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Shoichiro Kurata

Section

Graduate School of Pharmaceutical Sciences

Job title

Professor

Degree

薬学博士（東京大学）
薬学修士（山形大学）

researchmap

https://researchmap.jp/read0007729

J-GLOBAL ID

200901054331079821

Research History 4

1998/03 - Present

Graduate School of Pharmaceutical Sciences, Tohoku University
1995/04 - 1998/03

Postdoctoral research fellow, Swiss National Science Foundation
1991/04 - 1998/03

University of Tokyo, Assistant Professor
1990/04 - 1991/03

Postdoctoral research fellow, Fellowships of the Japan Society for the Promotion of Science for Japanese Junior Scientists.

Education 2

The University of Tokyo　Graduate School, Division of Pharmaceutical Sciences　生命薬学

- 1990/03/29
Yamagata University　Faculty of Science　生物学科

- 1985/03/31

Professional Memberships 6

日本発生生物学会
日本生体防御学会
日本比較免疫学会
日本薬学会
日本分子生物学会
日本生化学会

︎Show all ︎Show first 5

Research Interests 5

peptidoglycan
transdetermination
pathogen recognition
organ identity
innate immunity

Research Areas 4

Life sciences / Molecular biology / Molecular Biology
Life sciences / Developmental biology /
Life sciences / Pharmacology /
Life sciences / Pharmaceuticals - health and biochemistry /

Papers 167

Neural control of redox response and microbiota-triggered inflammation in Drosophila gut

Naoyuki Fuse, Haruka Hashiba, Kentaro Ishibashi, Takuro Suzuki, Quang-Dat Nguyen, Kiho Fujii, Wakako Ikeda-Ohtsubo, Haruki Kitazawa, Hiromu Tanimoto, Shoichiro Kurata

Frontiers in Immunology　14　2023/10/26
Publisher: Frontiers Media SA
DOI： 10.3389/fimmu.2023.1268611 　

eISSN： 1664-3224

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Background The neural system plays a critical role in controlling gut immunity, and the gut microbiota contributes to this process. However, the roles and mechanisms of gut-brain-microbiota interactions remain unclear. To address this issue, we employed Drosophila as a model organism. We have previously shown that NP3253 neurons, which are connected to the brain and gut, are essential for resistance to oral bacterial infections. Here, we aimed to investigate the role of NP3253 neurons in the regulation of gut immunity. Methods We performed RNA-seq analysis of the adult Drosophila gut after genetically inactivating the NP3253 neurons. Flies were reared under oral bacterial infection and normal feeding conditions. In addition, we prepared samples under germ-free conditions to evaluate the role of the microbiota in gut gene expression. We knocked down the genes regulated by NP3253 neurons and examined their susceptibility to oral bacterial infections. Results We found that immune-related gene expression was upregulated in NP3253 neuron-inactivated flies compared to the control. However, this upregulation was abolished in axenic flies, suggesting that the immune response was abnormally activated by the microbiota in NP3253 neuron-inactivated flies. In addition, redox-related gene expression was downregulated in NP3253 neuron-inactivated flies, and this downregulation was also observed in axenic flies. Certain redox-related genes were required for resistance to oral bacterial infections, suggesting that NP3253 neurons regulate the redox responses for gut immunity in a microbiota-independent manner. Conclusion These results show that NP3253 neurons regulate the appropriate gene expression patterns in the gut and contribute to maintain homeostasis during oral infections.
Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation International-journal International-coauthorship Peer-reviewed

Stefania Dentice Maidana, Mariano Elean, Kohtaro Fukuyama, Yoshiya Imamura, Leonardo Albarracín, Sudeb Saha, Yoshihito Suda, Shoichiro Kurata, María Ángela Jure, Haruki Kitazawa, Julio Villena

International Journal of Molecular Sciences　24:8804　1-16　2023/05/15
Publisher: MDPI
DOI： 10.3390/ijms24108804 　

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IF = 6.208
Oral Administration of Lacticaseibacillus rhamnosus CRL1505 Modulates Lung Innate Immune Response against Klebsiella pneumoniae ST25. International-journal International-coauthorship Peer-reviewed

Stefania Dentice Maidana, Yoshiya Imamura, Mariano Elean, Leonardo Albarracín, Keita Nishiyama, Yoshihito Suda, Shoichiro Kurata, María Ángela Jure, Haruki Kitazawa, Julio Villena

Microorganisms　11:1148　(5)　1-13　2023/04/28
Publisher:
DOI： 10.3390/microorganisms11051148 　

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Orally administered Lacticaseibacillus rhamnosus CRL1505 enhances respiratory immunity, providing protection against respiratory viruses and Streptococcus pneumoniae. However, the capacity of the CRL1505 strain to improve respiratory immunity against Gram-negative bacterial infections has not been evaluated before. The aim of this work was to evaluate whether the Lcb. rhamnosus CRL1505 was able to beneficially regulate the respiratory innate immune response and enhance the resistance to hypermucoviscous KPC-2-producing Klebsiella pneumoniae of the sequence type 25 (ST25). BALB/c mice were treated with the CRL1505 strain via the oral route and then nasally challenged with K. pneumoniae ST25 strains LABACER 01 or LABACER 27. Bacterial cell counts, lung injuries and the respiratory and systemic innate immune responses were evaluated after the bacterial infection. The results showed that K. pneumoniae ST25 strains increased the levels of TNF-α, IL-1β, IL-6, IFN-γ, IL-17, KC and MPC-1 in the respiratory tract and blood, as well as the numbers of BAL neutrophils and macrophages. Mice treated with Lcb. rhamnosus CRL1505 had significantly lower K. pneumoniae counts in their lungs, as well as reduced levels of inflammatory cells, cytokines and chemokines in the respiratory tract and blood when compared to infected controls. Furthermore, higher levels of the regulatory cytokines IL-10 and IL-27 were found in the respiratory tract and blood of CRL1505-treated mice than controls. These results suggest that the ability of Lcb. rhamnosus CRL1505 to help with the control of detrimental inflammation in lungs during K. pneumoniae infection would be a key feature to improve the resistance to this pathogen. Although further mechanistic studies are necessary, Lcb. rhamnosus CRL1505 can be proposed as a candidate to improve patients' protection against hypermucoviscous KPC-2-producing strains belonging to the ST25, which is endemic in the hospitals of our region.
The Ability of Postimmunobiotics from L. rhamnosus CRL1505 to Protect against Respiratory Syncytial Virus and Pneumococcal Super-Infection Is a Strain-Dependent Characteristic International-journal International-coauthorship Peer-reviewed

Fernanda Raya-Tonetti, Patricia Clua, Kohtaro Fukuyama, Guillermo Marcial, Jacinto Sacur, Gabriela Marranzino, Mikado Tomokiyo, Guadalupe Vizoso-Pinto, Apolinaria García, Shoichiro Kurata, Haruki Kitazawa, Julio Villena

Microorganisms　10:2185　1-22　2022/11/03
Publisher:
DOI： 10.3390/microorganisms10112185 　
Transcriptome features of innate immune memory in Drosophila

Naoyuki Fuse, Chisaki Okamori, Ryoma Okaji, Chang Tang, Kikuko Hirai, Shoichiro Kurata

PLOS Genetics　18　(10)　e1010005-e1010005　2022/10/17
Publisher: Public Library of Science (PLoS)
DOI： 10.1371/journal.pgen.1010005 　

eISSN： 1553-7404

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Immune memory is the ability of organisms to elicit potentiated immune responses at secondary infection. Current studies have revealed that similar to adaptive immunity, innate immunity exhibits memory characteristics (called "innate immune memory"). Although epigenetic reprogramming plays an important role in innate immune memory, the underlying mechanisms have not been elucidated, especially at the individual level. Here, we established experimental systems for detecting innate immune memory in Drosophila melanogaster. Training infection with low-pathogenic bacteria enhanced the survival rate of the flies at subsequent challenge infection with high-pathogenic bacteria. Among low-pathogenic bacteria, Micrococcus luteus (Ml) and Salmonella typhimurium (St) exerted apparent training effects in the fly but exhibited different mechanisms of action. Ml exerted training effects even after its clearance from flies, while live St persisted in the flies for a prolonged duration. RNA sequencing (RNA-Seq) analysis revealed that Ml training enhanced the expression of the immune-related genes under the challenge condition but not under the non-challenge condition. In contrast, St training upregulated the expression of the immune-related genes independent of challenge. These results suggest that training effects with Ml and St are due to memory and persistence of immune responses, respectively. Furthermore, we searched for the gene involved in immune memory, and identified a candidate gene, Ada2b, which encodes a component of the histone modification complex. The Ada2b mutant suppressed Ml training effects on survival and disrupted the expression of some genes under the training + challenge condition. These results suggest that the gene expression regulated by Ada2b may contribute to innate immune memory in Drosophila.
Respiratory Commensal Bacteria Increase Protection against Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Infection International-journal International-coauthorship Peer-reviewed

Stefania Dentice Maidana, Ramiro Ortiz Moyano, Juan Vargas, Kohtaro Fukuyama, Shoichiro Kurata, Vyacheslav Melnikov, María Jure, Haruki Kitazawa, Julio Villena

Pathogens　11　(1063)　1-11　2022/09/19
Publisher: MDPI
DOI： 10.3390/pathogens11091063 　

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IF = 4.531
Genetic dissection of innate immune memory in Drosophila melanogaster

Chang Tang, Shoichiro Kurata, Naoyuki Fuse

Frontiers in Immunology　13　2022/08/04
Publisher: Frontiers Media SA
DOI： 10.3389/fimmu.2022.857707 　

eISSN： 1664-3224

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Current studies have demonstrated that innate immunity possesses memory characteristics. Although the molecular mechanisms underlying innate immune memory have been addressed by numerous studies, genetic variations in innate immune memory and the associated genes remain unclear. Here, we explored innate immune memory in 163 lines of Drosophila melanogaster from the Drosophila Synthetic Population Resource. In our assay system, prior training with low pathogenic bacteria (Micrococcus luteus) increased the survival rate of flies after subsequent challenge with highly pathogenic bacteria (Staphylococcus aureus). This positive training effect was observed in most lines, but some lines exhibited negative training effects. Survival rates under training and control conditions were poorly correlated, suggesting that distinct genetic factors regulate training effects and normal immune responses. Subsequent quantitative trait loci analysis suggested that four loci containing 80 genes may be involved in regulating innate immune memory. Among them, Adgf-A, which encodes an extracellular adenosine deaminase-related growth factor, was shown to be associated with training effects. Our study findings help to elucidate the genetic architecture of innate immune memory in Drosophila and may provide insight for new therapeutic treatments aimed at boosting immunity.
Genomic Characterization of Lactiplantibacillus plantarum Strains Possessing Differential Antiviral Immunomodulatory Activities International-journal International-coauthorship Peer-reviewed

1　136-160　2022/07/06
Publisher:
DOI： 10.3390/bacteria1030012 　
Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina International-journal International-coauthorship Peer-reviewed

Leonardo Albarracin, Ramiro Ortiz Moyano, Juan Martin Vargas, Bruno G. N. Andrade, Juan Cortez Zamar, Stefania Dentice Maidana, Kohtaro Fukuyama, Shoichiro Kurata, María Ángela Jure, Haruki Kitazawa, Julio Villena

International Journal of Molecular Sciences　23　(13)　7361-7361　2022/07/01
Publisher: {MDPI} {AG}
DOI： 10.3390/ijms23137361 　

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IF = 6.208
cGMP signaling pathway that modulates NF-κB activation in innate immune responses

Hirotaka Kanoh, Shinzo Iwashita, Takayuki Kuraishi, Akira Goto, Naoyuki Fuse, Haruna Ueno, Mariko Nimura, Tomohito Oyama, Chang Tang, Ryo Watanabe, Aki Hori, Yoshiki Momiuchi, Hiroki Ishikawa, Hiroaki Suzuki, Kumiko Nabe, Takeshi Takagaki, Masataka Fukuzaki, Li-Li Tong, Sinya Yamada, Yoshiteru Oshima, Toshiro Aigaki, Julian A.T. Dow, Shireen-Anne Davies, Shoichiro Kurata

iScience　24　(12)　103473-103473　2021/12
Publisher: Elsevier BV
DOI： 10.1016/j.isci.2021.103473 　

ISSN： 2589-0042
The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae International-journal Peer-reviewed

9:1324　1-19　2021/06
Publisher:
DOI： 10.3390/microorganisms9061324 　
Ligilactobacillus salivarius Strains Isolated From the Porcine Gut Modulate Innate Immune Responses in Epithelial Cells and Improve Protection Against Intestinal Viral-Bacterial Superinfection. International-journal

Yuhki Indo, Shugo Kitahara, Mikado Tomokiyo, Shota Araki, Md Aminul Islam, Binghui Zhou, Leonardo Albarracin, Ayako Miyazaki, Wakako Ikeda-Ohtsubo, Tomonori Nochi, Takato Takenouchi, Hirohide Uenishi, Hisashi Aso, Hideki Takahashi, Shoichiro Kurata, Julio Villena, Haruki Kitazawa

Frontiers in immunology　12　652923-652923　2021

DOI： 10.3389/fimmu.2021.652923 　

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Previously, we constructed a library of Ligilactobacillus salivarius strains from the intestine of wakame-fed pigs and reported a strain-dependent capacity to modulate IFN-β expression in porcine intestinal epithelial (PIE) cells. In this work, we further characterized the immunomodulatory activities of L. salivarius strains from wakame-fed pigs by evaluating their ability to modulate TLR3- and TLR4-mediated innate immune responses in PIE cells. Two strains with a remarkable immunomodulatory potential were selected: L. salivarius FFIG35 and FFIG58. Both strains improved IFN-β, IFN-λ and antiviral factors expression in PIE cells after TLR3 activation, which correlated with an enhanced resistance to rotavirus infection. Moreover, a model of enterotoxigenic E. coli (ETEC)/rotavirus superinfection in PIE cells was developed. Cells were more susceptible to rotavirus infection when the challenge occurred in conjunction with ETEC compared to the virus alone. However, L. salivarius FFIG35 and FFIG58 maintained their ability to enhance IFN-β, IFN-λ and antiviral factors expression in PIE cells, and to reduce rotavirus replication in the context of superinfection. We also demonstrated that FFIG35 and FFIG58 strains regulated the immune response of PIE cells to rotavirus challenge or ETEC/rotavirus superinfection through the modulation of negative regulators of the TLR signaling pathway. In vivo studies performed in mice models confirmed the ability of L. salivarius FFIG58 to beneficially modulate the innate immune response and protect against ETEC infection. The results of this work contribute to the understanding of beneficial lactobacilli interactions with epithelial cells and allow us to hypothesize that the FFIG35 or FFIG58 strains could be used for the development of highly efficient functional feed to improve immune health status and reduce the severity of intestinal infections and superinfections in weaned piglets.
Homeostatic Regulation of ROS-Triggered Hippo-Yki Pathway via Autophagic Clearance of Ref(2)P/p62 in the Drosophila Intestine

Hiroki Nagai, Hiroshi Tatara, Kyoko Tanaka-Furuhashi, Shoichiro Kurata, Tamaki Yano

Developmental Cell　56　(1)　81-94.e10　2021/01
Publisher: Elsevier BV
DOI： 10.1016/j.devcel.2020.12.007 　

ISSN： 1534-5807
Selection of Immunobiotic Ligilactobacillus salivarius Strains from the Intestinal Tract of Wakame-Fed Pigs: Functional and Genomic Studies International-journal

Binghui Zhou, Leonardo Albarracin, Yuhki Indo, Lorena Arce, Yuki Masumizu, Mikado Tomokiyo, Md. Aminul Islam, Valeria Garcia-Castillo, Wakako Ikeda-Ohtsubo, Tomonori Nochi, Hidetoshi Morita, Hideki Takahashi, Shoichiro Kurata, Julio Villena, Haruki Kitazawa

