or PER2,” explains rumbling stomachs at lunch corresponding author Jean-Mi- time and feeling of tiredness in chel Fustin from KyotoU’s the evening, our bodies keep Graduate School of Pharma- steady rhythms day in and day ceutical Science. CK1D — but we couldn’t find CK1D2 — and the destroyer out. “The stability of the PER2 one that could stabilize it by Mr Hyde — CK1D1,” states This ‘circadian clock’ is a protein is a key factor in phosphorylating the serine that Fustin. “While in many cases series of tightly controlled determining how fast your is mutated in FASPS patients.” the same gene can code for cycles of specific amounts of circadian clock ticks.” Writing in PNAS, Fustin and different proteins, such a stark proteins that make us either In FASPS patients, PER2 is his collaborators explain that difference in function is rare.” sleepy or wakeful. It has unstable, resulting in a the stabilizing kinase was “Circadian clock mecha- recently attracted public sped-up clock. This is due to a within the Ck1d gene itself all nisms can be found in attention with the 2017 Nobel mutation that changes one along. Their findings show that bacteria, insects, plants, and Prize for Physiology or amino acid in the protein from in addition to destabilizing vertebrates. Understanding Medicine, but numerous a serine to a glycine. PER2, Ck1d has another form, these fundamental mecha- aspects of the clock’s functions “The stability of PER2 is one that does the exact nisms allows us to understand and how it regulates our regulated by the phosphoryla- opposite. our relationship with the health remain a mystery. tion of several critical amino While structurally very rhythmic environment,” One of the first circadian acids — a common way similar, these two kinase forms concludes co-corresponding rhythm sleep disorders to be proteins are regulated in the are named CK1D1 and author Hitoshi Okamura. “Our discovered was Familial body. This process is conduct- CK1D2. discoveries indicate that the Advanced Sleep Phase ed by other proteins called “The opposite activity of circadian clock can be was known about the animal’s genome. With this new data, koalas, and we were interested taste receptor gene catalog Syndrome, or FASPS. Patients kinases,” continues Fustin. CK1D2 was completely adjusted between these genome. With this study Takashi Hayakawa of KyotoU’s in how they perceive these enable koalas to optimize with this condition fall asleep “We knew of a kinase that unexpected. These two kinases, and provides new published in Nature Genetics, Primate Research Institute and leaves.” ingestion of nutrients and early in the evening, around 7 could destabilize PER2 — versions of this kinase can be targets for the treatment of the koala is now the fourth Don Colgan of the Australian After analyzing the genome, avoid plant toxins.” pm, and wake up early in the Casein kinase 1 delta, or likened to the kind Dr Jekyll — circadian disorders.” marsupial species to have its Museum analyzed the the duo found that koalas have Further analysis also showed genome sequenced, providing evolutionary background of more bitter taste receptor that koalas appear to have further understanding of the the koala’s taste receptor genes genes than any other Austra- functional receptors for both genetic background of its relating to its unique adapta- lian marsupial, and even more sweetness and umami biology, and establishing a tion to feed on eucalyptus. than most mammals. This perception, previously not high-quality genomic “Initial studies gave us enables the animals to detect observed in other animals with oalas have long including KyotoU — research- reference for marsupial insight into genes related to toxic metabolites contained in highly specialized diets. What does the captured people’s ers have successfully mammals. sensory receptors and detoxifi- eucalyptus, suggesting koalas “A complete genome K hearts and minds sequenced the entire koala The consortium sequenced cation enzymes, and I was can discriminate the toxicity sequence is the gold standard thanks to their cuddly features genome, uncovering much over 3.4 billion base pairs and curious about the koala’s levels of the leaves they ingest. in understanding any unique koala genome tell and seemingly relaxed that has been unknown about 26,000 genes in the koala palate,” explains Hayakawa. “Koalas have been shown to biological quality of an demeanor. these mesmerizing marsupials. “In all animals, including demonstrate selectivity in the animal,” concludes Hayakawa. Now, in a collaborative Past studies have revealed humans, ‘bitterness’ is usually leaves they consume, avoiding “Knowledge of the koala us about the taste study by the Koala Genome many unique features of the a warning sign indicating as much of a plant’s toxic genome is going to play a Consortium — involving 54 koala’s morphology, physiolo- toxicity. Eucalyptus leaves are metabolite as possible,” states pivotal role in the conservation of eucalyptus? scientists at 29 institutions, gy and ecology. However, little toxic to most animals including Hayakawa. “Expansions in the of these animals.”

