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| Making the first challenge in the world many times?Horiuchi’s quest started when he was assigned a relatively unique research theme. |
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Professor Horiuchi belongs to the Laboratory of Immunobiology, which was formerly called the “Laboratory of Animal Hygiene,” and has mainly conducted research on chicken diseases and the immune system. Horiuchi proceeded to the graduate school expecting to undertake related studies, when he was assigned a seemingly irrelevant research theme.
“In those days, growth factors were drawing increasing attention, and it was assumed that chickens also had growth factors. I was encouraged to undertake research into chicken growth factors.” Starting with this suggestion, Horiuchi has made extremely innovative challenges ahead of the world. A few examples are participation in the development of methods for producing antibodies using chickens, and the discovery that a large number of growth factors and adhesion factors are retained in chicken thrombocytes (avian platelets). Horiuchi was “continuously engaged in such research activities” during his youth. Subsequently, he proceeded to take on molecular and cellular biosciences, where he was able to contribute to avian immunology as one of the laboratory specialties through his experience. An example of this process was as follows. |
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While interleukins (ILs) are substances that have extremely important functions in the immune system, the analysis of avian ILs had lagged behind. After developing the technology to produce chicken antibodies, Horiuchi’s laboratory decided to analyze ILs that could be applied to this technology. “When we just decided to undertake molecular biological and/or biochemical analysis targeted at IL6, a paper was published stating that ES cells had been established from chicken embryos.”
This paper pertained to ES cells (embryonic stem cells), which had not been collected from birds before, while ES cell manipulation technology had been established for mice in 1980s. Professor Horiuchi and his team felt a strong sense of inconsistency concerning this paper. |
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“In the culturing of ES cells, a protein called “LIF” plays an important role. In this paper, mouse LIF protein was used.”
Professor Horiuchi had proceeded to research into IL from chicken cell growth factors, and therefore knew that mice and chicken had ILs with substantially different amino acid compositions. Because both IL6 and LIF can be traced back to the same gene, Horiuchi analyzed these two at the same time, and later succeeded in the cloning of LIF. This research was promoted through industry-academia-government cooperation under the Hiroshima Prefectural government, and was selected as one of the intelligent cluster projects organized by the Ministry of Education, Culture, Sports, Science and Technology. |
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| Centered on gene recombination and genome editing, his research contributes to the fight against diseases. |
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In Horiuchi’s own words, his team “substantially shifted the focus of their research to these fields in around 2000.” What would their achievements lead to? Because stem cells can be differentiated into diverse cells, it is possible to produce “genetically modified chickens.” For example, research activities have been promoted to reduce allergens in eggs, to incorporate an influenza-resistant gene into chickens, and so on. Once these trials turn out successful, some of the problems that plague today’s world could be resolved.
As the focus of his present research, Horiuchi applies two technologies?gene recombination technology and genome editing technology?to ES cells and other stem cells, placing greater weight on the latter. |
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“We are promoting Hiroshima University as a base for genome editing in Japan, under the leadership of Professor Takashi Yamamoto at the School of Science. As one of the members, I seek to generate genome-edited chickens,” says Horiuchi. This research has been selected for the Program on Open Innovation Platform with Enterprises, Research Institute and Academia (OPERA), organized by the Japan Science and Technology Agency.
In terms of gene recombination technology, Professor Horiuchi’s team is investigating the avian defense mechanism against influenza. “When avian flu spreads in Japan, the flu strain that has spread in South Korea is also brought into Japan. Surveys have been conducted assuming that wild birds bring the flu into Japan. When chickens are infected by such flus, they usually die within 48 hours. On the other hand, some migratory birds do not die from avian influenza. Isn’t this interesting? This is because wild ducks and other aquatic birds are called ‘natural hosts,’ and are resistant to influenza,” explains Horiuchi. |
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It has been known that a certain gene is related to this phenomenon. What if, then, this gene is incorporated into chickens? This is the aim of his research concerning the development of a chicken model for a host response to influenza, on consignment from the Ministry of Agriculture, Forestry and Fisheries. Professor Horiuchi is seeking to leverage both genome editing technology and gene recombination technology for the “breed improvement of chickens in the future.”
Another challenge that Horiuchi is taking on is research into prion diseases, in particular Creutzfeldt-Jakob Disease (CJD).
Before Bovine Spongiform Encephalopathy (BSE) became an issue in Japan, Horiuchi’s laboratory had started producing chicken antibodies, highlighting prion proteins. Horiuchi inherited this research from his predecessor. |
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“While common antibodies are produced from mice and rabbits, it is difficult to collect preferable antibodies for prion proteins from mammals, probably due to their high affinity. Better antibodies can be produced using chickens.”
In addition, Horiuchi remarks, “In Japan, one out of a million people develops this disease in a year for unknown causes. CJD sometimes develop spontaneously through aging. It is frightening that patients usually die within two years from the onset.” He hopes to enable the diagnosis of this prion disease at the earliest stage possible, leveraging the characteristics of chicken antibodies. |
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| Attitude toward research bearing the application and subsequent stages in mind |
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Professor Horiuchi is from Fukuoka Prefecture. He was born to a family that kept various animals, and one of his older brothers wanted to become a veterinarian. “I must have been influenced by my brother. I was also interested in environmental conservation, because Minamata disease and other pollutions were major issues when I was a child,” remarks Horiuchi, looking back on his childhood.
Horiuchi says that other things that affected him included books titled Torrent of Biological Sciences and Torrent of Biological Sciences: Sequel. In these books, noted researchers representing Japan state their philosophies and other thoughts. One of these researchers, Professor Goro Eguchi, became a mentor to Horiuchi, when he studied at the National Institute for Basic Biology, using a domestic study-exchange program just after becoming an assistant. “During those days, I made the acquaintance of many researchers. My experience at this Institute plays the largest role in my present research,” comments Horiuchi. In Horiuchi’s room, quotes from Professor Eguchi are still posted.
When asked about the best part of his job, Horiuchi answered, “the greatest fun is when our hypothesis is proven through experiments.” As for his future goal, Horiuchi immediately responded that he wanted to present his research achievements in a manner that would contribute to society. “This has always been my goal. While we definitely recognize the importance of basic research, we are undertaking research activities in an agriculture-based faculty, in a field close to application. Therefore, we would like to continue our research bearing this in mind.” ‘Basic research’, ‘parts that could be linked to application,’ and ‘preparations required when research achievements are applied in society’?these three aspects are promoted simultaneously in Horiuchi’s research diagram.
Horiuchi is also proud of the high quality of the research environment and learning opportunities in his laboratory, saying, “mine is the only laboratory in Higashihiroshima City that has its own proprietary genetic nucleotide sequencer.”
He encourages young people, saying, “In my laboratory, many undergraduates and graduates are engaged in studies and research activities. Most of them are earnest and performing well, and have established favorable relationship among themselves. If you are interested in chickens, the immune system, or genome editing, why not drop in on us? If you like our laboratory, join us and participate in our research.” |
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| Hiroyuki Horiuchi |
| Professor, Laboratory of Immunobiology
January 1, 1992-March 31, 2002 Assistant, School of Integrated Arts and Sciences and School of Applied Biological Science, Hiroshima University
April 1, 2007-March 31, 2010 Assistant Professor, School of Applied Biological Science, Hiroshima University
April 1, 2010-April 30, 2012 Associate Professor, School of Applied Biological Science, Hiroshima University
May 1, 2012-present Professor, School of Applied Biological Science, Hiroshima University
Posted on Aug 4, 2017 |
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