Microorganisms　8　(11)　1659-1659　2020/10/26
Publisher: MDPI AG
DOI： 10.3390/microorganisms8111659 　

eISSN： 2076-2607

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In this article, Ligilactobacillus salivarius FFIG strains, isolated from the intestinal tract of wakame-fed pigs, are characterized according to their potential probiotic properties. Strains were evaluated by studying their interaction with porcine intestinal epithelial (PIE) cells in terms of their ability to regulate toll-like receptor (TLR)-3- or TLR4-mediated innate immune responses, as well as by assessing their adhesion capabilities to porcine epithelial cells and mucins. These functional studies were complemented with comparative genomic evaluations using the complete genome sequences of porcine L. salivarius strains selected from subgroups that demonstrated different “immune” and “adhesion” phenotypes. We found that their immunomodulatory and adhesion capabilities are a strain-dependent characteristic. Our analysis indicated that the differential immunomodulatory and adhesive activities of FFIG strains would be dependent on the combination of several surface structures acting simultaneously, which include peptidoglycan, exopolysaccharides, lipoteichoic acid, and adhesins. Of note, our results indicate that there is no correlation between the immunomodulatory capacity of the strains with their adhesion ability to mucins and epithelial cells. Therefore, in the selection of strains destined to colonize the intestinal mucosa and modulate the immunity of the host, both properties must be adequately evaluated. Interestingly, we showed that L. salivarius FFIG58 functionally modulated the innate immune responses triggered by TLR3 and TLR4 activation in PIE cells and efficiently adhered to these cells. Moreover, the FFIG58 strain was capable of reducing rotavirus replication in PIE cells. Therefore, L. salivarius FFIG58 is a good candidate for further in vivo studying the protective effect of lactobacilli against intestinal infections in the porcine host. We also reported and analyzed, for the first time, the complete genome of several L. salivarius strains that were isolated from the intestine of pigs after the selective pressure of feeding the animals with wakame. Further genomic analysis could be of value to reveal the metabolic characteristics and potential of the FFIG strains in general and of the FFIG58 strain, in particular, relating to wakame by-products assimilation.
The Role of Alveolar Macrophages in the Improved Protection against Respiratory Syncytial Virus and Pneumococcal Superinfection Induced by the Peptidoglycan of Lactobacillus rhamnosus CRL1505 International-journal

Patricia Clua, Mikado Tomokiyo, Fernanda Raya Tonetti, Md. Aminul Islam, Valeria García Castillo, Guillermo Marcial, Susana Salva, Susana Alvarez, Hideki Takahashi, Shoichiro Kurata, Haruki Kitazawa, Julio Villena

Cells　9　(7)　1653-1653　2020/07/09
Publisher: MDPI AG
DOI： 10.3390/cells9071653 　

eISSN： 2073-4409

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The nasal priming with nonviable Lactobacillus rhamnosus CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulates the respiratory innate immune response in infant mice, improving their resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, it was found that NV1505 or PG1505 significantly enhance the numbers of CD11c+SiglecF+ alveolar macrophages (AMs) producing interferon (IFN)-β. In this work, we aimed to further advance in the characterization of the beneficial effects of NV1505 and PG1505 in the context of a respiratory superinfection by evaluating whether their immunomodulatory properties are dependent on AM functions. Macrophage depletion experiments and a detailed study of their production of cytokines and antiviral factors clearly demonstrated the key role of this immune cell population in the improvement of both the reduction of pathogens loads and the protection against lung tissue damage induced by the immunobiotic CRL1505 strain. Studies at basal conditions during primary RSV or S. pneumoniae infections, as well as during secondary pneumococcal pneumonia, brought the following five notable findings regarding the immunomodulatory effects of NV1505 and PG1505: (a) AMs play a key role in the beneficial modulation of the respiratory innate immune response and protection against RSV infection, (b) AMs are necessary for improved protection against primary and secondary pneumococcal pneumonia, (c) the generation of activated/trained AMs would be essential for the enhanced protection against respiratory pathogens, (d) other immune and nonimmune cell populations in the respiratory tract may contribute to the protection against bacterial and viral infections, and (e) the immunomodulatory properties of NV1505 and PG1505 are strain-specific. These findings significantly improve our knowledge about the immunological mechanisms involved in the modulation of respiratory immunity induced by beneficial microbes.
Erratum: Evaluation of the immunomodulatory ability of lactic acid bacteria isolated from feedlot cattle against mastitis using a bovine mammary epithelial cells in vitro assay (Pathogens, (2020) 9, 5, 10.3390/pathogens9050410)

Kohtaro Fukuyama, Md. Aminul Islam, Michihiro Takagi, Wakako Ikeda-Ohtsubo, Shoichiro Kurata, Hisashi Aso, Maria Elena Fatima Nader-Macías, Graciela Vignolo, Julio Villena, Haruki Kitazawa

Pathogens　9　(7)　1-2　2020/07/01
Publisher: MDPI AG
DOI： 10.3390/pathogens9070574 　

ISSN： 2076-0817
Evaluation of the Immunomodulatory Ability of Lactic Acid Bacteria Isolated from Feedlot Cattle Against Mastitis Using a Bovine Mammary Epithelial Cells In Vitro Assay International-journal

Kohtaro Fukuyama, Md. Aminul Islam, Michihiro Takagi, Wakako Ikeda-Ohtsubo, Shoichiro Kurata, Hisashi Aso, Graciela Vignolo, Julio Villena, Haruki Kitazawa

Pathogens　9　(5)　410-410　2020/05/25
Publisher: MDPI AG
DOI： 10.3390/pathogens9050410 　

eISSN： 2076-0817

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Bovine mastitis, the inflammation of the mammary gland, affects the quality and quantity of milk yield. Mastitis control relies on single or multiple combinations of antibiotic therapy. Due to increasing antibiotic resistance in pathogens, the intramammary infusion of lactic acid bacteria (LAB) has been considered as a potential alternative to antibiotics for treating and preventing bovine mastitis through the improvement of the host immunity. Probiotic effects are a strain-dependent characteristic; therefore, candidate LAB strains have to be evaluated efficiently to find out the ones with the best potential. Here, we investigated LAB strains originally isolated from feedlot cattle’s environment regarding their ability in inducing the Toll-like receptor (TLR)-triggered inflammatory responses in bovine mammary epithelial (BME) cells in vitro. The BME cells were pre-stimulated with the LAB strains individually for 12, 24, and 48 h and then challenged with Escherichia coli-derived lipopolysaccharide (LPS) for 12 h. The mRNA expression of selected immune genes—interleukin 1 alpha (IL-1α), IL-1β, monocyte chemotactic protein 1 (MCP-1), IL-8, chemokine (C-X-C motif) ligand 2 (CXCL2), and CXCL3 were quantified by real-time quantitative PCR (RT-qPCR). Results indicated that pretreatment with some Lactobacillus strains were able to differentially regulate the LPS inflammatory response in BME cells; however, strain-dependent differences were found. The most remarkable effects were found for Lactobacillus acidophilus CRL2074, which reduced the expression of IL-1α, IL-1β, MCP-1, IL-8, and CXCL3, whereas Lactobacillus rhamnosus CRL2084 diminished IL-1β, MCP-1, and IL-8 expression. The pre-stimulation of BME cells with the CRL2074 strain resulted in the upregulated expression of three negative regulators of the TLRs, including the ubiquitin-editing enzyme A20 (also called tumor necrosis factor alpha-induced protein 3, TNFAIP3), single immunoglobin IL-1 single receptor (SIGIRR), and Toll interacting protein (Tollip) after the LPS challenge. The CRL2084 pre-stimulation upregulated only Tollip expression. Our results demonstrated that the L. acidophilus CRL2074 strain possess remarkable immunomodulatory abilities against LPS-induced inflammation in BME cells. This Lactobacillus strain could be used as candidate for in vivo testing due to its beneficial effects in bovine mastitis through intramammary infusion. Our findings also suggest that the BME cells immunoassay system could be of value for the in vitro evaluation of the immunomodulatory abilities of LAB against the inflammation resulting from the intramammary infection with mastitis-related pathogens.
The Ability of Respiratory Commensal Bacteria to Beneficially Modulate the Lung Innate Immune Response Is a Strain Dependent Characteristic

Ramiro Ortiz Moyano, Fernanda Raya Tonetti, Mikado Tomokiyo, Paulraj Kanmani, María Guadalupe Vizoso-Pinto, Hojun Kim, Sandra Quilodrán-Vega, Vyacheslav Melnikov, Susana Alvarez, Hideki Takahashi, Shoichiro Kurata, Haruki Kitazawa, Julio Villena

Microorganisms　8　(5)　727-727　2020/05/13
Publisher: MDPI AG
DOI： 10.3390/microorganisms8050727 　

eISSN： 2076-2607

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We investigated whether the ability of commensal respiratory bacteria to modulate the innate immune response against bacterial and viral pathogens was a shared or strain-specific characteristic. Bacterial strains belonging to the Corynebacterium pseudodiphtheriticum and Dolosigranulum pigrum species were compared by studying their influence in the Toll-like receptor (TLR)-2- and TLR3-triggered immune responses in the respiratory tract, as well as in the resistance to Respiratory Syncytial Virus (RSV) and Streptococcus pneumoniae infections. We demonstrated that nasally administered C. pseudodiphteriticum 090104 or D. pigrum 040417 were able to modulate respiratory immunity and increase the resistance against pathogens, while other strains of the same species did not influence the respiratory immune responses, demonstrating a clear strain-dependent immunomodulatory effect of respiratory commensal bacteria. We also reported here that bacterium-like particles (BLP) and cell walls derived from immunomodulatory respiratory commensal bacteria are an interesting alternative for the modulation of the respiratory immune system. Our study is a step forward in the positioning of certain strains of respiratory commensal bacteria as next-generation probiotics for the respiratory tract.
Immunoglobulin superfamily beat‐Ib mediates intestinal regeneration induced by reactive oxygen species in Drosophila

Hiroki Nagai, Shoichiro Kurata, Tamaki Yano

Genes to Cells　25　(5)　343-349　2020/05
Publisher: Wiley
DOI： 10.1111/gtc.12762 　

ISSN： 1356-9597

eISSN： 1365-2443
Cell fate plasticity and chromatin regulations；a view from Drosophila imaginal disc transdetermination Invited Peer-reviewed

Journal of Japanese Biochemical Society　92　(1)　124-129　2020
A Receptor Guanylate Cyclase, Gyc76C, Mediates Humoral, and Cellular Responses in Distinct Ways in Drosophila Immunity. International-journal Peer-reviewed

Shinzo Iwashita, Hiroaki Suzuki, Akira Goto, Tomohito Oyama, Hirotaka Kanoh, Takayuki Kuraishi, Naoyuki Fuse, Tamaki Yano, Yoshiteru Oshima, Julian A T Dow, Shireen-Anne Davies, Shoichiro Kurata

Frontiers in immunology　11　35-35　2020

DOI： 10.3389/fimmu.2020.00035 　

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Innate immunity is an evolutionarily conserved host defense system against infections. The fruit fly Drosophila relies solely on innate immunity for infection defense, and the conservation of innate immunity makes Drosophila an ideal model for understanding the principles of innate immunity, which comprises both humoral and cellular responses. The mechanisms underlying the coordination of humoral and cellular responses, however, has remained unclear. Previously, we identified Gyc76C, a receptor-type guanylate cyclase that produces cyclic guanosine monophosphate (cGMP), as an immune receptor in Drosophila. Gyc76C mediates the induction of antimicrobial peptides for humoral responses by a novel cGMP pathway including a membrane-localized cGMP-dependent protein kinase, DG2, through downstream components of the Toll receptor such as dMyD88. Here we show that Gyc76C is also required for the proliferation of blood cells (hemocytes) for cellular responses to bacterial infections. In contrast to Gyc76C-dependent antimicrobial peptide induction, Gyc76C-dependent hemocyte proliferation is meditated by a small GTPase, Ras85D, and not by DG2 or dMyD88, indicating that Gyc76C mediates the cellular and humoral immune responses in distinct ways.
HSP70/DNAJA3 chaperone/cochaperone regulates NF-κB activity in immune responses. Peer-reviewed

Kumada K, Fuse N, Tamura T, Okamori C, Kurata S

Biochemical and biophysical research communications　513　(4)　947-951　2019/06/11

DOI： 10.1016/j.bbrc.2019.04.077 　

ISSN： 0006-291X
Dual comprehensive approach to decipher the Drosophila Toll pathway, ex vivo RNAi screenings and immunoprecipitation-mass spectrometry. International-journal Peer-reviewed

Hirotaka Kanoh, Hiroyuki Kato, Yamato Suda, Aki Hori, Shoichiro Kurata, Takayuki Kuraishi

Biochemical and biophysical research communications　508　(1)　332-337　2019/01/01

DOI： 10.1016/j.bbrc.2018.11.007 　

ISSN： 0006-291X

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The Drosophila Toll pathway is involved in embryonic development, innate immunity, and cell-cell interactions. However, compared to the mammalian Toll-like receptor innate immune pathway, its intracellular signaling mechanisms are not fully understood. We have previously performed a series of ex vivo genome-wide RNAi screenings to identify genes required for the activation of the Toll pathway. In this study, we have conducted an additional genome-wide RNAi screening using the overexpression of Tube, an adapter molecule in the Toll pathway, and have performed a co-immunoprecipitation assay to identify components present in the dMyd88-Tube complex. Based on the results of these assays, we have performed a bioinformatic analysis, and describe candidate molecules and post-translational modifications that could be involved in Drosophila Toll signaling.
Nuclear Lamin is required for Winged Eye-mediated transdetermination of Drosophila imaginal disc. Peer-reviewed

Masuko K, Furuhashi H, Komaba K, Numao E, Nakajima R, Fuse N, Kurata S

Genes to cells : devoted to molecular & cellular mechanisms　23　(8)　724-731　2018/07

DOI： 10.1111/gtc.12608 　

ISSN： 1356-9597
winged eye Induces Transdetermination of Drosophila Imaginal Disc by Acting in Concert with a Histone Methyltransferase, Su(var)3-9 Peer-reviewed

Keita Masuko, Naoyuki Fuse, Kanae Komaba, Tomonori Katsuyama, Rumi Nakajima, Hirofumi Furuhashi, Shoichiro Kurata

Cell Reports　22　(1)　206-217　2018/01/02

DOI： 10.1016/j.celrep.2017.11.105 　

ISSN： 2211-1247
Unexpected role of the IMD pathway in Drosophila gut defense against Staphylococcus aureus Peer-reviewed

Aki Hori, Shoichiro Kurata, Takayuki Kuraishi

Biochemical and Biophysical Research Communications　495　(1)　395-400　2018/01/01

DOI： 10.1016/j.bbrc.2017.11.004 　

ISSN： 1090-2104 0006-291X
A novel mode of induction of the humoral innate immune response in Drosophila larvae Peer-reviewed

Hiroyuki Kenmoku, Aki Hori, Takayuki Kuraishi, Shoichiro Kurata

DISEASE MODELS & MECHANISMS　10　(3)　271-281　2017/03

DOI： 10.1242/dmm.027102 　

ISSN： 1754-8403

eISSN： 1754-8411
A subset of neurons controls the permeability of the peritrophic matrix and midgut structure in Drosophila adults Peer-reviewed

Hiroyuki Kenmoku, Hiroki Ishikawa, Manabu Ote, Takayuki Kuraishi, Shoichiro Kurata

JOURNAL OF EXPERIMENTAL BIOLOGY　219　(15)　2331-2339　2016/08

DOI： 10.1242/jeb.122960 　

ISSN： 0022-0949

eISSN： 1477-9145
Design and Synthesis of Structure-Simplified Derivatives of Gonytolide for the Promotion of Innate Immune Responses Peer-reviewed

Haruhisa Kikuchi, Tsuyoshi Hoshikawa, Shoichiro Kurata, Yasuhiro Katou, Yoshiteru Oshima

JOURNAL OF NATURAL PRODUCTS　79　(5)　1259-1266　2016/05

DOI： 10.1021/acs.jnatprod.5b00829 　

ISSN： 0163-3864

eISSN： 1520-6025
Organ identity specification factor WGE localizes to the histone locus body and regulates histone expression to ensure genomic stability in Drosophila Peer-reviewed

Nao Ozawa, Hirofumi Furuhashi, Keita Masuko, Eriko Numao, Takashi Makino, Tamaki Yano, Shoichiro Kurata

GENES TO CELLS　21　(5)　442-456　2016/05

DOI： 10.1111/gtc.12354 　

ISSN： 1356-9597

eISSN： 1365-2443
Organ identity specification factor WGE localizes to the histone locus body and regulates heterochromatin structure in Drosophila Peer-reviewed

Ozawa N, Furuhashi H, Masuko K, Numao E, Makino T, Yano T, Kurata S

Genes to Cells　2016/03

DOI： 10.1111/gtc.12354 　
The Drosophila Toll Pathway: A Model of Innate Immune Signalling Activated by Endogenous Ligands