10 | Kyoto U Research News 2019 Spring Search for article titles Cutting edge for paper, author details & more!

using a counseling dialogue corpus, resulting in dramati- Meet ERICA. cally improved engagement. Testing in five-minute She wants to listen to you sessions with a human subject, ERICA demonstrated e’ve all tried talking team demonstrated the when a listener asks for significantly more dynamic with devices, and in updates during a symposium elaboration, or repeats the speaking skills, including W some cases they talk at the National Museum of last word of the speaker’s backchanneling, partial back. But it’s a far cry from Emerging Science in Tokyo. sentence, allowing for more repeats, and statement having a conversation with a “When we talk to one engaging dialogue. assessments. real person. another, it’s never a simple Deploying a series of “Making a human-like Now a research team from back and forward progres- distance sensors, facial conversational robot is a Kyoto University, Osaka sion of information,” states recognition cameras, and major challenge,” states University, and the Tatsuya Kawahara of microphone arrays, the team Kawahara. “This project Advanced Telecommunica- KyotoU’s Graduate School of began collecting data on reveals how much complexi- tions Research Institute, or Informatics, an expert in parameters necessary for a ty there is in listening, which ATR, have significantly speech and audio process- fluid dialog between ERICA we might consider mundane. upgraded the interaction ing. and a human subject. We are getting closer to a system for conversational “Listening is active. We “We looked at three day where a robot can pass android ERICA, giving her express agreement by qualities when studying a Total Turing Test.” even greater dialogue skills. nodding or saying ‘uh-huh’ backchanneling,” continues ERICA is an android to maintain the momentum Kawahara. “These were: created by Hiroshi Ishiguro of conversation. This is timing — when a response of Osaka University and called ‘backchanneling’, and happens; lexical form — ATR, specifically designed is something we wanted to what is being said; and for natural conversation implement with ERICA.” prosody, or how the through incorporation of The team also focused on response happens.” human-like facial expressions developing a system for Responses were generated and gestures. The research ‘attentive listening’. This is through machine learning

was known about the animal’s genome. With this new data, koalas, and we were interested taste receptor gene catalog genome. With this study Takashi Hayakawa of KyotoU’s in how they perceive these enable koalas to optimize published in Nature Genetics, Primate Research Institute and leaves.” ingestion of nutrients and the koala is now the fourth Don Colgan of the Australian After analyzing the genome, avoid plant toxins.” marsupial species to have its Museum analyzed the the duo found that koalas have Further analysis also showed genome sequenced, providing evolutionary background of more bitter taste receptor that koalas appear to have further understanding of the the koala’s taste receptor genes genes than any other Austra- functional receptors for both genetic background of its relating to its unique adapta- lian marsupial, and even more sweetness and umami biology, and establishing a tion to feed on eucalyptus. than most mammals. This perception, previously not high-quality genomic “Initial studies gave us enables the animals to detect observed in other animals with oalas have long including KyotoU — research- reference for marsupial insight into genes related to toxic metabolites contained in highly specialized diets. captured people’s ers have successfully mammals. sensory receptors and detoxifi- eucalyptus, suggesting koalas “A complete genome hearts and minds sequenced the entire koala The consortium sequenced cation enzymes, and I was can discriminate the toxicity sequence is the gold standard thanks to their cuddly features genome, uncovering much over 3.4 billion base pairs and curious about the koala’s levels of the leaves they ingest. in understanding any unique and seemingly relaxed that has been unknown about 26,000 genes in the koala palate,” explains Hayakawa. “Koalas have been shown to biological quality of an demeanor. these mesmerizing marsupials. “In all animals, including demonstrate selectivity in the animal,” concludes Hayakawa. Now, in a collaborative Past studies have revealed humans, ‘bitterness’ is usually leaves they consume, avoiding “Knowledge of the koala study by the Koala Genome many unique features of the a warning sign indicating as much of a plant’s toxic genome is going to play a Consortium — involving 54 koala’s morphology, physiolo- toxicity. Eucalyptus leaves are metabolite as possible,” states pivotal role in the conservation scientists at 29 institutions, gy and ecology. However, little toxic to most animals including Hayakawa. “Expansions in the of these animals.”