Takayuki Kuraishi, Hirotaka Kanoh, Yoshiki Momiuchi, Hiroyuki Kenmoku, Shoichiro Kurata

Chronic Inflammation　119-129　2016
Publisher: Springer Japan
DOI： 10.1007/978-4-431-56068-5_10 　
From mouth to anus: Functional and structural relevance of enteric neurons in the Drosophila melanogaster gut Peer-reviewed

Takayuki Kuraishi, Hiroyuki Kenmoku, Shoichiro Kurata

INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY　67　21-26　2015/12

DOI： 10.1016/j.ibmb.2015.07.003 　

ISSN： 0965-1748

eISSN： 1879-0240
Ex vivo genome-wide RNAi screening of the Drosophila Toll signaling pathway elicited by a larva-derived tissue extract Peer-reviewed

Hirotaka Kanoh, Takayuki Kuraishi, Li-Li Tong, Ryo Watanabe, Shinji Nagata, Shoichiro Kurata

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　467　(2)　400-406　2015/11

DOI： 10.1016/j.bbrc.2015.09.138 　

ISSN： 0006-291X

eISSN： 1090-2104
Genome-wide RNAi screening implicates the E3 ubiquitin ligase Sherpa in mediating innate immune signaling by Toll in Drosophila adults Peer-reviewed

Hirotaka Kanoh, Li-Li Tong, Takayuki Kuraishi, Yamato Suda, Yoshiki Momiuchi, Fumi Shishido, Shoichiro Kurata

SCIENCE SIGNALING　8　(400)　ra107　2015/10

DOI： 10.1126/scisignal.2005971 　

ISSN： 1945-0877

eISSN： 1937-9145
The Role of the Phylogenetically Conserved Cochaperone Protein Droj2/DNAJA3 in NF-kappa B Signaling Peer-reviewed

Yoshiki Momiuchi, Kohei Kumada, Takayuki Kuraishi, Takeshi Takagaki, Toshiro Aigaki, Yoshiteru Oshima, Shoichiro Kurata

JOURNAL OF BIOLOGICAL CHEMISTRY　290　(39)　23816-23825　2015/09

DOI： 10.1074/jbc.M115.664193 　

ISSN： 0021-9258

eISSN： 1083-351X
ZFC3H1, a Zinc Finger Protein, Modulates IL-8 Transcription by Binding with Celastramycin A, a Potential Immune Suppressor (vol 9, e108957, 2014) Peer-reviewed

Takeshi Tomita, Katsuaki Ieguchi, Frederic Coin, Yasuhiro Kato, Haruhisa Kikuchi, Yoshiteru Oshima, Shoichiro Kurata, Yoshiro Maru

PLOS ONE　10　(9)　e0138262　2015/09

DOI： 10.1371/journal.pone.0138262 　

ISSN： 1932-6203
Isolation of a Cyclic Depsipetide, Aspergillicin F, and Synthesis of Aspergillicins with Innate Immune-Modulating Activity Peer-reviewed

Haruhisa Kikuchi, Tsuyoshi Hoshikawa, Shimpei Fujimura, Noriaki Sakata, Shoichiro Kurata, Yasuhiro Katou, Yoshiteru Oshima

JOURNAL OF NATURAL PRODUCTS　78　(8)　1949-1956　2015/08

DOI： 10.1021/acs.jnatprod.5b00286 　

ISSN： 0163-3864

eISSN： 1520-6025
神経系によるショウジョウバエ腸管の構造と機能の制御

見目裕之, 堀亜紀, 倉石貴透, 倉田祥一朗

蚕糸・昆虫バイオテック　84　(3)　3_205-3_212　2015
Publisher: 社団法人日本蚕糸学会
DOI： 10.11416/konchubiotec.84.3_205 　
ZFC3H1, a Zinc Finger Protein, Modulates IL-8 Transcription by Binding with Celastramycin A, a Potential Immune Suppressor Peer-reviewed

Takeshi Tomita, Katsuaki Ieguchi, Fredric Coin, Yasuhiro Kato, Haruhisa Kikuchi, Yoshiteru Oshima, Shoichiro Kurata, Yoshiro Maru

PLOS ONE　9　(9)　e108957　2014/09

DOI： 10.1371/journal.pone.0108957 　

ISSN： 1932-6203
Report on the 25th Annual Meeting of the Japanese Association for Developmental and Comparative Immunology (JADCI), August 26 (Monday) to 28 (Wednesday), 2013, the 50th Year Commemorative Building of Okayama University of Science, Okayama 700-0005, Japan (Local Organizer, Nobuhiko Asada) Peer-reviewed

Nobuhiko Asada, Ryosuke Iijima, Shoichiro Kurata

DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY　45　(2)　199-200　2014/08

DOI： 10.1016/j.dci.2014.02.011 　

ISSN： 0145-305X

eISSN： 1879-0089
Elimination of Intracellular Bacteria by Autophagy Peer-reviewed

Tamaki Yano, Shoichiro Kurata

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging　3　203-210　2014/01/31
Publisher: Elsevier Inc.
DOI： 10.1016/B978-0-12-405529-2.00014-7 　
Peptidoglycan recognition proteins in Drosophila immunity Peer-reviewed

Shoichiro Kurata

DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY　42　(1)　36-41　2014/01

DOI： 10.1016/j.dci.2013.06.006 　

ISSN： 0145-305X

eISSN： 1879-0089
Search of compounds acting on the innate immunity using Drosophila Peer-reviewed

Shoichiro Kurata

Seikagaku　86　(5)　583-587　2014
Publisher: Japanese Biochemical Society
ISSN： 2189-0544 0037-1017
The Organ Identity Specification Factor Winged Eye Participates in Epigenetic Regulation in Drosophila melanogaster Peer-reviewed

Keita Masuko, Eriko Numao, Hiroshi Kimura, Hirofumi Furuhashi, Shoichiro Kurata

GENES & GENETIC SYSTEMS　88　(6)　365-365　2013/12

ISSN： 1341-7568

eISSN： 1880-5779
Terresterol, a polyoxygenated lanostanoid, isolated from the oomycete Saprolegnia terrestris, and its innate immune-promoting activity Peer-reviewed

Haruhisa Kikuchi, Yuichi Sato, Shoichiro Kurata, Yasuhiro Katou, Yoshiteru Oshima

TETRAHEDRON　69　(17)　3536-3542　2013/04

DOI： 10.1016/j.tet.2013.02.088 　

ISSN： 0040-4020
Ectopic Antenna Induction by Overexpression of CG17836/Xrp1 Encoding an AT-Hook DNA Binding Motif Protein in Drosophila Peer-reviewed

Noriko Tsurui-Nishimura, Thanh Quang Nguyen, Tomonori Katsuyama, Tatsurou Minami, Hirofumi Furuhashi, Yoshiteru Oshima, Shoichiro Kurata

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY　77　(2)　339-344　2013/02

DOI： 10.1271/bbb.120756 　

ISSN： 0916-8451

eISSN： 1347-6947
Host-microbe interactions in the gut of Drosophila melanogaster Peer-reviewed

Takayuki Kuraishi, Aki Hori, Shoichiro Kurata

Frontiers in Physiology　4　375　2013

DOI： 10.3389/fphys.2013.00375 　

ISSN： 1664-042X
New dimeric and monomeric chromanones, gonytolides D-G, isolated from the fungus Gonytrichum sp. Peer-reviewed

Haruhisa Kikuchi, Masato Isobe, Shoichiro Kurata, Yasuhiro Katou, Yoshiteru Oshima

TETRAHEDRON　68　(31)　6218-6223　2012/08

DOI： 10.1016/j.tet.2012.05.064 　

ISSN： 0040-4020
ショウジョウバエ腸管での免疫応答と制御

倉石貴透, 倉田祥一朗

化学と生物　50　(6)　435-440　2012/06/01
Publisher: Japan Society for Bioscience, Biotechnology, and Agrochemistry
DOI： 10.1271/kagakutoseibutsu.50.435 　

ISSN： 0453-073X
A receptor guanylyl cyclase mediating Tollin-dependent/dMyD88-dependent humoral response and dMyD88-independent cellular response in Drosophila immunity

Kanoh, H., Suzuki, H., Iwashita, S., Goto, A., Kuraishi, T., Dow, J., Davies, S. -A., Kurata, S.

Febs Journal　279　150-150　2012
Drosophila growth-blocking peptide-like factor mediates acute immune reactions during infectious and non-infectious stress Peer-reviewed

Seiji Tsuzuki, Masanori Ochiai, Hitoshi Matsumoto, Shoichiro Kurata, Atsushi Ohnishi, Yoichi Hayakawa

SCIENTIFIC REPORTS　2　210　2012/01

DOI： 10.1038/srep00210 　

ISSN： 2045-2322
Coleopteran antimicrobial peptides: Prospects for clinical applications Peer-reviewed

Monde Ntwasa, Akira Goto, Shoichiro Kurata

International Journal of Microbiology　2012　101989　2012

DOI： 10.1155/2012/101989 　

ISSN： 1687-918X 1687-9198
A phytoceramide analog stimulates the production of chemokines through CREB activation in human endothelial cells Peer-reviewed

Mizuki Sekiya, Kazunori Ueda, Kaori Okazaki, Jun Terashima, Yasuhiro Katou, Haruhisa Kikuchi, Shoichiro Kurata, Yoshiteru Oshima

INTERNATIONAL IMMUNOPHARMACOLOGY　11　(10)　1497-1503　2011/10

DOI： 10.1016/j.intimp.2011.05.001 　

ISSN： 1567-5769
Structures of the Dimeric and Monomeric Chromanones, Gonytolides A-C, Isolated from the Fungus Gonytrichum sp and Their Promoting Activities of Innate Immune Responses Peer-reviewed

Haruhisa Kikuchi, Masato Isobe, Mizuki Sekiya, Yuko Abe, Tsuyoshi Hoshikawa, Kazunori Ueda, Shoichiro Kurata, Yasuhiro Katou, Yoshiteru Oshima

ORGANIC LETTERS　13　(17)　4624-4627　2011/09

DOI： 10.1021/ol2018449 　

ISSN： 1523-7060

eISSN： 1523-7052
Intracellular recognition of pathogens and autophagy as an innate immune host defence Peer-reviewed

Tamaki Yano, Shoichiro Kurata

JOURNAL OF BIOCHEMISTRY　150　(2)　143-149　2011/08

DOI： 10.1093/jb/mvr083 　

ISSN： 0021-924X
Synthesis and innate immunosuppressive effect of 1,2-cyclopentanediol derivatives Peer-reviewed

Haruhisa Kikuchi, Kaori Okazaki, Mizuki Sekiya, Yasuyuki Uryu, Kazunori Ueda, Yasuhiro Katou, Shoichiro Kurata, Yoshiteru Oshima

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY　46　(4)　1263-1273　2011/04

DOI： 10.1016/j.ejmech.2011.01.049 　

ISSN： 0223-5234
Exploitation of new biological resources, entomopathogenic fungi and oomycetes

Kikuchi Haruhisa, Sato Yuichi, Hoshi Tomoko, Kitayama Minoru, Sekiya Mizuki, Isobe Masato, Mihara Ken, Katou Yasuhiro, Kurata Shoichiro, Oshima Yoshiteru, Kubohara Yuzuru, Sato Hiroki, Shimazu Mitsuaki

Symposium on the Chemistry of Natural Products, symposium papers　(52)　703-708　2010/09/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.52.0_703 　

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Entomopathogenic fungi infect insects through the cuticle, grow as hyphal bodies or hyphae in the hemocoel, and cause host death by nutritional destruction of tissues, and producint toxic metabolites and pathogenic enzymes. To date, entomopathogenic fungi have not been extensively studied by natural product chemists. We focused on entomopathogenic fungi as new resources for biologically active compounds, and studied the diversity of their secondary metabolites. In this study, we show the isolation and structure elucidation of novel pyrone diterpene-type compounds, metarhizin A-H (1-8) from Metarhizium flavoviride, and their antiproliferative activities on human cancer cell lines. Additionally, we synthesized many metarhizin derivatives, evaluated their antiproliferative activities, and discuss the structural requirements for this activity. A novel pyrone diterpene-type compound, Nf-1 (9), was also isolated from Nectria flammea. Oomycetes from fungus-like mycelium and were calssified as fungi in the past. However, the cell walls of them are c omposed of cellulose rather than chitin, as in the fungi. In the present, the ultrastructure, biochemistry and molecular sequences of them indicate that the oomycetes belong to the Kingdom Chromista, not the Kingdom Fungi. We also focused on oomycetes as new resources for natural product chemistry. A new oxidized lanostane-type compound, St-1 (23), was isolated from the mycelium of oomycete Saprolegnia terrestris. The structure of 23 was determined by spectral means including EIMS, and ^1H and ^<13>C NMR.
Cooperative Regulation of the Induction of the Novel Antibacterial Listericin by Peptidoglycan Recognition Protein LE and the JAK-STAT Pathway Peer-reviewed

Akira Goto, Tamaki Yano, Jun Terashima, Shinzo Iwashita, Yoshiteru Oshima, Shoichiro Kurata

JOURNAL OF BIOLOGICAL CHEMISTRY　285　(21)　15731-15738　2010/05

DOI： 10.1074/jbc.M109.082115 　

ISSN： 0021-9258
Extracellular and intracellular pathogen recognition by Drosophila PGRP-LE and PGRP-LC Peer-reviewed

Shoichiro Kurata

INTERNATIONAL IMMUNOLOGY　22　(3)　143-148　2010/03

DOI： 10.1093/intimm/dxp128 　

ISSN： 0953-8178

eISSN： 1460-2377
FLY IMMUNITY: Recognition of Pathogens and Induction of Immune Responses Peer-reviewed

Shoichiro Kurata

INVERTEBRATE IMMUNITY　708　205-217　2010

DOI： 10.1007/978-1-4419-8059-5-11 　

ISSN： 0065-2598
Exploration of Innate Immune Regulators from Natural Resources

Kikuchi Haruhisa, Sekiya Mizuki, Isobe Masato, Kabeya Takahiro, Nakamura Tetsuya, Ueda Kazunori, Katou Yasuhiro, Kurata Shoichiro, Oshima Yoshiteru

Symposium on the Chemistry of Natural Products, symposium papers　(51)　545-550　2009/09/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.51.0_545 　

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Innate immunity is the first line of defense against infectious microorganisms, and the basic mechanisms of this process, including pathogen recognition and immune response activation, are evolutionarily conserved. In mammals, the innate immunity has an instructive role in the adaptive immune response specific to antigen by inducing co-stimulatory molecules and cytokines, indicating that a concerted and interactive innate and adaptive immune reaction is key for the regulated immune response. Therefore, from a pharmaceutical point of view, innate immunity is a good target for the development of immune regulators to suppress unwanted immune responses, such as septic shock, inflammatory diseases and autoimmunity, and to stimulate protective immune responses to some of the disease that largely elude the immune system, such as infectious diseases and cancer. To screen pharmaceuticals that target innate immunity, we established an ex vivo culture system based on the innate immune response of Drosophila, which is highly useful for idintifying immune regulators that act on human innate immunity. We used this system to search for natural substances that regulate innate immunity, and identified celastramycin A (1) and TP-554 (2) as a potent suppressor and an activator, respectively. The previously reported structure 3 for celastramycin A was corrected to 1 by synthesizing both compounds. In addition, we synthesized some derivatives of celastramycin A (1) to evaluate structure-activity relationship of these compounds.
Induction of autophagy via intracellular innate immune recognition in Drosophila Peer-reviewed

Shoichiro Kurata

AUTOPHAGY　5　(6)　910-910　2009/08

ISSN： 1554-8627
Epigenetic regulation of winged eye capable of inducing transformation in Drosophila Peer-reviewed

Rumi Nakajima, Tomonori Katsuyama, Jun Terashima, Yoshiteru Oshima, Shoichiro Kurata

MECHANISMS OF DEVELOPMENT　126　S117-S118　2009/08

DOI： 10.1016/j.mod.2009.06.222 　

ISSN： 0925-4773
Revised Structure and Synthesis of Celastramycin A, A Potent Innate Immune Suppressor Peer-reviewed

Haruhisa Kikuchi, Mizuki Sekiya, Yasuhiro Katou, Kazunori Ueda, Takahiro Kabeya, Shoichiro Kurata, Yoshiteru Oshima

ORGANIC LETTERS　11　(8)　1693-1695　2009/04

DOI： 10.1021/ol9002306 　

ISSN： 1523-7060
An unexpected twist for autophagy in Crohn's disease Invited Peer-reviewed

Tamaki Yano, Shoichiro Kurata

NATURE IMMUNOLOGY　10　(2)　134-136　2009/02

DOI： 10.1038/ni0209-134 　

ISSN： 1529-2908
An unexpected twist for autophagy in Crohn's disease Peer-reviewed

Tamaki Yano, Shoichiro Kurata

NATURE IMMUNOLOGY　10　(2)　134-136　2009/02

DOI： 10.1038/ni0209-134 　

ISSN： 1529-2908
New diterpene pyrone-type compounds, metarhizins A and B, isolated from entomopathogenic fungus, Metarhizium flavoviride and their inhibitory effects on cellular proliferation Peer-reviewed

Haruhisa Kikuchi, Tomoko Hoshi, Minoru Kitayama, Mizuki Sekiya, Yasuhiro Katou, Kazunori Ueda, Yuzuru Kubohara, Hiroki Sato, Mitsuaki Shimazu, Shoichiro Kurata, Yoshiteru Oshima

TETRAHEDRON　65　(2)　469-477　2009/01

DOI： 10.1016/j.tet.2008.11.014 　

ISSN： 0040-4020
昆虫の自然免疫機構を解き明かす Invited

倉田祥一朗

化学療法の領域　64　12-17　2009/01
Induction of autophagy via innate bacterial recognition Invited Peer-reviewed

Tamaki Yano, Shoichiro Kurata

AUTOPHAGY　4　(7)　958-960　2008/10

DOI： 10.4161/auto.6802 　

ISSN： 1554-8627
ハエから夢見る再生医療 Invited

倉田祥一朗

ファルマシア　44　1059-1062　2008/08
Autophagic control of listeria through intracellular innate immune recognition in drosophila Peer-reviewed

Tamaki Yano, Shizuka Mita, Hiroko Ohmori, Yoshiteru Oshima, Yukari Fujimoto, Ryu Ueda, Haruhiko Takada, William E. Goldman, Koichi Fukase, Neal Silverman, Tamotsu Yoshimori, Shoichiro Kurata

NATURE IMMUNOLOGY　9　(8)　908-916　2008/08

DOI： 10.1038/ni.1634 　

ISSN： 1529-2908
A cyclopentanediol analogue selectively suppresses the conserved innate immunity pathways, Drosophila IMD and TNF-alpha pathways Peer-reviewed

Mizuki Sekiya, Kazunori Ueda, Kaori Okazaki, Haruhisa Kikuchi, Shoichiro Kurata, Yoshiteru Oshima

BIOCHEMICAL PHARMACOLOGY　75　(11)　2165-2174　2008/06

DOI： 10.1016/j.bcp.2007.12.020 　

ISSN： 0006-2952
The YPWM motif links Antennapedia to the basal transcriptional machinery Peer-reviewed

Frederic Prince, Tomonori Katsuyama, Yoshiteru Oshima, Serge Plaza, Diana Resendez-Perez, Meera Berry, Shoichiro Kurata, Walter J. Gehring

DEVELOPMENT　135　(9)　1669-1679　2008/05

DOI： 10.1242/dev.018028 　

ISSN： 0950-1991
P-51 Exploration and Pharmaceutical Development of New Immune Regulators from Natural Resources

Kikuchi Haruhisa, Sekiya Mizuki, Okazaki Kaori, Ueda Kazunori, Kurata Shoichiro, Oshima Yoshiteru

Symposium on the Chemistry of Natural Products, symposium papers　(49)　389-394　2007/08/24
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.49.0_389 　

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Innate immunity is the first line of defense against infectious microorganisms. The basic mechanisms of pathogen recognition and response activation are evolutionarily conserved. In mammals, the innate immunity has an instructive role in the adaptive immune response specific to antigen by inducing co-stimulatory molecules and cytokines, indicating that a concerted and interactive innate and adaptive immune reaction is key for the regulated immune response. Therefore, from a pharmaceutical point of view, innate immunity is a good target for the development of immune regulators to suppress unwanted immune responses, such as septic shock, inflammatory diseases and autoimmunity, and to stimulate protective immune responses to some of the disease that largely elude the immune system, such as infectious diseases and cancer. For pharmaceutical screening, we established an in vitro culture based on the innate immune response of Drosophila, which is equivalent to that of mammals. The expression of a reporter gene, Dpt-lac Z, reflected the LPS-dependent activation of innate immunity. Search for natural substances regulating innate immunity by the systems led us the isolation of 17 compounds including a cyclopentanediol derivative, TP-1 (1), and a ceramide derivative, TP-76 (2), as innate immune suppressors. Furthermore, we synthesized some derivatives of TP-1 to evaluate structure-activity relationship of these compounds. Methylamide, phenylamide and methylsulfoneamide analogs exhibited innate immune suppressive activities 15 times more potent than that of TP-1 (1).
ショウジョウバエの菌体認識機構 Invited

倉田祥一朗

化学療法の領域　23　80-86　2007/02
自然免疫における病原体認識蛋白質の多機能性 Invited

倉田祥一朗

ブレインテクノニュース　119　26-29　2007/01
細胞内外での病原体認識と昆虫感染防御システム Invited

倉田祥一朗

バイオインダストリー　24　5-9　2007/01
Establishment of ex vivo systems to identify compounds acting on innate immune responses and to determine their target molecules using transgenic Drosophila Peer-reviewed

Mizuki Sekiya, Kazunori Ueda, Tomomitsu Fujita, Minoru Kitayama, Haruhisa Kikuchi, Yoshiteru Oshima, Shoichiro Kurata

LIFE SCIENCES　80　(2)　113-119　2006/12

DOI： 10.1016/j.lfs.2006.08.026 　

ISSN： 0024-3205
Recognition and elimination of diversified pathogens in insect defense systems Peer-reviewed

Shoichiro Kurata

MOLECULAR DIVERSITY　10　(4)　599-605　2006/11

DOI： 10.1007/s11030-006-9032-6 　

ISSN： 1381-1991
ハエの生活環と抗菌活性 Invited

倉田祥一朗

Pharma Medica　24　(2)　63-67　2006/10
昆虫の自然免疫メカニズムについて Invited

倉田祥一朗

Medical Entomology and Zoology　57　(2)　179-179　2006/10
Publisher: The Japan Society of Medical Entomology and Zoology
DOI： 10.7601/mez.57.179 　

ISSN： 0424-7086
The multiple functions of the PGRP family in Drosophila immunity Invited Peer-reviewed

Goto, A, Kurata, S

Invertebrate Survival Journal　3　103-110　2006/10
P-28 Exploration of new immune regulators from natural resources by Drosophila ex vivo systems and analysis of their regulation mechanism

Sekiya Mizuki, Ueda Kazunori, Kikuchi Haruhisa, Matsui Yuichi, Okazaki Kaori, Kurata Shoichiro, Oshima Yoshiteru

International Symposium on the Chemistry of Natural Products　2006　"P-28"　2006/07/23
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/intnaturalprod.2006.0__P-28_ 　
PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan Peer-reviewed

T Kaneko, T Yano, K Aggarwal, JH Lim, K Ueda, Y Oshima, C Peach, D Erturk-Hasdemir, WE Goldman, BH Oh, S Kurata, N Silverman

NATURE IMMUNOLOGY　7　(7)　715-723　2006/07

DOI： 10.1038/ni1356 　

ISSN： 1529-2908
Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins Peer-reviewed

JH Lim, MS Kim, HE Kim, T Yano, Y Oshima, K Aggarwal, WE Goldman, N Silverman, S Kurata, BH Oh

JOURNAL OF BIOLOGICAL CHEMISTRY　281　(12)　8286-8295　2006/03

DOI： 10.1074/jbc.M513030200 　

ISSN： 0021-9258
Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins Peer-reviewed

JH Lim, MS Kim, HE Kim, T Yano, Y Oshima, K Aggarwal, WE Goldman, N Silverman, S Kurata, BH Oh

JOURNAL OF BIOLOGICAL CHEMISTRY　281　(12)　8286-8295　2006/03

DOI： 10.1074/jbc.M513030200 　

ISSN： 0021-9258
Recognition of pathogens and activation of immune responses in Drosophila and horseshoe crab innate immunity Invited Peer-reviewed

Shoichiro Kurata, Shigeru Ariki, Shun-ichiro Kawabata

IMMUNOBIOLOGY　211　(4)　237-249　2006

DOI： 10.1016/j.imbio.2005.10.016 　

ISSN： 0171-2985
Intra- and extracellular recognition of pathogens and activation of innate immunity Peer-reviewed

Shoichiro Kurata

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN　126　(12)　1213-1218　2006

DOI： 10.1248/yakushi.126.1213 　

ISSN： 0031-6903
Involvement of winged eye encoding a chromatin-associated bromo-adjacent homology domain protein in disc specification Peer-reviewed

T Katsuyama, T Sugawara, M Tatsumi, Y Oshima, WJ Gehring, T Aigaki, S Kurata

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　102　(44)　15918-15923　2005/11

DOI： 10.1073/pnas.0507945102 　

ISSN： 0027-8424
自然免疫におけるPGRPファミリーの役割 Invited

倉田祥一朗

生化学　77　(9)　1184-1189　2005/10
Publisher:
ISSN： 0037-1017
Upregulation of PGRPs by chemically synthesized pathogen-associated molecular patterns via Toll-like receptors, NOD1 and NOD2 in oral epithelial cells Invited

Akiko Uehara, Yumiko Sugawara, Shoichiro Kurata, Yukari Fujimoto, Koichi Fukase, Shoichi Kusumoto, Takashi Sasano, Kenichiro Shibata, Shunji Sugawara, Haruhiko Takada

International Congress Series　1284　163-168　2005/09

DOI： 10.1016/j.ics.2005.06.032 　

ISSN： 0531-5131
A virus essential for insect host-parasite interactions encodes cystatins Peer-reviewed

E Espagne, Douris, V, G Lalmanach, B Provost, L Cattolico, J Lesobre, S Kurata, K Iatrou, JM Drezen, E Huguet

JOURNAL OF VIROLOGY　79　(15)　9765-9776　2005/08

DOI： 10.1128/JVI.79.15.9765-9776.2005 　

ISSN： 0022-538X
自然免疫におけるペプチドグリカン認識タンパク質ファミリーの役割 Invited

倉田祥一朗

日本細菌学雑誌　60　(2)　389-395　2005/06
Publisher: JAPANESE SOCIETY FOR BACTERIOLOGY
DOI： 10.3412/jsb.60.389 　

ISSN： 0021-4930
Chemically synthesized pathogen-associated molecular patterns increase the expression of peptidoglycan recognition proteins via Toll-like receptors, NOD1 and NOD2 in human oral epithelial cells Peer-reviewed

A Uehara, Y Sugawara, S Kurata, Y Fujimoto, K Fukase, S Kusumoto, Y Satta, T Sasano, S Sugawara, H Takada

CELLULAR MICROBIOLOGY　7　(5)　675-686　2005/05

DOI： 10.1111/j.1462-5822.2005.00500.x 　

ISSN： 1462-5814
[Role of peptidoglycan recognition protein family in innate immunity]. Peer-reviewed

Kurata S

Nihon saikingaku zasshi. Japanese journal of bacteriology　60　(2)　389-395　2005/05

ISSN： 0021-4930
Signaling pathways in innate immunity Invited

倉田祥一朗

臨床免疫学（上）－基礎研究の進歩と最新の臨床－　63　63-68　2005/04
[Signaling mechanisms in innate immunity]. Peer-reviewed

Kurata S

Nihon rinsho. Japanese journal of clinical medicine　63 Suppl 4　63-68　2005/04

ISSN： 0047-1852
Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity Peer-reviewed

A Takehana, T Yano, S Mita, A Kotani, Y Oshima, S Kurata

EMBO JOURNAL　23　(23)　4690-4700　2004/11

DOI： 10.1038/sj.emboj.7600466 　

ISSN： 0261-4189
92(P-18) Substances Regulating Innate Immunity from Microorganisms Including Entomopathogenic Fungi

Kikuchi Haruhisa, Ueda Kazunori, Sekiya Mizuki, Okazaki Kaori, Fujita Tomomitsu, Kitayama Minoru, Kurata Shoichiro, Oshima Yoshiteru, Hamaguchi Takuya, Kawashima Akira, Sato Hiroki, Shimazu Mitsuaki

Symposium on the Chemistry of Natural Products, symposium papers　(46)　527-532　2004/10/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.46.0_527 　

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Innate immunity is the first line of defense against infectious microorganisms. The basic mechanisms of pathogen recognition and response activation are evolutionarily conserved. In mammals, the innate immune response is required for the activation of acquired immunity. Therefore, innate immunity is a pharmaceutical target for the development of immune regulator. For pharmaceutical screening, we established an in vitro culture based on the innate immune response of Drosophila, which is equivalent to that of mammals. The expression of a reporter gene, Dpt-lac Z, reflected the LPS-dependent activation of innate immunity. In combination with the loss-of-function and gain-of-function mutation in the Drosophila immune response, the culture system has an advantage over conventional cell-line culture in identifying the target molecules that the chemicals affected. We screened the effect of ca. 400 extracts of microorganism including entomopathogenic fungi on innate immunity. TP-1 (1), ceramide 2 and cephalosporolide B (7) were isolated as specific inhibitor of the innate immune system. For further biological study, TP-1 (1) was synthesized from commercially available 3-cyclopentene-1-carboxylic acid.
Functional divergence between eyeless and twin of eyeless in Drosophila melanogaster Peer-reviewed

C Punzo, S Plaza, M Seimiya, P Schnupf, S Kurata, J Jaeger, WJ Gehring

DEVELOPMENT　131　(16)　3943-3953　2004/08

DOI： 10.1242/dev.01278 　

ISSN： 0950-1991
Functional divergence between eyeless and twin of eyeless in Drosophila melanogaster Peer-reviewed

C Punzo, S Plaza, M Seimiya, P Schnupf, S Kurata, J Jaeger, WJ Gehring

DEVELOPMENT　131　(16)　3943-3953　2004/08

DOI： 10.1242/dev.01278 　

ISSN： 0950-1991
Recognition of infectious non-self and activation of immune responses by Peptidoglycan Recognition Protein (PGRP)-family members in Drosophila Invited Peer-reviewed

倉田祥一朗

蛋白質核酸酵素　49　(8)　1174-1178　2004/06

ISSN： 0039-9450
An introduction: Innate immunity and non-self recognition Invited Peer-reviewed

Shoichiro Kurata

蛋白質核酸酵素　49　(8)　1153-1155　2004/06

ISSN： 0039-9450
Recognition of infectious non-self and activation of immune responses by Peptidoglycan Recognition Protein (PGRP)-family members in Drosophila Invited Peer-reviewed

Shoichiro Kurata

Dev. Comp. Immunol.　28　89-95　2004/04

DOI： 10.1016/S0145-305X(03)00121-6 　
Recognition of infectious non-self and activation of immune responses by peptidoglycan recognition protein (PGRP)-family members in Drosophila Peer-reviewed

S Kurata

DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY　28　(2)　89-95　2004/02

DOI： 10.1016/S0145-305X(03)00121-6 　

ISSN： 0145-305X
Developmental changes of poly(ADP-ribose) polymerase expression in Sarcophaga peregrina Peer-reviewed

Mitsuko Masutani, Miyoko Ikejima, Sofia Mariotto, Tadashige Nozaki, Shoichiro Kurata, Shunji Natori, Hiroyasu Esumi, Takashi Sugimura

Proceedings of the Japan Academy Series B: Physical and Biological Sciences　80　(7)　336-341　2004
Publisher: Japan Academy
DOI： 10.2183/pjab.80.336 　

ISSN： 0386-2208
A newly established in vitro culture using transgenic Drosophila reveals functional coupling between the phospholipase A(2)-generated fatty acid cascade and lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in insect immunity Peer-reviewed

M Yajima, M Takada, N Takahashi, H Kikuchi, S Natori, Y Oshima, S Kurata

BIOCHEMICAL JOURNAL　371　205-210　2003/04

DOI： 10.1042/BJ20021603 　

ISSN： 0264-6021
The mechanisms of non-self recognition in Drosophila immunity Invited

倉田祥一朗

分子細胞治療　2　598-604　2003/04
A newly established in vitro culture using transgenic Drosophila reveals functional coupling between the phospholipase A(2)-generated fatty acid cascade and lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in insect immunity Peer-reviewed