Kyoto U Research News 2019 Spring | 11 Cutting edge

Partly as a result of multiculturalism, Japanese- Giant, recently Canadians are more likely to showcase their ethnicity extinct seabird also rather than to hide it. Accord- ing to Chiba Stearns, “As Canada becomes more inhabited Japan multicultural, what makes you unique — like your cientists report that a discovered in the 18th Japanese in Canada, ethnicity — is something you large, extinct seabird century on Bering Island, want to have stand out.” S called the spectacled was later hunted to with mixed feelings These records highlight the cormorant, Phalacrocorax extinction, following value of considering factors perspicillatus — originally colonization of the island in anada’s policies on ism due to past experiences such as immigrant identity, thought to be restricted to the early 1800s. multiculturalism are of incarceration during the voice, political conditions, Bering Island, far to the “Before our report, there C often seen as a model Second World War. social environments, and north — also resided in was no evidence that the for a more inclusive and Since the 1960s, political economy when Japan nearly 120,000 years cormorant lived outside of diverse world. They were Japanese-Canadians have assessing multiculturalism. ago. Bering Island,” explains first designed with the assumption been showcased as a ‘model Governments must tailor Writing in The Auk author Junya Watanabe of that multiculturalism is good minority’ due to their high policies to specific minority Ornithological Advances, the KyotoU’s Department of for minorities, and were levels of education, profes- groups along with state-level team indicates that the Geology and Mineralogy. therefore supported by these sional success, and English initiatives. species underwent a drastic Studying bird fossils groups. language proficiency. They De Souza says that these range contraction or shift, recovered from Shiriya, However, in a study have settled throughout results can help other and that specimens found on Aomori prefecture, published in the journal Canada, and have married countries that may need to Bering Island are ‘relicts’ — Watanabe and his team OMNES: The Journal of almost exclusively outside of embrace expanded immigra- remnants of a species that identified 13 bones of the Multicultural Society, their communities. tion in order to alleviate was once more widespread. spectacled cormorant from Japanese-Canadians show So why the ambivalence declining populations, such as The global threat of upper Pleistocene deposits, ambivalence to multicultural- towards multiculturalism? Japan. human activity to species formed nearly 120,000 years “Younger generations of “There is much to learn diversity is grave. To correct- ago. Japanese-Canadians are from the experience of ly assess human-related “It became clear that we supportive of it, but some Canada,” he concludes. extinction events, it is were seeing a cormorant affected the cormorant argue that it is only enacted in “Japan already has many imperative to study natural species much larger than any population. superficial ways,” explains minorities, so it is a mistake to distributions before first of the four native species in And prehistoric Japanese Lyle De Souza of KyotoU’s lump them all together as contact with humans. This is present-day Japan,” states may have hunted the species, Institute for Research in ‘non-Japanese’ and thereby where archaeological and co-author Hiroshige Matsuo- but archaeological evidence Humanities, who led the prevent their unique qualities fossil records play crucial ka. “At first we thought this of this has not yet come to study. from enriching the culture.” roles. might be a new species, but light. All told, the extinction “But there is lingering The spectacled cormorant, these fossils matched bones of the spectacled cormorant trauma from early racism and a large-bodied seabird first of the spectacled cormorant may be more complex than incarceration.” stored at the Smithsonian previously thought. To study how this trauma Institution.” “The cormorant was a distorts the effect of multicul- Changes in oceanograph- gigantic animal, its large size turalism on Japanese- standard microloans tend to be ic conditions may be thought to have been Canadians, De Souza spent geared toward business and responsible for the local achieved through adaptation several months in Canada entrepreneurial endeavors, in disappearance of the to the island-oriented conducting interviews with recent years Bangladesh has species in Japan. Paleocli- lifestyle on Bering,” adds academics, writers, and made a name for itself mate studies show that Watanabe. “But our finding Japanese-Canadians. internationally by providing oceanic food productivity suggests that this might not One well-known interview- n the developing sal. Formal financial institu- This is where ‘microfinance microcredits to tenant farmers. around Shiriya dropped have been the case; after all, ee featured in the study is world, access to tions are reluctant to lend to institutions’ — or MFIs — play Now, in a collaborative drastically in the Last it just resided there as a relict. animator and filmmaker Jeff credit can lead to households with low-in- a role. study with institutions in the Glacial Maximum, around The biological aspects of Chiba Stearns, whose works higher productivity and an comes or which lack MFIs extend small loans, United States and Bangladesh, 20,000 years ago. This these animals deserve much include the documentary increase in living standards, collateral. called microcredits, to a team led by Mohammad would have seriously more attention.” One Big Hapa Family. but this access is not univer- individual households. While Abdul Malek — of KyotoU’s

12 | Kyoto U Research News 2019 Spring

Graduate School of Agriculture increasing the credit access of crop income, and additionally and the Research and Evalua- tenant farmers to formal the probability of adopting tion Division of BRAC — has financial institutions,” explains hybrid and higher yield rice. examined the impact of Malek. “So we conducted two Further, there appeared to be a agricultural microcredits on surveys in 2012 and 2014 to somewhat positive effect on first to examine the impact of a the livelihood of these farmers. see how households receiving the cultivation of owned land program designed specifically Writing in the American this financing changed over and livestock ownership. to increase the financial Journal of Agricultural Econom- time.” “BCUP has had a number of inclusion — in the broader ics, the researchers analyzed The Bangladesh Bank — the positive effects,” continues economy — of tenant farmers. various outcomes of these central bank of Bangladesh — Malek. “We did not find a The team hopes to continue loans, such as: adoption of started BCUP with a low-inter- change in household income, their inquiry into the effects of high-yield or hybrid rice, est revolving fund, as part of its but we noticed that the microcredits in order to better overall rice yield, and house- financial inclusion strategy. farmers were able to allocate inform future policy decisions, hold income. The average loan amount was more time to self-employment while acknowledging that “The agricultural microcred- equal to the production cost of activities.” other interventions, in combi- it program Borgachashi rice for one hectare of land. While several studies have nation with microcredit, may Unnayan Prakalpa — The team’s results show that examined the role of agricul- be necessary if the program is BCUP — began in 2009 with BCUP helped increase rice tural credit on the livelihood of to be scaled up in Bangladesh the primary objective of yield as well as overall farm farm households, this is the or elsewhere in Asia. Search for article titles Cutting edge for paper, author details & more!

Partly as a result of multi- the experience is framed culturalism, Japanese- productively. In other words, Canadians are more likely to Finding success how failure is interpreted in showcase their ethnicity such conversations makes all rather than to hide it. Accord- through failure the difference. ing to Chiba Stearns, “As Manalo states that world- Canada becomes more earning from failure is attitudes and competencies wide, testing and test scores multicultural, what makes you a matter of common that support learning from are becoming more important unique — like your L folk wisdom. But in mistakes. to schools, teachers, and Japanese in Canada, ethnicity — is something you reality, most loath to fail, as “We put out an internation- students: to the extent that want to have stand out.” loss of motivation and al call for research pertaining they lose sight of the very with mixed feelings These records highlight the confidence — and perhaps to the benefits of failure,” purpose of education, which value of considering factors even lower standing among explains Manalo. “The 15 is to promote learning. anada’s policies on ism due to past experiences such as immigrant identity, peers — often result. In spite papers we selected represent “Failure is essential to multiculturalism are of incarceration during the voice, political conditions, of everything we know about the most robust research learning, but simply saying often seen as a model Second World War. social environments, and failure, we know very little clarifying what is necessary ‘we should learn from failure’ for a more inclusive and Since the 1960s, political economy when about its precise benefits. for failure to become benefi- or ‘ganbatte’ in Japanese is diverse world. They were Japanese-Canadians have assessing multiculturalism. Emmanuel Manalo at cial in an educational usually not enough,” designed with the assumption been showcased as a ‘model Governments must tailor KyotoU’s Graduate of context.” concludes Manalo. “We must that multiculturalism is good minority’ due to their high policies to specific minority Education and Manu Kapur at For instance, working in actively learn from the for minorities, and were levels of education, profes- groups along with state-level ETH Zurich in Switzerland collaboration with Yoshinori experience, and be aware of therefore supported by these sional success, and English initiatives. report that, while failure is Oyama from Chiba Universi- what to improve.” groups. language proficiency. They De Souza says that these essential to learning, instances ty, Manalo reveals in one Until students and educa- However, in a study have settled throughout results can help other where failure leads to benefi- study that people are more tors understand these published in the journal Canada, and have married countries that may need to cial outcomes and eventual motivated to continue conditions, failure will OMNES: The Journal of almost exclusively outside of embrace expanded immigra- success can be traced to working after failure if they continue to be feared and Multicultural Society, their communities. tion in order to alleviate particular circumstances. perceive themselves to be avoided, and people will Japanese-Canadians show So why the ambivalence declining populations, such as Their editorial, published in close to completion. More- hesitate due to fear of failing, ambivalence to multicultural- towards multiculturalism? Japan. a special issue of Thinking over, this motivation increases potentially resulting in missed “Younger generations of “There is much to learn Skills and Creativity, introduc- the more clearly the person opportunities for success. Japanese-Canadians are from the experience of es 15 research articles from sees how to complete the supportive of it, but some Canada,” he concludes. experts around the world task. argue that it is only enacted in “Japan already has many discussing the benefits of Meanwhile a team from superficial ways,” explains minorities, so it is a mistake to failure in a wide range of Ben-Gurion University in Lyle De Souza of KyotoU’s lump them all together as subjects, from mathematics to Israel shows that when Institute for Research in ‘non-Japanese’ and thereby science, and robotics to video teachers discuss their failures Humanities, who led the prevent their unique qualities gaming. Together these reveal with colleagues, they only study. from enriching the culture.” how it is possible to cultivate benefit from the discussion if “But there is lingering trauma from early racism and incarceration.” To study how this trauma distorts the effect of multiculturalism on Japanese- standard microloans tend to be Canadians, De Souza spent geared toward business and several months in Canada Using microcredit to increase entrepreneurial endeavors, in conducting interviews with recent years Bangladesh has academics, writers, and rice yield in Bangladesh made a name for itself Japanese-Canadians. internationally by providing One well-known interview- n the developing sal. Formal financial institu- This is where ‘microfinance microcredits to tenant farmers. ee featured in the study is world, access to tions are reluctant to lend to institutions’ — or MFIs — play Now, in a collaborative animator and filmmaker Jeff I credit can lead to households with low-in- a role. study with institutions in the Chiba Stearns, whose works higher productivity and an comes or which lack MFIs extend small loans, United States and Bangladesh, include the documentary increase in living standards, collateral. called microcredits, to a team led by Mohammad One Big Hapa Family. but this access is not univer- individual households. While Abdul Malek — of KyotoU’s