M Yajima, M Takada, N Takahashi, H Kikuchi, S Natori, Y Oshima, S Kurata

BIOCHEMICAL JOURNAL　371　(Pt 1)　205-210　2003/04

DOI： 10.1042/BJ20021603 　

ISSN： 0264-6021
Purification and characterization of poly(ADP-ribose) polymerase from Sarcophaga peregrina Peer-reviewed

Miyoko Ikejima, Tadashige Nozaki, Shoichiro Kurata, Shunji Natori, Hiroyasu Esumi, Takashi Sugimura, Mitsuko Masutani

Proceedings of the Japan Academy Series B: Physical and Biological Sciences　78　(9)　282-285　2002/11

DOI： 10.2183/pjab.78.282 　

ISSN： 0386-2208
insect immunity Invited

倉田祥一朗

医学の歩み　202　(11)　945-950　2002/11
pathogen recognition in innate immunity Invited

倉田祥一朗

細胞工学　21　(11)　1318-1319　2002/11
Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates imd/relish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae Peer-reviewed

A Takehana, T Katsuyama, T Yano, Y Oshima, H Takada, T Aigaki, S Kurata

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　99　(21)　13705-13710　2002/10

DOI： 10.1073/pnas.212301199 　

ISSN： 0027-8424
Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates imd/relish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae Peer-reviewed

A Takehana, T Katsuyama, T Yano, Y Oshima, H Takada, T Aigaki, S Kurata

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　99　(21)　13705-13710　2002/10

DOI： 10.1073/pnas.212301199 　

ISSN： 0027-8424
Determination of organ identity by Notch signaling Invited

倉田祥一朗

細胞工学　21　(5)　504-507　2002/05
Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies Peer-reviewed

Y Onuma, S Takahashi, M Asashima, S Kurata, WJ Gehring

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　99　(4)　2020-2025　2002/02

DOI： 10.1073/pnas.022626999 　

ISSN： 0027-8424
Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies Peer-reviewed

Y Onuma, S Takahashi, M Asashima, S Kurata, WJ Gehring

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　99　(4)　2020-2025　2002/02

DOI： 10.1073/pnas.022626999 　

ISSN： 0027-8424
The eyeless homeodomain is dispensable for eye development in Drosophila. Peer-reviewed

Punzo, C, Kurata, S, Gehring, W. J

Genes & Development　15　1716-1723　2001/06

DOI： 10.1101/gad.196401 　
Notchシグナリンブと器官アイデンティティーの決定 Invited

倉田祥一朗

実験医学　18　1347-1352　2000/04
ショウジョウバエの自然免疫を制御するシグナル伝達カスケード Invited

倉田祥一朗

生体の科学　51　(3)　202-207　2000/04

DOI： 10.11477/mf.2425902114 　
Notch signaling and the determination of appendage identity Peer-reviewed

Shoichiro Kurata, Masahiro J. Go, Spyros Artavanis-Tsakonas, Walter J. Gehring

Proceedings of the National Academy of Sciences of the United States of America　97　(5)　2117-2122　2000/02/29

DOI： 10.1073/pnas.040556497 　

ISSN： 0027-8424
Two subunits of the insect 26/29-kDa proteinase are probably derived from a common precursor protein Peer-reviewed

Yasuyuki Fujimoto, Ayako Kobayashi, Shoichiro Kurata, Shunji Natori

Journal of Biochemistry　125　(3)　566-573　1999
Publisher: Japanese Biochemical Society
DOI： 10.1093/oxfordjournals.jbchem.a022322 　

ISSN： 0021-924X
Selective inactivation of elongation factor-2 (EF-2) in free adipocytes obtained by treating Sarcophaga larval fat bodies with chymotrypsin Peer-reviewed

H Okuyama, S Kurata, K Homma, S Natori

INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY　28　(5-6)　301-307　1998/05

DOI： 10.1016/S0965-1748(98)00001-0 　

ISSN： 0965-1748
A novel lectin from Sarcophaga - Its purification, characterization, and cDNA cloning Peer-reviewed

Y Fujita, S Kurata, K Homma, S Natori

JOURNAL OF BIOLOGICAL CHEMISTRY　273　(16)　9667-9672　1998/04

DOI： 10.1074/jbc.273.16.9667 　

ISSN： 0021-9258
Purification and characterization of a 25 kDa cathepsin L-like protease from the hemocyte of coleopteran insect, Tenebrio molitor larvae. Peer-reviewed

Jang, K.S, Cho, M.Y, Choi, H.W, Lee, K.M, Kim, M.H, Lee, Y.U, Kurata, S, Natori, S, Lee, B.L

J Biochem. Mol. Biol.　31　364-369　1998/04
Purification and characterisation of cathepsin B mRNA 3'-untranslated-region-binding protein (CBBP), a protein that represses cathepsin B mRNA translation Peer-reviewed

T Yano, A Kobayashi, S Kurata, S Natori

EUROPEAN JOURNAL OF BIOCHEMISTRY　245　(2)　260-265　1997/04

DOI： 10.1111/j.1432-1033.1997.00260.x 　

ISSN： 0014-2956
Molecular cloning of cDNA for Sarcophaga prolyl endopeptidase and characterization of the recombinant enzyme produced by an E-coli expression system Peer-reviewed

S Ohtsuki, K Homma, S Kurata, S Natori

INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY　27　(4)　337-343　1997/04

DOI： 10.1016/S0965-1748(97)00004-0 　

ISSN： 0965-1748
Regeneration of Sarcophaga imaginal discs in vitro: Implication of 20-hydroxyecdysone Peer-reviewed

Takekazu Kunieda, Shoichiro Kurata, Shunji Natori

Developmental Biology　183　(1)　86-94　1997/03/01
Publisher: Academic Press Inc.
DOI： 10.1006/dbio.1996.8498 　

ISSN： 0012-1606
Nuclear localization and involvement in DNA synthesis of Sarcophaga prolyl endopeptidase Peer-reviewed

Sumio Ohtsuki, Ko-Ichi Homma, Shoichiro Kurata, Shunji Natori

Journal of Biochemistry　121　(6)　1176-1181　1997
Publisher: Oxford University Press
DOI： 10.1093/oxfordjournals.jbchem.a021712 　

ISSN： 0021-924X
Purification, characterization, and cDNA cloning of a galactose-specific C-type lectin from Drosophila melanogaster Peer-reviewed

Shafiqul Haq, Takeo Kubo, Shoichiro Kurata, Ayako Kobayashi, Shunji Natori

Journal of Biological Chemistry　271　(33)　20213-20218　1996

DOI： 10.1074/jbc.271.33.20213 　

ISSN： 0021-9258
Selective interaction of synthetic antimicrobial peptides derived from Sapecin B with lipid bilayers Peer-reviewed

Y Hirakura, J AlvarezBravo, S Kurata, S Natori, Y Kirino

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY　65　PC404-PC404　1996

ISSN： 0079-6107
Purification and characterization of N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine, a novel antibacterial substance of sarcophaga peregrina (flesh fly) Peer-reviewed

Jae Yoon Leem, Chiaki Nishimura, Shoichiro Kurata, Ichio Shimada, Ayako Kobayashi, Shunji Natori

Journal of Biological Chemistry　271　(23)　13573-13577　1996
Publisher: American Society for Biochemistry and Molecular Biology Inc.
DOI： 10.1074/jbc.271.23.13573 　

ISSN： 0021-9258
Molecular cloning of cDNA for sapecin B, an antibacterial protein of Sarcophaga, and its detection in larval brain Peer-reviewed

Se-Rok Lee, Shoichiro Kurata, Shunji Natori

FEBS Letters　368　(3)　485-487　1995/07/24

DOI： 10.1016/0014-5793(95)00717-N 　

ISSN： 0014-5793
Molecular Characterization of an Insect Transferrin and its Selective Incorporation into Eggs During Oogenesis Peer-reviewed

Takeshi Kurama, Shoichiro Kurata, Shunji Natori

European Journal of Biochemistry　228　(2)　229-235　1995

DOI： 10.1111/j.1432-1033.1995.tb20254.x 　

ISSN： 1432-1033 0014-2956
Purification of a 200 kDa protein-binding protein from the fat body of Sarcophaga peregrina larvae Peer-reviewed

Hideaki Kobayashi, Shoichiro Kurata, Shunji Natori

Insect Biochemistry and Molecular Biology　25　(3)　393-399　1995

DOI： 10.1016/0965-1748(94)00084-U 　

ISSN： 0965-1748
A Sapecin Homologue of Holotrichia Diomphalia: Purification, Sequencing and Determination of Disulfide Pairs Peer-reviewed

So Lee, Hyun Moon, Bok Lee, Shunichiro Kawabata, Shunji Natori, Shoichiro Kurata

Biological and Pharmaceutical Bulletin　18　(3)　457-459　1995

DOI： 10.1248/bpb.18.457 　

ISSN： 1347-5215 0918-6158
Mode of action of an antibacterial peptide, KLKLLLLLKLK-NH2 Peer-reviewed

Juan Alvarez-bravo, Shoichiro Kurata, Shunji Natori

Journal of Biochemistry　117　(6)　1312-1316　1995
Publisher: Oxford University Press
DOI： 10.1093/oxfordjournals.jbchem.a124860 　

ISSN： 0021-924X
Purification and cDNA Cloning of an Antifungal Protein from the Hemolymph of Holotrichia diomphalia Larvae Peer-reviewed

So young Lee, Hyun joo Moon, Bok luel Lee, Shoichiro Kurata, Shunji Natori

Biological and Pharmaceutical Bulletin　18　(8)　1049-1052　1995

DOI： 10.1248/bpb.18.1049 　

ISSN： 1347-5215 0918-6158
Regulation of the Expression of Cathepsin B in Sarcophaga Peregrina (Flesh Fly) at the Translational Level During Metamorphosis Peer-reviewed

Tamaki Yano, Noboru Takahashi, Shoichiro Kurata, Shunji Natori

European Journal of Biochemistry　234　(1)　39-43　1995

DOI： 10.1111/j.1432-1033.1995.039_c.x 　

ISSN： 1432-1033 0014-2956
STRUCTURE AND FUNCTION OF SAPECIN-B, A PEPTIDE BLOCKER OF POTASSIUM CHANNELS Peer-reviewed

JI KIM, H IWAI, S KURATA, M TAKAHASHI, K MASUDA, SHIMADA, I, S NATORI, Y ARATA, K SATO

PEPTIDE CHEMISTRY 1994　45-48　1995
Purification, Characterization, and cDNA Cloning of Procathepsin L from the Culture Medium of NIH-Sape-4, an Embryonic Cell Line of Sarcophaga peregrina (Flesh Fly), and Its Involvement in the Differentiation of Imaginal Discs Peer-reviewed

Ko-Ichi Homma, Shoichiro Kurata, Shunji Natori

Journal of Biological Chemistry　269　(21)　15258-15264　1994/05/27

ISSN： 0021-9258
SYNTHESIS AND CHARACTERIZATION OF SAPECIN AND SAPECIN-B Peer-reviewed

JI KIM, H IWAI, S KURATA, M TAKAHASHI, K MASUDA, SHIMADA, I, S NATORI, Y ARATA, K SATO

FEBS LETTERS　342　(2)　189-192　1994/04

DOI： 10.1016/0014-5793(94)80498-2 　

ISSN： 0014-5793
Inhibition of the Ca2v+-activated K+-channel by sapecin B, an insect antibacterial protein Peer-reviewed

Masafumi Shimoda, Hiroshi Takagi, Shoichiro Kurata, Tohru Yoshioka, Shunji Natori

FEBS Letters　339　(1-2)　59-62　1994/02/14

DOI： 10.1016/0014-5793(94)80384-6 　

ISSN： 0014-5793
D.P6 A hemocyte proteinase participating in decomposition of the larval fat body during metamorphosis of Sarcophaga peregrina (flesh fly)

Shoichiro Kurata, Shunji Natori

Developmental and Comparative Immunology　18　(1)　S85　1994
Publisher: Elsevier Ltd
DOI： 10.1016/0145-305X(94)90109-0 　

ISSN： 0145-305X
Purification and molecular cloning of cDNA for an inducible antibacterial protein of larvae of a coleopteran insect, Holotrichia diomphalia Peer-reviewed

So Young Lee, Hyun Joo Moon, Shoichiro Kurata, Takeshi Kurama, Shunji Natori, Bok Luel Lee

Journal of Biochemistry　115　(1)　82-86　1994
Publisher: Oxford University Press
DOI： 10.1093/oxfordjournals.jbchem.a124309 　

ISSN： 0021-924X
Selective cessation of protein synthesis in adipocytes produced by dissociating Sarcophaga larval fat body with chymotrypsin Peer-reviewed

Hajime Okuyama, Shoichiro Kurata, Shunji Natori

Insect Biochemistry and Molecular Biology　24　(5)　525-530　1994

DOI： 10.1016/0965-1748(94)90047-7 　

ISSN： 0965-1748
A prolyl endopeptidase of Sarcophaga peregrina (flesh fly): Its purification and suggestion for its participation in the differentiation of the imaginal discs Peer-reviewed

Sumio Ohtsuki, Ko-Ichi Homma, Shoichiro Kurata, Hiroto Komano, Shunji Natori

Journal of Biochemistry　115　(3)　449-453　1994
Publisher: Oxford University Press
DOI： 10.1093/oxfordjournals.jbchem.a124358 　

ISSN： 0021-924X
Novel synthetic antimicrobial peptides effective against methicillin-resistant Staphylococcus aureus Peer-reviewed

J. Alvarez-Bravo, S. Kurata, S. Natori

Biochemical Journal　302　(2)　535-538　1994
Publisher: Portland Press Ltd
DOI： 10.1042/bj3020535 　

ISSN： 0264-6021
Purification and molecular cloning of cDNA for an inducible antibacterial protein from larvae of the coleopteran, Tenebrio molitor Peer-reviewed

Hyun Joo Moon, So Young Lee, Shoichiro Kurata, Shunji Natori, Bok Luel Lee

Journal of Biochemistry　116　(1)　53-58　1994
Publisher: Oxford University Press
DOI： 10.1093/oxfordjournals.jbchem.a124502 　

ISSN： 0021-924X
Cloning and functional expression of poly(ADP‐ribose) polymerase cDNA from Sarcophaga peregrina Peer-reviewed

Mitsuko MASUTANI, Tadashige NOZAKI, Yoshiaki HITOMI, Miyoko IKEJIMA, Koichi NAGASAKI, Alessandra Carcereri DE PRATI, Shoichi KURATA, Shunji NATORI, Takashi SUGIMURA, Hiroyasu ESUMI

European Journal of Biochemistry　220　(2)　607-614　1994

DOI： 10.1111/j.1432-1033.1994.tb18662.x 　

ISSN： 1432-1033 0014-2956
Molecular cloning of cDNA for the 29 kDa proteinase participating in decomposition of the larval fat body during metamorphosis of Sarcophaga peregrina (flesh fly) Peer-reviewed

Noboru Takahashi, Shoichiro Kurata, Shunji Natori

FEBS Letters　334　(2)　153-157　1993/11/15

DOI： 10.1016/0014-5793(93)81702-2 　

ISSN： 0014-5793
昆虫の殺菌性蛋白 Invited

倉田祥一朗, 名取俊二

生体防御　10　133-139　1993/04
Purification and Heterogeneous Localization of Sarcophaga Lectin Receptor on the Surface of Imaginal Discs of Sarcophaga peregrina (Flesh Fly): (Sarcophaga peregrina/Sarcophaga Lectin/Receptor/Imaginal Discs/Monoclonal Antibody) Peer-reviewed

Yasuo Nagasawa, Shoichiro Kurata, Hiroto Komano, Shunji Natori

Development, Growth & Differentiation　35　(3)　331-340　1993

DOI： 10.1111/j.1440-169X.1993.00331.x 　

ISSN： 1440-169X 0012-1592
Purification, characterization, and cDNA cloning of an antifungal protein from the hemolymph of Sarcophaga peregrina (flesh fly) larvae Peer-reviewed

R. Iijima, S. Kurata, S. Natori

Journal of Biological Chemistry　268　(16)　12055-12061　1993

ISSN： 0021-9258
センチニクバエ蛹化時における幼虫脂肪体崩壊の機構 Invited

倉田祥一朗

蛋白質核酸酵素　37　(2)　101-108　1992/02
Publisher:
ISSN： 0039-9450
The 29-kDa hemocyte proteinase dissociates fat body at metamorphosis of Sarcophaga Peer-reviewed