Kyoto U Research News 2019 Spring | 13

Graduate School of Agriculture increasing the credit access of crop income, and additionally and the Research and Evalua- tenant farmers to formal the probability of adopting tion Division of BRAC — has financial institutions,” explains hybrid and higher yield rice. examined the impact of Malek. “So we conducted two Further, there appeared to be a agricultural microcredits on surveys in 2012 and 2014 to somewhat positive effect on first to examine the impact of a the livelihood of these farmers. see how households receiving the cultivation of owned land program designed specifically Writing in the American this financing changed over and livestock ownership. to increase the financial Journal of Agricultural Econom- time.” “BCUP has had a number of inclusion — in the broader ics, the researchers analyzed The Bangladesh Bank — the positive effects,” continues economy — of tenant farmers. various outcomes of these central bank of Bangladesh — Malek. “We did not find a The team hopes to continue loans, such as: adoption of started BCUP with a low-inter- change in household income, their inquiry into the effects of high-yield or hybrid rice, est revolving fund, as part of its but we noticed that the microcredits in order to better overall rice yield, and house- financial inclusion strategy. farmers were able to allocate inform future policy decisions, hold income. The average loan amount was more time to self-employment while acknowledging that “The agricultural microcred- equal to the production cost of activities.” other interventions, in combi- it program Borgachashi rice for one hectare of land. While several studies have nation with microcredit, may Unnayan Prakalpa — The team’s results show that examined the role of agricul- be necessary if the program is BCUP — began in 2009 with BCUP helped increase rice tural credit on the livelihood of to be scaled up in Bangladesh the primary objective of yield as well as overall farm farm households, this is the or elsewhere in Asia. standard microloans tend to be geared toward business and entrepreneurial endeavors, in recent years Bangladesh has made a name for itself internationally by providing n the developing sal. Formal financial institu- This is where ‘microfinance microcredits to tenant farmers. world, access to tions are reluctant to lend to institutions’ — or MFIs — play Now, in a collaborative credit can lead to households with low-in- a role. study with institutions in the higher productivity and an comes or which lack MFIs extend small loans, United States and Bangladesh, increase in living standards, collateral. called microcredits, to a team led by Mohammad but this access is not univer- individual households. While Abdul Malek — of KyotoU’s

Cutting edge

simulation that calculates the Utilizing mouse ES cells in formation of three-dimensional culture, the team applied Making an eye for you tissue structures. Using this mechanical strain on specific knowledge and past experi- points and were pleased to f you want to build an have gained new understand- mental data, they constructed detect the calcium responses, organ, such as for ing of how cells undergoing a virtual precursor-eye and mechanical feedback, and cell I transplant, you need mechanical strain create the were able to predict the shape changes they had to think in 3D. spherical structure of the eye. physics driving the predicted in the simulations. For some time, scientists Publishing in Science sphere-forming cells. These findings reveal a new have used stem cells to grow Advances, the team has found Their findings show that role for mechanical forces in parts of organs in the lab, but that individual cells together during optic cup formation, a shaping organs, which is that is a far cry from construct- form a primordial, cup-like cell differentiation pattern — crucial in forming complex ing an actual, fully-formed, structure — an ‘optic cup’ — pushing cells into the cup tissues, even in a petri dish. functioning, three-dimensional by sensing mechanical forces shape — is generated, The team will continue to organ. resulting from the deformation causing a portion of the cells investigate these forces, For students of regenerative of the entire tissue. to spontaneously fold into seeking to advance the field of medicine and developmental “In the past, we succeeded the tissue. This force caused regenerative medicine. biology, this is why under- in making the optic cup by by ‘self-bending’ propagates “While our research shows standing how cells bend and culturing embryonic stem — to the boundary region, the possibility of controlling move to form organs and ES — cells. To form a sphere, where other cells sense the the shapes of organs made in bodily tissue is a hot topic. the tissue first needed to strain. vitro — using appropriate And now a team at protrude from primordial brain “The combination of the mechanical stimulation based KyotoU’s Institute for Frontier tissue and then invaginate tissue deformation and the on prediction — current Life and Medical Sciences inside,” explains first author strain on the boundary of the techniques are still limited,” Satoru Okuda. optic cup generates a hinge concludes lead scientist “But how individual that further pushes the Mototsugu Eiraku. cells sensed and bending cells,” continues “We hope to improve the modulated themselves Okuda, “leading to the predictive accuracy of our to form that shape had cup-like structure.” simulations and recreate more been unclear.” “The next step was to verify complicated tissues and The team devel- this prediction using actual ES organs in the future.” oped a computational cells.”