Shoichiro Kurata, Hiromi Saito, Shunji Natori

Developmental Biology　153　(1)　115-121　1992

DOI： 10.1016/0012-1606(92)90096-Y 　

ISSN： 0012-1606
Purification of a 29‐kDa hemocyte proteinase of Sarcophaga peregrina Peer-reviewed

Shoichiro KURATA, Hiromi SAITO, Shunji NATORI

European Journal of Biochemistry　204　(2)　911-914　1992

DOI： 10.1111/j.1432-1033.1992.tb16711.x 　

ISSN： 1432-1033 0014-2956
Purification and characterization of a hemocyte proteinase of Sarcophaga, possibly participating in elimination of foreign substances Peer-reviewed

Hiromi SAITO, Shoichiro KURATA, Shunji NATORI

European Journal of Biochemistry　209　(3)　939-944　1992

DOI： 10.1111/j.1432-1033.1992.tb17366.x 　

ISSN： 1432-1033 0014-2956
Participation of a 200-kDa hemocyte membrane protein in the dissociation of the fat body at the metamorphosis of Sarcophaga Peer-reviewed

Shoichiro Kurata, Hideaki Kobayashi, Shunji Natori

Developmental Biology　146　(1)　179-185　1991

DOI： 10.1016/0012-1606(91)90458-F 　

ISSN： 0012-1606
PURIFICATION OF THE 200 KDA HEMOCYTE MEMBRANE-PROTEIN OF SARCOPHAGA-PEREGRINA AND ITS SPECIFIC INTERACTION WITH FAT-BODY Peer-reviewed

H KOBAYASHI, S KURATA, S NATORI

INSECT BIOCHEMISTRY　21　(5)　517-522　1991

DOI： 10.1016/0020-1790(91)90105-N 　

ISSN： 0020-1790
PARTICIPATION OF HEMOCYTE PROTEINASE IN DISSOCIATION OF THE FAT-BODY ON PUPATION OF SARCOPHAGA-PEREGRINA (FLESH FLY) Peer-reviewed

S KURATA, H SAITO, S NATORI

INSECT BIOCHEMISTRY　20　(5)　461-465　1990

DOI： 10.1016/0020-1790(90)90027-R 　

ISSN： 0020-1790
個体発生と生体防術の接点−センチニクバエの蛹の中で起こる自己認識の変換 Invited

倉田祥一朗, 名取俊二

現代化学　220　(7)　56-60　1989/07
DISSOCIATION OF SARCOPHAGA-PEREGRINA (FLESH FLY) FAT-BODY BY PUPAL HEMOCYTES INVITRO Peer-reviewed

S KURATA, H KOMANO, S NATORI

JOURNAL OF INSECT PHYSIOLOGY　35　(7)　559-565　1989

ISSN： 0022-1910
A glycoprotein of oviductal origin alters biochemical properties of the zona pellucida of hamster egg Peer-reviewed

Taneaki Oikawa, Yutaka Sendai, Sho‐Ichiro Kurata, Ryuzo Yanagimachi

Gamete Research　19　(2)　113-122　1988

DOI： 10.1002/mrd.1120190202 　

ISSN： 1554-3919 0148-7280
Inhibition of in vitro fertilization by a monoclonal antibody reacting with the zona pellucida of the oviductal egg but not with that of the ovarian egg of the golden hamster Peer-reviewed

Yasuko Sakai, Yoshihiko Araki, Takao Yamashita, Shoichiro Kurata, Taneaki Oikawa, Masahiko Hiroi, Fujiro Sendo

Journal of Reproductive Immunology　14　(2)　177-189　1988

DOI： 10.1016/0165-0378(88)90068-X 　

ISSN： 0165-0378
A MONOCLONAL-ANTIBODY REACTING WITH THE ZONA-PELLUCIDA OF THE OVIDUCTAL EGG BUT NOT WITH THAT OF THE OVARIAN EGG OF THE GOLDEN-HAMSTER Peer-reviewed

Y ARAKI, S KURATA, T OIKAWA, T YAMASHITA, M HIROI, M NAIKI, F SENDO

JOURNAL OF REPRODUCTIVE IMMUNOLOGY　11　(3)　193-208　1987/07

ISSN： 0165-0378

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Misc. 13

Regulation of gut starvation response through Drosophila NP3253 neurons

NGUYEN Quang-Dat, 藤井希帆, 石橋謙太朗, 布施直之, 大坪和香子, 北澤春樹, 谷本拓, 倉田祥一朗

日本分子生物学会年会プログラム・要旨集(Web)　46th　2023
Regulation of starvation response through neural control in Drosophila

藤井希帆, NGUYEN Quang-Dat, 石橋謙太朗, 布施直之, 谷本拓, 北澤春樹, 大坪和香子, 倉田祥一朗

日本分子生物学会年会プログラム・要旨集(Web)　46th　2023
Role of autophagy in Drosophila innate immunity

H. Nagai, T. Yano, S. Kurata

ISJ-INVERTEBRATE SURVIVAL JOURNAL　12　155-157　2015

ISSN： 1824-307X
新規抗菌ペプチドDrosophila Listericinの同定

後藤彰, 矢野環, 寺島潤, 倉田祥一朗

生化学　82　(7)　667　2010/07/25

ISSN： 0037-1017
複眼を翅に改変する遺伝子winged eyeによるエピジェネティック制御

中島瑠美, 勝山朋紀, 寺島潤, 倉田祥一朗

生化学　3P-0922　2007

ISSN： 0037-1017
Context-dependent involvement of winged eye encoding a chromatin-associated bromo-adjacent homology domain protein in Drosophila disc specification

S. Kurata, T. Katsuyama, T. Sugawara, M. Tatsumi, Y. Oshima, W. J. Gehring, T. Aigaki

MECHANISMS OF DEVELOPMENT　122　S51-S51　2005/09

ISSN： 0925-4773
Functional divergence between eyeless and twin of eyeless in Drosophila melanogaster (vol 131, pg 3943, 2004

C Punzo, S Plaza, M Seimiya, P Schnupf, S Kurata, J Jaeger, WJ Gehring

DEVELOPMENT　131　(18)　4635-4635　2004/09

ISSN： 0950-1991
The common mechanisms of determination of organ identity in Drosophila development

KURATA Shoichiro, GEHRING Walter J.

21　219-219　1998/12/01
体表傷害によりセンチニクバエ3齢幼虫体液細胞膜に発現する20kDaレクチンの解析

藤田義文, 倉田祥一朗, 本間光一, 名取俊二

日本分子生物学会年会プログラム・講演要旨集　19　389-389　1996/08/01
センチニクバエ成虫原基in vitro再生系における細胞増殖の検出

國枝武和, 倉田祥一朗, 小林綾子, 名取俊二

日本分子生物学会年会プログラム・講演要旨集　19　836-836　1996/08/01
Purification, characterization and bioactivation of new antibacterial substance from Boettcherisca peregrina.

林載允, 西村千秋, 嶋田一夫, 倉田祥一朗, 名取俊二, 深沢秀輔, 上原至雅

日本薬学会年会要旨集　116th　(Pt 3)　89　1996/03

ISSN： 0918-9823
Selective Interaction of Synthetic Antimicrobial Peptides Derived from Sapecin B with Lipid Bilayers.

Hirakura Yutaka, Alvarez-Bravo Juan, Kurata Sho-ichiro, Natori Shunji, Kirino Yutaka

J Biochem (Tokyo)　120　(6)　1130-1140　1996
Publisher: The Japanese Biochemical Society
ISSN： 0021-924X

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By measuring carboxyfluorescein leakage from liposomes and the increase in membrane current through planar lipid bilayer membranes, we examined the capacities of a series of low-molecular-weight cationic amphiphilic peptides derived from the α-helix domain of sapecin B for membrane-perturbation and ion-channel formation. Some of these peptides strongly interact with membranes containing acidic phospholipids and phosphatidylethanolamine, with a very negative potential, which are characteristic of the Escherichia coli membrane, in parallel with their antimicrobial activity. In contrast, they do not interact with membranes which predominantly contain choline phospholipids and cholesterol in their outer leaflets, with a slightly negative potential, all of which are characteristic of eukaryotic membranes, thereby providing a molecular basis for their selective toxicity. Membranes doped with these peptides are as permeable to inorganic phosphates as to chloride ions and are far more permeable to cations. The loss of inorganic phosphates may damage bacterial cells due to rapid depletion of cytoplasmic ATP. Examination of the structure-activity relationships of a series of derived peptides in their interaction with a model of the E. coli membrane confirmed the necessity of cationic amphiphilicity for the peptides to attack the bacterial membrane and to exhibit antimicrobial activity.
BIOCHEMICAL-ANALYSIS OF 2ZP-0 .3.

S KURATA, Y ARAKI, T OIKAWA

ZOOLOGICAL SCIENCE　3　(6)　1040-1040　1986/12

ISSN： 0289-0003

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Books and Other Publications 2

The origin of life science researches

Shoichiro Kurata

青山社　2003/04
細胞社会とその形成

名取俊二, 倉田祥一朗, 齊藤浩美

東京大学出版会　1989/04

Research Projects 41

Determination of organ identity Competitive

1990/04 - Present
Innate immunity Competitive

1990/04 - Present
自然免疫受容体TollとGyc76Cのリガンドアイソフォームの発現による免疫調節

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(B)

Institution: 東北大学

2022/04/01 - 2025/03/31
Homeostasis through regulation of gut microbiota by the nervous system

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2021/07/09 - 2023/03/31
Regulation of humoral and cellular immune responses by innate immune receptor Gyc76C in Drosophila

Kurata Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2019/04/01 - 2022/03/31

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Innate immunity is involved in chronic inflammatory diseases, cancer metastasis, and lifestyle diseases by recognition of self-ligands. Therefore, understanding of regulation mechanisms of innate immune system is indispensable for understanding of these diseases and drug discovery. We have identified novel cGMP signaling pathway that modulates NF-κB pathway in innate immunity. In this study, we have identified a novel receptor, Gyc76C, which regulates innate immunity. In this study, we have elucidated one aspect of the molecular mechanism by which Gyc76C regulates humoral and cellular immunity.
Neurons regulating immune system

Kurata Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2018/06/29 - 2020/03/31

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To elucidate the mechanism of immune regulation by the nervous system, we analyzed how NP3253 neurons, which regulate resistance to bacterial infection, regulate the immune system. To do so, we focused on the hedgehog (Hh) signal. The results showed that inhibition of Hh signaling in the NP3253 neurons reduced infection resistance, and conversely, activation of Hh signaling increased infection resistance. This suggests the involvement of Hh signaling in NP3253 neurons in host defense. In addition, we identified the 1141 gene as a gene whose expression fluctuated in a neural activity-dependent manner in the gut.
Studies of modulation mechanisms of NF-kB signaling by novel cGMP pathway

Kurata Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2016/04/01 - 2019/03/31

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Innate immunity is involved in chronic inflammatory diseases, cancer metastasis, and lifestyle diseases by recognition of self-ligands. Therefore, understanding of regulation mechanisms of innate immune system is indispensable for understanding of these diseases and drug discovery. We have identified novel cGMP signaling pathway that modulates NF-κB pathway in innate immunity. In this study, we investigated modulation mechanisms of NF-κB signaling by novel cGMP pathway.
RNA virus regulation based on symbiotic bacteria

Kurata Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2015/04/01 - 2017/03/31

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Recently, the viral diseases mediated by arthropods such as insects become severe problems due to globalization and climate changing. A big clue has been given to this problem from studies of symbiotic bacteria, which is that symbiotic bacteria, Wolbachia, inhibits the replication of RNA viruses in the host insect and induces host resistance against RNA viral infections. In this research, we developed a screening system necessary for the development of antiviral drugs based on the mechanism of virus resistance mediated by symbiotic bacteria.
細胞内共生細菌による宿主へのウイルス耐性付与機構の解明

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業新学術領域研究(研究領域提案型)

Category: 新学術領域研究(研究領域提案型)

Institution: 東北大学

2014/04/01 - 2016/03/31

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細胞内共生細菌は、自立増殖が出来ないために、宿主に利益を与え共生関係を維持する。2008年に、細胞内共生細菌であるボルバキアが、感染したショウジョウバエに、プラス鎖一本鎖RNAウイルスに対する抵抗性を付与することが報告された。ボルバキアは、垂直伝搬し自立増殖できない。したがって、この現象は、共生細菌が宿主を改変し、ウイルス感染を利用して共生細菌を保菌する個体群を維持し、共生細菌の伝搬を図る戦略と捉えることが出来る。しかしながら、この現象の分子機構は全く明らかにされていない。そこで、本研究では、共生細菌による宿主ウイルス耐性付与に関わる因子をゲノムワイドに探索した。そのために、研究代表者が確立した共生細菌によるウイルス増殖抑制を簡単に検出できるレポーターシステムを用いて、機能欠失型の遺伝学的スクリーニングと、機能獲得型の遺伝学的スクリーニングを行った。これまでに、機能欠失型の遺伝学的スクリーニングとして、標的遺伝子の発現を抑制できるRNAi系統ライブラリーの2480系統、遺伝子変異体ライブラリーの803系統を解析した。機能獲得型の遺伝学的スクリーニングとして、標的遺伝子を強制発現できる904系統の解析を行った。そして、二次スクリーニングを行い、共生細菌によるRNAウイルス抑制をキャンセルする系統として、RNAi系統ライブラリーから6系統、遺伝子変異体ライブラリーから5系統、強制発現ライブラリーから6系統を同定した。RNAi系統ライブラリーから同定した因子について、さらに解析を進めた結果、この因子は宿主内での共生細菌の増殖、あるいは共生過程に必要な因子であることが示唆された。
Function of simjang that enhances transdetermination of Drosophila imaginal discs

KURATA Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2013/04/01 - 2015/03/31

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The function of gene, simjang, that enhances transdetermination of Drosophila imaginal discs was analyzed in this study. Simjang enhanced the eye to wing transdetermination through Mi-2/NuRD complex. Furthermore, Simjang was suggested to enhance the transdetermination by re-programing of developmental program.
Analysis of novel cGMP pathway regulating innate immune responses

KURATA Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2012/04/01 - 2015/03/31

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A receptor-type guanylate cyclase, Gyc76C, is a novel receptor regulating innate immune responses. Gyc76C regulates the activation of humoral responses in cGMP-dependent manner, and the activation of cellular responses in cGMP-independent manner. This study identified several Gyc76C down-stream factors involving the Gyc76C-mediated activation of humoral responses, and the Gyc76C-mediated activation of cellular responses.
Homeostatic inflammation: Molecular basis and dysregulation

MIYAKE Kensuke, KAISHO Tsuneyasu, MUTA Tatsushi, KURATA Shoichiro, KURANAGA Erina, OGAWA Yoshihiro, MARU Yoshiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Institution: The University of Tokyo

2009/07/23 - 2014/03/31
HOMEOSTATIC INFLAMMATION IN DROSOPHILA

KURATA SHOICHIRO

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Institution: Tohoku University

2009/07/23 - 2014/03/31

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In this study, we investigated the molecular mechanisms of homeostatic inflammation focusing on three items (1) new receptor, Gyc76C, and its endogenous ligand, (2) pathogen sensor, PGRP-LE,-dependent induction of homeostatic inflammation, and (3) PGRP-LE-dependent autophagy induction, using Drosophila as a model system.
Functional analysis of epigenetic regulation in Drosophilaintestinal homeostasis

FURUHASHI Hirofumi, KURATA Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku University

2011 - 2012

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To identify novel, evolutionally conserved epigenetic mechanisms that regulate gut immunity or homeostasis, we explored chromatin modifiers involved in intestinal pathology using the Drosophila model system. We found that forced removal of histone H3 lysine36 methylation (H3K36me) in intestinal stem cell (ISC)/enteroblast (EB) increases the resistance to Pseudomonas aeruginosa infection. However, further analyses indicated that the forced H3K36me demethylation in ISC/EB causes over-activation of oxidative stress response genes and shortens lifespan. These results suggest that H3K36me might contribute to appropriate regulation of stress responses and/or the maintenance of homeostasis in Drosophila intestine.
Study of induction mechanisms of autophagy in innate immunity