14 | Kyoto U Research News 2019 Spring standard microloans tend to be geared toward business and entrepreneurial endeavors, in recent years Bangladesh has made a name for itself internationally by providing n the developing sal. Formal financial institu- This is where ‘microfinance microcredits to tenant farmers. world, access to tions are reluctant to lend to institutions’ — or MFIs — play Now, in a collaborative credit can lead to households with low-in- a role. study with institutions in the higher productivity and an comes or which lack MFIs extend small loans, United States and Bangladesh, increase in living standards, collateral. called microcredits, to a team led by Mohammad but this access is not univer- individual households. While Abdul Malek — of KyotoU’s

Kyoto University spans three campuses in the city of Kyoto, numerous offices, research facilities, and other operations around the country, and KyotoU today dozens of centers, liaison offices, and field stations across the globe. In this Graduate School of Agriculture increasing the credit access of crop income, and additionally third section, learn of some of the latest developments from industry and the Research and Evalua- tenant farmers to formal the probability of adopting outreach, overseas offices, and student life. tion Division of BRAC — has financial institutions,” explains hybrid and higher yield rice. examined the impact of Malek. “So we conducted two Further, there appeared to be a agricultural microcredits on surveys in 2012 and 2014 to somewhat positive effect on first to examine the impact of a the livelihood of these farmers. see how households receiving the cultivation of owned land program designed specifically Writing in the American this financing changed over and livestock ownership. to increase the financial Journal of Agricultural Econom- time.” “BCUP has had a number of inclusion — in the broader Science with industry: ics, the researchers analyzed The Bangladesh Bank — the positive effects,” continues economy — of tenant farmers. various outcomes of these central bank of Bangladesh — Malek. “We did not find a The team hopes to continue Microbes are us. But how can we see them? loans, such as: adoption of started BCUP with a low-inter- change in household income, their inquiry into the effects of high-yield or hybrid rice, est revolving fund, as part of its but we noticed that the microcredits in order to better “And this is the DNA “We’re collaborating with overall rice yield, and house- financial inclusion strategy. farmers were able to allocate inform future policy decisions, sequencer.” government, academia, and hold income. The average loan amount was more time to self-employment while acknowledging that Fumito Maruyama, industry in Japan and Chile. “The agricultural microcred- equal to the production cost of activities.” other interventions, in combi- smiling infectiously, pulls Together we’ve founded the it program Borgachashi rice for one hectare of land. While several studies have nation with microcredit, may out a device the size of a MACH — Monitoring of Unnayan Prakalpa — The team’s results show that examined the role of agricul- be necessary if the program is flip phone and begins to Algae in Chile — project, BCUP — began in 2009 with BCUP helped increase rice tural credit on the livelihood of to be scaled up in Bangladesh explain how it can help us supported by SATREPS, to the primary objective of yield as well as overall farm farm households, this is the or elsewhere in Asia. ‘see’ the world of microbes. understand the microbio- “We’ve come a long way logical basis of algal since the days when blooms, which have a plagues and disease were detrimental impact on interpreted as acts of commercial salmon farm- heavenly wrath. But there is ing.” still so much to learn.” Together with Japanese The palm-sized, chemical manufacturer USB-powered DNA Kaneka Corp, Maruyama sequencer is a key part of has developed the suitcase Maruyama’s suitcase lab, lab to allow anybody to an innocuous-looking analyze DNA in water rolling bag housing all the samples in the field. These equipment a microbiologist data form a snapshot of the needs for genetic sampling microorganisms in the bacteria, we gain a deeper civilization, but we’ve only and analysis in the field. We water: a vital step in understanding of how these just now begun to under- were lucky to catch him just predicting and even fragile ecosystems stay in or stand them. Biosphere 2 ran as he was about to embark mitigating dangerous algae. fall out of balance.” into problems because the on another trip to the “By looking at the whole Beyond MACH, designers only had the Pacific coast of South biome — ‘holobiome’ — of Maruyama looks to a future human environment in America. algal blooms and mapping for the suitcase lab as a tool mind.” the dynamics of viruses and for citizen science or for With talks of colonizing teaching about the vast, Mars and living in space microbiological world. He coming ever closer to sees applications in indus- reality, Maruyama says the tries such as agriculture and time is ripe to study the forestry, and after speaking microbiology and ecology with him it’s hard to that sustain us. Our survival imagine what isn’t affected hinges not on maintaining by microbes. ‘cleanliness’, but rather in “Humanity has been determining how we must dealing with microbes since stay in balance with this far before the advent of unseen environment.

For more on MACH see: www.mach-satreps.org/en/

Kyoto U Research News 2019 Spring | 15 KyotoU today

News from overseas centers

North American Center opens in Washington DC 2200 Pennsylvania Avenue NW • Room 4057, 4th Floor East • Washington DC 20337 USA

In October 2018, Kyoto International Strategy University established its Office, and a KyotoU North American Center to alumnus. promote and deepen The University has six educational and research institutional-level student ties with universities and exchange agreements with research institutions in the American universities and Americas. also six in Canada. With Located in central this new presence on the Washington DC, the office East Coast, the Center seeks will work to enhance the to facilitate the mobility of University’s contribution to students between Japan and knowledge-creation, North America, including technical innovation, and the development of summer intellectual openness for the courses and short-term betterment of global programs to increase society. early-exposure opportuni- research engagement York City, receiving a warm “A physical presence in ties for students on both across North America. welcome from East Washington is another sides of the Pacific. Director Badenoch is an Coast-based graduates. And critical step in the interna- Existing research East Coast native, who has initial contacts with tionalization of Kyoto projects and institutional since spent more than 15 research and educational University, representing a development underway in years in Japan and another partners in the region commitment to enhancing faculties and centers eight in Southeast Asia. indicate high hopes for partnerships with institu- across the University will After his 2006 PhD at KyotoU’s new presence. tions of academic also be supported, based KyotoU in Asian and Now with three Centers excellence in North Ameri- in part on existing MoUs, African studies, he worked worldwide, the University ca,” explains Nathan providing a solid and in Thailand and Laos before has a better ability than Badenoch, Center director, dynamic foundation from returning to Kyoto as a ever to coordinate its global faculty member at the which to expand KyotoU’s member of the first class of activities, collaborations, Hakubi scholars in 2010. exchanges, and knowl- After this he began teach- edge-creation. ing, while continuing The North American research at the Center for Center is supported by the Southeast Asian Studies. North American team at the Now this new position has International Strategy Office brought him back to the in Kyoto, as well as by United States to assist in Kyoto University staff expanding KyotoU’s global seconded to Halcyon in presence. Washington under the The Center has already University’s John Mung Director Badenoch (rear, second from left) organized alumni gatherings Program. with East Coast KyotoU alumni in Washington and New

16 | Kyoto U Research News 2019 Spring KyotoU today

Bangkok ASEAN Center www.oc.kyoto-u.ac.jp/overseas-centers/asean/en/

KyotoU’s ASEAN Center researchers affirmed the received official foreign significance attached to NGO status from the Thai this achievement. At the Ministry of Labour in same event, KyotoU March 2018, as a result of concluded a MoU with Student mobility is a key Growing forces of sustained efforts by Direc- Thailand’s National Science factor in ensuring that this regionalization such as the tor Mamoru Shibayama and Technology Develop- momentum accelerates. ASEAN Economic Commu- and Center staff, with ment Agency, Approximately 180 nity increasingly require the continuous support from demonstrating the collabo- students from KyotoU are next generation of scientists regional partners. This rative synergies that are currently studying in to cooperate in finding approval was a landmark being accelerated by the Thailand, while 60 Thai common ground within achievement not only for ASEAN Center. students come to Kyoto their heterogeneous Kyoto University, but also The new NGO status annually. The University perspectives. Expectations for Japanese academia reflects the commitment on has developed double-de- are high that the Center’s more broadly in Thailand the part of representatives gree programs with the new status will increase the and the ASEAN region: the from both countries toward universities of Chulalong- exchange of students and first of its kind bestowed strengthening Japan-ASEAN korn, Kasetsart, and researchers between upon a Japanese university. collaboration in education Mahidol, and established KyotoU and its partners in At a commemorative and research, with the on-site laboratories in the Thailand and throughout ceremony in Bangkok on Center playing a central Vidyasirimedhi Institute of ASEAN, increasing the 28 September, the atten- role in catalyzing these Science and Technology reach of mutually beneficial dance of 100 officials and connections. and at Mahidol University. Japan-ASEAN collaboration.

Heidelberg European Center www.oc.kyoto-u.ac.jp/overseas-centers/eu/en/

As part of its mission to between 2014–2018 in facilitate intellectual order to deepen intellectual exchange on significant partnerships and foster social and scientific issues, collaborations by sharing KyotoU’s European Center the strengths of each has supported the planning university. climate, and digital transfor- follow-through on such and organizing of joint KyotoU hosted the 2nd mation in logistics. symposia and workshops, symposia with four univer- KyotoU-Universität Ham- In 2019, international exploring and designing sities in Sweden (Stockholm burg Symposium, 9–11 workshops with Vienna future research collabora- University, Uppsala Univer- October 2018, showcasing University and Zurich tion through continual sity, KTH Royal Institute of joint projects in law, University are planned to close communication with Technology, and Karolinska sociology, and manage- further develop regional counterpart universities, Institutet), as well as with ment begun at the 2017 relations and encourage fulfilling its role as a pivotal Bordeaux, Bristol-Heidel- meeting in Hamburg, as reciprocity with these hub between Kyoto Univer- berg, UCL, Zurich, and well as new cooperation in universities. sity and partner institutions Hamburg. A series of these ecological research, The European Center’s throughout Europe. meetings took place development studies, location facilitates KyotoU’s

Kyoto U Research News 2019 Spring | 17 Student voices omotenashi

Tea and the taste of A mizusashi (water vessel) by Dr Hisamatsu, featuring the Shinchakai ‘spirit of tea’ club sadoshin — way of tea — that he taught the first club members (4th Year, Faculty of Integrated Human Studies) Rika Yokoi