KURATA Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2009 - 2011

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PGRP-LE, a pathogen sensor in Drosophila, induces autophagy after recognition of bacteria such as Listeria in the cytoplasm. A Drosophila homologue of p62 (SQSTM1)encoding by Ref(2)P was identified as a down-stream regulator showing direct binding to PGRP-LE, that is crucial for PGRP-LE-dependent induction of autophagy and host survival after Listerial infection. Moreover, a functional domain of PGRP-LE required for autophagy induction was identified.
Basic study on mechanisms of metacyclogenesis-related vector-parasite relationships

INOUE Noboru, KAWAZU Shin-ichiro, GOTO Yasuyuki, SUGIMOTO Chihiro, WATANABE Jyunichi, KURATA Shouichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Obihiro University of Agriculture and Veterinary Medicine

2009 - 2011

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The world's first whole life-cycle stage proteome and EST data bases were established. These databases could potentially promote basic studies on control measures of human and animal African trypanosomoses. In addition, identification, cloning and characterization of congolense epimastigote specific protein (CESP) provided a novel knowledge which enhances further studies on trypanosome control strategies in its vector insect, tsetse.
ペプチドグリカン認識蛋白質(PGRP)-LEによる細胞内寄生細菌の認識と排除機構

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2009 - 2009

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ショウジョウバエが有する病原体センサーであるPGRP-LEが、リステリア菌の細胞内感染を認知し、細胞内分解系であるオートファジーを誘導する機構を分子レベルで明らかにするために、今年度は、オートファジーの誘導に必要なPGRP-LE内の機能ドメインの同定を試みた。そのために、様々な領域を欠失した変異体型PGRP-LEをショウジョウバエS2細胞に発現した際に、変異体型PGRP-LEが、リステリア菌の細胞内感染を認知し、オートファジーを誘導するのかどうか調べた。その際、野生型のリステリア菌と共に、細胞質中に侵入できないリステリア変異株(ファゴソーム膜を傷害するリステリオリシン0を有していないために細胞質に侵入できない)を用いた場合と比較した。また、昨年度までの解析により、PGRP-LEは、オートファジーの誘導とは独立して抗菌ペプチド誘導のimd経路を活性化することが明らかとなっているので(Nature Immunol. 2008)、同様の解析をimd経路の活性化を指標に行い、オートファジーの誘導に特異的に必要とされるドメインの同定を試みた。その結果、N末端側に両者の免疫応答に必要な領域と、それぞれの免疫応答に必要な領域があることが示唆された。
病原体センサーによるオートファジー誘導機構の解明

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2009 - 2009

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オートファジーは、飢餓時などの際に、恒常性維持のために誘導される細胞内分解系であるが、近年、自己由来成分凝集体や、細胞内寄生細菌などの排除に重要な役割を担うことが明らかにされ、注目されている。ペプチドグリカン認識蛋白質(PGRP)-LEは、研究代表者が同定したショウジョウバエの自然免疫系で機能する病原体センサーであり、これまでにオートファジーを誘導することが示されている唯一の病原体センサーである。本研究では、細胞内分解系であるオートファジーが、病原体センサーにより、特異的に誘導される分子機構を明らかにするために、PGRP-LEに結合し、オートファジー誘導に関わるアダプター因子を同定することを試みた。これまでに、PGRP-LEの発現していないショウジョウバエマクロファージ様細胞S2細胞に、PGRP-LEを発現させると、PGRP-LE依存にオートファジーが誘導され、細胞内寄生細菌であるリステリア菌が排除されることが示されている。そこで、PGRP-LEに結合し、オートファジーを誘導する際に機能するアダプター分子を同定するために、タグ付きのPGRP-LEをS2細胞で発現し、PGRP-LEに結合する因子を、タグに対する抗体、あるいはPGRP-LEに対するモノクローナル抗体で共免疫沈降を行った。現在、オートファジーを誘導するために必要なドメインを持たないPGRP-LE変異体を同様に発現させ、共免疫沈降のコントロールとして用いることで、PGRP-LEによるオートファジー誘導に関わる特異的なアダプター分子を同定している。
細胞内細菌感染に対抗するオートファジー誘導機構

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業新学術領域研究(研究領域提案型)

Category: 新学術領域研究(研究領域提案型)

Institution: 東北大学

2009 - 2009
クロマチン結合タンパク質Winged eyeによるdecoding制御

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2008 - 2009

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本研究の目的は、研究代表者が新たに同定した、ショウジョウバエの複眼を翅に改変できるクロマチン結合タンパク質Winged eye(WGE)に着目し、WGEによるdecoding制御を解析し、「発生プログラム」として捉えられている「特定の遺伝情報の読み出し方」を決定する機構を理解することにある。WGEは、一端決定された発生プログラムを、別のプログラムに書き換えることができる。したがって、WGEによるdecoding制御を明らかにすることにより、遺伝情報の読み出し方1を上位で制御する機構が理解できる。wgeは、ホメオティック遺伝子であるAbd-Bのポリコーム遺伝子群(PcG)応答エレメント(PRE)に対してPcGと拮抗する作用を示すトリソラックス遺伝子群(trxG)様(活性化状態の維持)に働くことが示されている。そこで、本年度は、wgeがその過剰発現により複眼を翅に改変する際に誘導されるvestigial(vg)のPREに、Abd-BのPREと同様に、trxG様の作用を示すのか調べた。その結果、wgeは、Abd-BのPREは異なり、vgのPREに対しては、trxG様の作用と相反するPcG様(抑制状態の維持)の作用を示すことが明らかとなった。このことは、wgeが、状況に応じてPcG様と、trxG様の相反する二つの作用を示すことを示唆している。
ペプチドグリカン認識蛋白質(PGRP)-LEによる細胞内寄生細菌の認識と排除機構

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2007 - 2008

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本研究では、(1)リステリア菌を認識し、排除する過程に、PGRP-LEが重要な役割を果たしていることを示すと共に、(2)PGRP-LEにより細胞内で認識されたリステリア菌が、どのような分子機構により排除されるのかを明らかにすることを目的としている。昨年度は、(1)リステリア菌に対する感染抵抗性の発現におけるPGRP-LEの関与について解析し、リステリア菌を認識し、排除する過程に、PGRP-LEが重要な役割を果たしていることを明らかにした。今年度は、(2)PGRP-LEにより細胞内で認識されたリステリア菌が、どのような分子機構により排除されるのかを明らかにするために、オートファジーに着目し解析した。オートファジーは、LC3蛋白質にGFPをつないだキメラ蛋白質(GFP-LC3)の挙動を追うことで可視化できることが知られている。まず、野生型のショウジョウバエ成虫から回収した血液細胞では、リステリアを感染させるとGFP-LC3のドットが観察され、オートファジーが誘導されることを確認した。そこで、PGRP-LE変異体から回収した血液細胞に、リステリア菌を感染させたところ、GFP-LC3のドットが観察されずに、オートファジーが誘導されないことがわかった。次に、リステリア菌を感染させたS2細胞では、PGRP-LE依存にリステリア菌の排除が誘導されるが、このPGRP-LEに依存したリステリア菌の排除は、オートファジー誘導に必要なAtg5のノックダウンにより抑制され、オートファジーによりリステリア菌の排除が起きることが分かった。さらに、Atg5をノックダウンしたショウジョウバエに、リステリア菌を感染させると、PGRP-LEの変異体と同様に、その感染抵抗性が低下することを分かった。これらの結果は、PGRP-LEはオートファジーを誘導してリステリア菌を排除することを示している。
ショウジョウバエゲノム機能解析により得られた器官改変を誘導する遺伝子群の解析

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2006 - 2007

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本研穿の目的は、「ショウジョウバエのゲノム機能解析により得られた器官改変を誘導する遺伝子群について、その機能を解析することにより、ある特定の細胞集団で特定の発生プログラムが決定される機構を理解し、またその決定が転換するプロセスから発生プログラムの決定が細胞集団毎に維持される機構を理解する」ことにある。解析する遺伝子群は、複眼を翅、肢、あるいは触角に改変する遺伝子として、ゲノム機能を利用した網羅的探索により同定した遺伝子群である。平成19年度は、ATフックを有するタンパク質をコードし、複眼を触角に改変する遺伝子(ATフック遺伝子)を中心に解析を進めた。まず、ATフック遺伝子から発現する二つの転写産物を別々に複眼原基で過剰発現させ、複眼が触角に改変するのかどうか調べたところ、二つの転写産物の機能に違いがないことがわかった。次に、ATフック遺伝子を複眼原基で過剰発現させ、複眼を触角に改変させた際に、複眼原基におけるwinglessとDistallessの発現を調べたところ、異所的な発現が認められた。そこで、このwinglessとDistallesの発現を調べたところ、異所的な発現が認められた。そこで、このwinglessとDistallessの発現が、ATフック遺伝子により細胞自立的にもたらされるのか、それとも細胞非自立的、すなわち周りの細胞との関係においてもたらされるのかどうか、モザイク状にATフック遺伝子を複眼原基で過剰発現させ調べたところ、ATフック遺伝子を複眼原基で過剰発現させると、複眼が触角に転換するが、それと同時に、複眼原基において、細胞死が誘導されることが明らかとなった。そこで、この細胞死と、複眼から触角への転換が関係あるのかどうか、ATフック遺伝子を複眼原基で過剰発現させる際に、P35蛋白質を発現させ、細胞死を抑制した際の、複眼から触角への転換を調べた。その結果、ATフック遺伝子を発現させると誘導される細胞死と、複眼から触角への転換が関係ないことがわかった。
クロマチン結合タンパク質Winged eyeによるdecoding制御

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2006 - 2007

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本研究の目的は、「ショウジョウバエの複眼を翅に改変できるクロマチン結合タンパク質Winged eye(WGE)によるエピジェネティックな制御を解析し、特定の遺伝情報の読み出し方を上位で制御する機構を理解する」ことにある。これにより、同じゲノム情報から個別の特異性が発現する機構と、均一な細胞集団の一部で、その特異性が決定される機構についての理解が進むものと期待できる。Wgeは、複眼を、前後軸・背腹軸を有するほぼ完全な構造を有する翅へと改変する遺伝子として、ゲノム機能を利用した網羅的探索により同定した遺伝子である。これまでに、クロマチン上のWGEは、ポリコーム遺伝子群(PcG)のPSC蛋白質のクロマチン上の局在部位のほぼ全てを含有することが明らかとなっている。そこで、PcGが作用するシスエレメントであるポリコーム応答領域(PRE)を用いたエピジェネティックな遺伝子発現制御を調べる系(Fab7)を用いて、WGEがどのようなエピジェネティック制御を行うのか調べた。その結果、クロマチン上でWGEとPSCが共局在することに対応して、wgeは、ホメオティック遺伝子であるAbd-BのPREに対してPcGと拮抗する作用を示すトリソラックス遺伝子群(trxG)様(活性化状態の維持)の作用を示すことが明らかとなった。さらに、酵母two-hybrid系でWGEと相互作用する、機能未知の新しいタンパク質、WGE interacting protein(WIP)が、WGEと同様にクロマチンの特異的な部位に結合することを見いだした。
自然免疫による異物認識の分子基盤の研究成果とりまとめ

川畑俊一郎, 藤田禎三, 倉田祥一郎, 落合正則, 芦田正明

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 九州大学

2001 - 2006

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本特定領域研究で対象とする非自己認識蛋白質や受容体、さらに生体防御レクチンは、すべて微生物表層成分を直接認識する真のパターン認識分子であり、それらの構造と機能解析を進めることにより、パターン認識という魅惑的な概念に潜む本質の解明が可能と考えている。これまで、具体的には、配列決定された蛋白質全体あるいは、機能ドメインを用いてX線結晶解析とNMRにより立体構造を決定し、パターン認識を支える分子基盤を明らかにしてきた。また、生体防御レクチンや関連蛋白質のノックアウトマウスの解析を行って、補体系におけるレクチン経路の役割を解明した。一方では、ショウジョウバエで確立したゲノムワイド同定系を用いて、これまで未知であったパターン認識受容体としてペプチドグリカン認識タンパク質(PGRP)-LEを同定した。そして、PGRP-LEが感染細菌の有するペプチドグリカンの構造上の違いを識別して、その感染に適した免疫応答を誘導することを示すと共に、PGRP-LEが抗菌ペプチド産生経路(imd経路)を活性化するだけでなく、異物の隔離と創傷治癒に関わるフェノール酸化酵素系(proPO系)をも活性化することを明らかにしてきた。 18年度は、計画研究代表者、共同研究者、海外研究協力者、評価委員が一同に会する機会をもうけるために、平成18年8月10日、11日の両日にかけて、福岡リーセントホテルにおいて「成果とりまとめ公開シンポジウム」を開催するとともに、計画班会議を行って、研究成果のとりまとめを行った。さらに、未発表データについても今年度中にも原著論文を投稿できるように討論した。
Signaling cascade and network regulating innate immunity

KURATA Shoichiro, TAKAHATA Naoyuki, OCHIAI Masanori

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Priority Areas

Category: Grant-in-Aid for Scientific Research on Priority Areas

Institution: TOHOKU UNIVERCTIY

2001 - 2005

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Innate immunity is an evolutionarily conserved self-defense mechanism against microbial infections. Therefore, analysis of innate immune reactions using model organisms such as Drosophila will provide insight into the prevention of human infectious diseases. In Drosophila, the induction of antimicrobial peptides is a major immune response regulated by two distinct signaling pathways called the IMD pathway and the Toll pathway, which are similar to the tumor necrosis factor-a signaling and Toll-like receptor/interleukin-1 signaling pathways, respectively, in mammals. In contrast to mammalian Toll-like receptor, Drosophila Toll does not act as a receptor for pathogens. As a receptor for bacterial pathogens, we identified a peptidoglycan recognition protein (PGRP)-family member, PGRP-LE, which recognizes the peptidoglycan of Gram-negative bacteria (DAP-type) and activates the IMD pathway (PNAS, 2002). In addition to PGRP-LE, some PGRP-family members were found to act as invading bacterial recognition receptors guiding humoral and cellular immune reactions in the hemolymph and on the cell surface of immune-responsive cells in Drosophila. Upstream of some serine proteases, PGRP-LE is also required for activation of the prophenoloxidase (proPO) cascade, which is another major immune response in insects (EMBO J, 2004). In addition to the extracellular function in the hemolymph, PGRP-LE has an intracellular function of recognizing the DAP-type peptidoglycan in the cytoplasm (Nature Immunology, 2006). This is the first identified intracellular receptor for bacterial components in insects.
The role of Notch signaling in the transdetermination

KURATA Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2002 - 2003

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One of the fundamental questions in the developmental biology is how organ identity is determined. We have established a system, using transgenic Drosophila, which allows eye to wing, leg and antenna transformation by the activation of the Notch signaling. To determine the role of the Notch signaling in the transdetermination, we performed the GAL4-mediated gain-of-function mutant screen in the combination with the activation of the Notch signaling, using the GS strains in which a target sequence for GALA called UAS is inserted at random. Up to now about 10,000 strains were screened, and three strains were found to induce the eye to wing transformation. And the eye to antenna and the eye to leg transformation were induced in 23 strains and 11 strains, respectively. A novel gene encoding a Bromo-adjacent homology (BAH) domain protein was identified as a corresponding gene of a strain which induce the eye to wing transformation. The over-expression of the BAH domain protein was found to induce ectopic activation of the wing-specific enhancer of vestigial (vg) gene which regulates wing development, suggesting that the BAH domain protein regulates wing development up-stream of vg. Corresponding to this result, the BAH domain protein induced ectopic wings having antero-posterior and dorso-ventral axis which are not formed in the vg-induced ectopic wings. To confirm that the Notch signaling has similar function in the vertebrate development, we found that the Notch signaling regulates the expression of Pax6 gene in Xenopus eye development as well as Drosophila.
新しい機能獲得変異体スクリーニングによる自然免疫の分子機構の解明