“With tea ceremony, learning the move- matters is your spirit of hospitality — ments is just the beginning. You then start to omotenashi.” pay attention to the smallest of details, such Using a tea bowl acquired by Dr These words gained special meaning for Hisamatsu to commemorate the as the exact placement of your hands and Rika in her third year, when she was club’s 20th anniversary whether your breathing is in tune with that responsible for organizing a ceremony of of your guest.” Rika Yokoi’s first experience gratitude by younger students for graduating with tea ceremony was in a high school seniors. Club alumni were also invited. She club, and when she enrolled at Kyoto worked very hard on the choice of temple University she joined the Shinchakai. venue and on assigning roles to everyone. Rika pays particular attention to timing. When the ceremony was over, a thank you “After serving the guest a confection, I pace note from an alumni guest left an indelible the tea preparation to match when the guest impression on Rika’s heart. It included a will finish eating. If the guest needs more tanka: “A lovely, youthful ceremony, full of time, I slow down.” freshness.” At the behest of students, assistant professor “Sending a thank you letter is a matter of of philosophy Shinichi Hisamatsu founded etiquette, but to also write such a heartfelt Shinchakai in 1941 with help from Urasen- poem is wonderful and really moved me. I ke master Tantansai. was so nervous that day and I’m sure I made Sadô — Japanese tea ceremony — originat- many mistakes, but in spite of this, the ed from practice of Zen Buddhism. alumni were watching over me with real Shinchakai is infused with the Zen thinking warmth.” of Dr Hisamatsu, including conducting Zen “I hope to continue until I graduate.” Rika is meditation before and after each tea currently in her fourth year at the Faculty of practice. Integrated Human Studies. “Even if I can’t Rika finds one Hisamatsu episode — related always be perfect in my club activities and to her by a club alumna — to be unforgetta- studies, I want to complete them properly.” ble. One day a student asked the professor Her major is Christian art history. In her how they could afford the cost of the quest to master the ‘way of tea’, Rika shows confections and tea for an upcoming boundless curiosity, and in her four years ceremony. Hisamatsu replied: “For the with Shinchakai her heart has filled to confection, go to nearby Mt Yoshida and overflowing with the feelings of the many pick up some chestnuts. And if the tea’s too people she has encountered and connected expensive, just serve hot water. What with through her spirit of omotenashi.

Club members intensely critique each other during practice, from the positions of their fingers to the tempo of their movements

18 | Kyoto U Research News 2019 Spring Eternal aesthetic

Artwork by Kyoto University students, combined A Fund to with artistic scenes as glimpsed by researchers. help us grow 雪尋理子「雪尋「い理子「どや雪尋そし「綺麗たっ「のかだ」ったよ。 Since its founding in 1897, Kyoto 喜んでる見せてあげたいぐらい」ん…… だけど University has been committed to a

…… 星、綺麗だった？」 spirit of openness and academic …… freedom that pervades all levels of ごめん。嬉しいんだけど（泣いている）」 academic life, from freshman courses to research in world-leading …… laboratories. …… 雪尋くんにも、 Protecting and promoting this 」 freedom, and encouraging students to reach even further, is the highest goal of the institution. …… The Kyoto University Fund provides an avenue for university stakeholders — from members of the local community to businesses and corporate sponsors — to support these students, their efforts, and their learning and study environment. In addition to a main, central fund, special-purpose funds are targeted Videographer: toward particular activities and fields Butterfly Studies Club of research. Taisuke Nomura (2nd Year Master’s, Graduate School of Agriculture) One example is the SPEC (Student Projects for Enhancing Creativity) Gentle tranquility and nostalgia exude from fund, in which student r&d projects the foregoing works. In mid-May, the selected through a contest received Japanese Clouded Apollo butterfly begins to development funding. Yukihiro : The stars… were they beautiful? dance in the backwoods of Sakyo-ku, on the outskirts of Kyoto. Looking at these Making dreams a reality for Riko : Yes, they were. So beautiful that butterflies, flittering about the uplands students and researchers throughout I wish I could have shown them which are largely unchanged for centuries, I the institution: this is what the Fund to you. feel curiously calm. I wish to protect Japan’s makes possible. traditional landscapes for all time. Yukihiro : I see… (cries) For details on types and levels of support, as well as payment Riko : What’s the matter? methods, please see the website Yukihiro : It’s nothing. Sorry. I’m happy… below. Your generous support of the university is most greatly I really am, but… appreciated. Keppeki Theater Troupe Koshi Takaya (4th Year, Faculty of Letters) Kyoto University Fund Excerpt from: Siblings Enraptured +81 75-753-2210 A man and a woman are reunited at the en.kikin.kyoto-u.ac.jp boundary of life and death. Their words spring forth from the contradictions between meeting and parting, joy and sadness, dreams and reality. The nostalgic strains of the music, Shun Fujii (2nd Year Master’s, Graduate with hints of enjoyment and lament, School of Engineering) occasionally cherishing a life filled with Title: Cinema Paradiso medley contradictions, reminded me of this scene. Composer: Ennio Morricone When I first got interested in the saxophone, I listened to many sax CDs. One in particular, featuring the enduringly popular Italian film Cinema Paradiso, captivated me with its hauntingly beautiful, nostalgic melodies.

Kyoto U Research News 2019 Spring | 19 facebook.com/Kyoto.Univ.E

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