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 東北大学

2002 - 2003

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本研究で推進した新しい機能獲得型変異体スクリーニングでは、ショウジョウバエに酵母の転写因子GAL4のターゲット配列UASをゲノムにランダムに導入し、その下流に位置する遺伝子を強制発現させる。そして、この人為的な遺伝子発現により自然免疫が活性化したかどうかを、同時に導入しているレポーター遺伝子の発現とフェノール酸化酵素系の活性化(メラニン化)でモニターするものである。このレポーター遺伝子は、自然免疫の活性化により発現が誘導される抗菌ペプチドのプロモーターを有しており、抗菌ペプチド産生誘導を可視化できる。これまでに,目標としていた4千系統の解析を行い,抗菌ペプチドの全身性の発現誘導を引き起こす系統を1系統、マルピーギ管(排出系上皮細胞)での局所的な抗菌ペプチドの発現誘導を引き起こす系統を1系統、さらに、フェノール酸化酵素系を活性化する系統を1系統同定した。全身性の抗菌ペプチドを誘導する系統では、構造上膜受容体をコードする遺伝子が同定きれ、全身性の抗菌ペプチド産生誘導を制御するimd経路で、これまで想定されていながら未同定であった膜上受容体をコードする遺伝子である可能性が指摘された。上皮細胞での局所的な抗菌ペプチドの発現誘導は、自然免疫の原型と考えられている。今回同定できたマルピーギ管特異的な系統は、これまで未解明のまま残されていた自然免疫の原型の分子機構解明に手がかりを与えると期待できる。
Identificaion of compounds acting innate immunity using a newly established in vitro screen

KURATA Shoichiro, KUBODERA Noboru

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2001 - 2003

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Innate immunity is the first line of defense against infectious microorganisms, and the basic mechanisms of pathogen recognition and activation of the response are evolutionary conserved. In Mammals, the innate immune response is required in combination with antigen-specific recognition for the activation of the adaptive immunity. Therefore, innate immunity is one of the pharmaceutical targets for the development of immune regulators. In this study, for the purpose of pharmaceutical screening, we established an in vitro culture based on innate immune response of Drosophila. The in vitro system is capable of measuring the lipopolysacharide (LPS)-dependent activation of the imd pathway that shows similarity to tumor necrosis factor (TNF) signaling pathway in mammals. From the screening with about 1,000 samples, we found that a cyclopentanediol derivative inhibits the LPS-dependent activation of the imd pathway. The cyclopentanediol derivative found to inhibit intracellular signaling cascade of the imd pathway from an adaptor protein called imd to Relish transcriptional factor. Because the intracellular signaling cascade of the imd pathway shows similarity to tumor necrosis factor (TNF) signaling pathway in mammals, we investigated whether the cyclopentanediol derivative inhibits human TNF signaling pathway, one of the innate immune response in human. We found that the cyclopentanediol derivative inhibit TNF-dependent induction of chemokines in human umbilical vein endothelial cells (HUVEC). These results suggest that the newly established system is useful for pharmaceutical screening in identification of compounds which act on innate immunity.
ショウジョウバエの器官アイデンティティーを決定するプログラムの網羅的解析

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究(C)

Category: 特定領域研究(C)

Institution: 東北大学

2001 - 2001

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本研究では、代表者が確立した器官改変系を用いて、器官特異性が決定されるまでに必要な遺伝子発現のカスケードと、それらの遺伝子間のクロストークを明らかにすることを目的としている。そのために、酵母の転写因子GAL4のターゲット配列UASをランダムに導入したショウジョウバエ系統(遺伝子サーチシステム)を用いて、複眼原基で活性化型Notchレセプターと同時に発現させたときに、複眼から翅、触角あるいは肢へと器官変換を誘導できる、UASの下流に存在する遺伝子を同定することにした。昨年度の結果より、器官改変が誘導される系統は全て、Notchシグナリングの活性化を伴わない場合、複眼の形成不全を引き起こすことが明らかとなった。そこで本研究では、Notchシグナリングの活性化を敢えて行わないで予備スクリーニングを行い、スクリーニングの効率化を図った。現在までに3645系統の解析を終え、複眼の形成不全を引き起こした系統について、Notchシグナリングの活性化を伴った場合に、器官改変を誘導するかどうか調べた。その結果、複眼が翅へと変換する系統を2系統、肢へと変換する系統を10系統、触角に変わる系統を22系統同定した。複眼が翅に変換する系統で解析を行い、Notchシグナリングが、異なるステップで、異なる遺伝子と共に働き、異なる遺伝子の発現を誘導することで、器官の改変を誘導することを明らかにした。このことは、器官形成のリプログラムのためには、多段階でNotchシグナリングが必要とされることを示唆している
Construction of New Biological Screening System Using Insects and Search for Biologically Active Substances from Natural Sources

OSHIMA Yoshiteru, KIKUCHI Haruhisa, KURATA Shoichiro, TAKAYA Yoshiaki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2000 - 2001

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(1) The immune response in Drosophila and other insects has recently received much interest as a model for innate immune reactions in general because it could lead to the understanding of the immune system of mammalians and the discovery of novel drugs. Thus, we constructed the novel screening system using transgenic Drosophila which is useful to search the compounds affecting the innate immunity. (2) We investigated the constituents of cellular slime molds to clarify the diversity of their secondary metabolites and to explore biologically active substances that could be useful for development of novel drugs. From their multicellular fruit bodies, we isolated novel α-pyronoids, aromatics, and amino sugar analogues showing a variety of biological activities.
Development of Novel Antimalarial Drugs Based on Plant Alkaloids

OSHIMA Yoshiteru, TAKAYA Yoshiaki, HATAKEYAMA Susumu, WATAYA Yusuke, KIKUCHI Haruhisa, KURATA Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2000 - 2001

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Although febrifugine and isofebrifugine, alkaloids isolated from Dichroa febrifuga roots, show powerful antimalarial activities against Plasmodium falciparum, their strong side effects such as emetic effect precluded their clinical use in malaria. However, their antimalarial potency makes them attractive substances as leads for developing new types of chemotherapeutic antimalarial drugs. We have thus evaluated the in vitro antimalarial activity of analogues of febrifugine and isofebrifugine. The activities of analogues derived from Df-1 and Df-2, condensation products of febrifugine and isofebrifugine with acetone, respectively, were also obtained. The oxidation and reduction derivatives of febrifugine were found to exhibit potential antimalarial activities with high selectivities against P. falciparum in vitro. Additionally, the Dess-Martin oxidation product of Df-1 was found to be strongly active with high selectivity against P. falciparum. A structure-activity relationship study demonstrates the essential role played by the 4-quinazolinone ring in the appearance of activity, and that the presence of a 1"-amino group and C-2', C-3" 0-functionalities are crucial in the activity of febrifugine.
自然免疫系を制御する脂質メディエーター

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業奨励研究(A)

Category: 奨励研究(A)

Institution: 東北大学

2000 - 2001

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これまで研究申請者は、獲得免疫系を持たないために自然免疫系だけを選択的に解析できる昆虫を用いて、昆虫が病原体の感染に応じて少なくとも8種類の脂肪酸を生合成することを明らかにした。これらは、一連のシグナル伝達カスケードの中間体であると考えららたが、このカスケードは、植物の防御反応カスケードと哺乳動物のアラキドン酸カスケードと共通項を示していた。そこで本研究では、このシグナル伝達カスケードが、自然免疫系のメディエーターとして働いているかどうか、遺伝子導入ショウジョウバエを用いて明らかにすることを目的とした。昨年度、レポーター遺伝子導入ショウジョウバエを用いて、ホスホリパーゼA2(PLA2)の阻害剤が、エンドトキシンで誘導された自然免疫の活性化を抑制することを明らかにした。さらに、アラキドン酸とγ-リノレン酸だけが特異的にこの抑制をキャンセルし、このほかの脂肪酸にはその活性がないことを明らかにした。そこで本年度は、内在性の免疫応答遺伝子の発現について解析した。その結果、PLA2の阻害剤が、自然免疫の活性化を抑制すること、さらに、アラキドン酸とγ-リノレン酸だけが特異的にこの抑制をキャンセルすることが確認できた。この結果は、病原体の感染に応じて誘導されたPLA2により、リン脂質より脂肪酸が遊離し、アラキドン酸とγ-リノレン酸が中間体となる活性化型脂質メディエーターに変換され、この脂質メディエーターが、自然免疫系を制御していることを示唆している。
Notchシグナリングを中心とした器官アイデンティティーの決定機構の解析

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究(A)

Category: 特定領域研究(A)

Institution: 東北大学

2000 - 2000

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これまでに,ショウジョウバエの主要な成虫器官である複眼,翅,触角そして肢の形成時には,Notchシグナリングが状況に応じて,これらの器官のアイデンティティー決定に重要な遺伝子の発現を誘導して、それぞれの器官形成を誘導するという基本的な共通機構が存在することを見いだした。本研究では、この系を用いて、Notchシグナリングと共に働き、器官の改変を誘導できる遺伝子を網羅的に同定することで、器官決定に必要な遺伝子発現のプログラムを明らかにすることを目的とした。Notchシグナリングと共に働き、器官の改変を誘導する遺伝子を同定するために、酵母の転写因子GAL4のターゲット配列UASをランダムにゲノムに挿入した系統を用いたgain-of-functionのミューントスクリーニングを行った。これまでに、およそ300系統の解析を終えているが、まず最初の驚きは、ほとんど全ての系統において、複眼の形態異常が観察されたことである。UAS下流の遺伝子を単独で発現させ、Notchシグナリングを同時に活性化しない場合は、表現型は現れず、この系におけるNotchシグナリング活性化の重要性が浮き彫りになった。Notchシグナリングは、その細胞で発現している遺伝子の発現状況に、細胞が応答できるように反応性を付加していることが考えられる。これは、これまでに提唱されていないNotchシグナリングの新しい機能として注目に値する。このスクリーニングの結果、複眼から翅への改変を誘導する系統GS1068を同定した。この系統では、UASの制御下に3種の遺伝子の発現が誘導されることが明らかとなった。
ショウジョウバエの器官アイデンティティーを決定するプログラムの網羅的解析

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究(C)

Category: 特定領域研究(C)

Institution: 東北大学

2000 - 2000

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器官のアイデンティティーがどのようにして決定されるのかという問題は、発生プログラムの基本をなす重要な問題である。これまで、ショウジョウバエの主要な成虫器官である、複眼、触角、翅、肢の全てにおいて、これらの形成をより上位で支配している遺伝子の発現を、Notchシグナリングを中心とした機構が共通に制御していることを明らかにした。そして、この共通機構からどの器官の誘導がなされるのかは、この機構と共に働く遺伝子の発現状況により決定されることを明らかにした。本研究では、ショウジョウバエを用いて、この共通機構から器官特異性が決定されるまでに必要な遺伝子発現のカスケードと、それらの遺伝子間のクロストークを明らかにすることを目的とした。そのために、酵母の転写因子GAL4のターゲット配列UASをランダムに導入したショウジョウバエ系統(遺伝子サーチシステム)を用いて、複眼原基でGAL4を発現させ、活性化型Notchレセプターと同時に発現させたときに、複眼から翅、触角あるいは肢へと器官変換を誘導できる、UASの下流に存在する遺伝子を同定することにした。現在までおよそ350系統のスクリーニングを終了しているが、すでに複眼が翅に変換する系統(GS1068)と複眼が触角に変換する系統(GS1129)を見出している。それぞれの系統においてゲノム上でのUAS挿入位置はすでに明らかとなっており、現在それらの遺伝子の同定を進めている。これまでに、GS1068はNotchシグナルと共に働きAntennapedia(Antp)の異所的な発現を誘導し、そのAntpが再びNotchシグナルと共に働き、翅の形成を支配するvestigialの発現を誘導し、複眼から翅への転換を誘導することを明らかにした。
昆虫複眼のマスターコントロール遺伝子eyelessによる器官特異性の決定機構

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究(A)

Category: 特定領域研究(A)

Institution: 東北大学

1999 - 1999

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これまでに昆虫の主な成虫器官である複眼,触覚,翅,肢を用いて,器官の特徴を決める多種の遺伝子の発現を,より上位で制御するそれぞれのマスターコントロール遺伝子の発現が,Notchシグナリングを中心とした共通の機構で制御されていることを明らかにしている. 本研究では,この共通機構からどのようにして器官の特異性が確立するのか明らかにするために,複眼を決定するeyeless(ey)遺伝子に着目し,(1)異所的発現系を用いて,複眼と触角をそれぞれ決定するey遺伝子と,Dll遺伝子・Exd遺伝子同士による相互の発現抑制が,複眼と触角の特異性を決めることを明らかにした.そしてこの特異性発現へ向けて、背側と腹側からのシグナル(dppとDorsal)が最初の違いを生むと予想していたが、活性化型dppレセプターを用いた実験から,背側と腹側からのシグナルだけでは、その特異性発現に不十分であることを示唆した.(2)ey蛋白には,二つのDNA結合部位,ペアードドメイン(PRD)とホメオドメイン(HD)が存在するが,ミュータントey蛋白の異所的発現系を用いて、それらには機能的な違いがあり,PRDが複眼への特異性発現を誘導し,HDが他の器官への特異性発現を抑制する働きを持つことを示した.
Notchシグナリングと器官アイデンティティーの確立

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究(A)

Category: 特定領域研究(A)

Institution: 東北大学

1999 - 1999

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複眼原基と触角原基の一部でNotchシグナリングを活性化すると、その触角原基の一部にeyが発現し、異所的な複眼が誘導される.その時、胸の体節で発現するAntennapedia(Antp)遺伝子を同時に発現させると、複眼が翅に、触角の一部は中肢に変換する.Antpが翅と肢の特異性を付加する機構として二つの可能性がある.一つは、Antpが胸(T2)という体節全体のアイデンティティーを付加し、その後、たとえば背腹の情報などにより、翅と中肢の特異性が決定される可能性であり、もう一つは、Antpが翅と中肢の特異性をそれぞれ別個に付加する可能性である.そのどちらであるかを検討するために、様々な変異を加えたミュータントAntp蛋白を発現させ、翅と肢の誘導能を比較した.もし翅と肢の誘導に必要な機能部位が両者で異なる場合は、第2の可能性が支持される. その結果、野生型のAntp蛋白を、Notchシグナリングの活性化と共に発現させると、156匹の内およそ半数の個体で複眼が翅に変換し、26%の個体で触角から中肢への変換が認められたのに対して、Hox遺伝子間で良く保存されており、co-factorであるExd/Pbx1蛋白が結合する、4種のアミノ酸の配列、YPWMモチーフをアラニンに置換したミュータント蛋白を発現させると、517匹の内、複眼から翅への変換を示した個体は一匹も観察されなかった。一方、およそ20%の個体が、触角から中肢への変換を示した.この結果は、Antp蛋白のYPWMモチーフは、翅のアイデンティティーの決定に必要であるが、中肢の決定には必要ではないことを示している.したがって、Antpは同一体節内において翅と中肢の決定にそれぞれ別個に関わり、翅の決定にはYPWMモチーフが重要な役割を果たしていることが明らかとなった.
The common mechanisms for the determination of organ identity

KURATA Shoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: TOHOKU UNIVERSITY

1998 - 1999

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The Notch signaling pathway defines an evolutionarily conserved cell-cell interaction mechanism that throughout development controls the ability of precursor cells to respond to developmental signals. Here we show that Notch signaling regulates the expression of the master control genes eyeless, vestigial, and Distal-less, which in combination with homeotic genes induce the formation of eyes, wings, antennae, and legs. Therefore, Notch is involved in a common regulatory pathway for the determination of the various Drosophila appendages.
Notchシグナリングを中心とした動物appendage形成の基本的共通機構

倉田祥一郎

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究(A)

Institution: 東北大学

1998 - 1998

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これまでに研究代表者は、ショウジョウバエで強制的にNotchシグナリングを活性化すると、その場所に、複眼の形成を支配するeyeless(ey)が新たに発現し、本来は存在しない複眼が形成される事、そして、逆に、複眼原基に元来存在するNotchシグナリングを遮断すると、ey遺伝子の発現がなくなり、複眼が形成されない事を明らかにしている。さらに、同様にNotchシグナリングを活性化しても、ey-のミュータントバックグランドでは、複眼のかわりに触角が形成される事を見い出している。これらの結果は、複眼と触角の形成時に共通して、Notchシグナリングがそれらの器官形成を支配するマスターコントロール遺伝子の発現を制御していることを示唆している。そこで、本研究では、触角の形成を支配するDistal-less(Dll)遺伝子に着目し、ey-のバックグランドで、Notchシグナリングを活性化した際、eyのかわりにDllが発現するかどうか調べた。その結果、ey-のバックグランドの複眼原基で、Notchシグナリングを活性化すると、本来は発現がみられないDllが発現するようになることを明らかにした。さらに、触角の原基に元来存在するNotchシグナリングを遮断すると、Dllの発現がなくなり、触角が形成されない事を明らかにした。これにより、複眼と触角の形成には、Notchシグナリングがそれぞれのマスターコントロール遺伝子の発現を制御するという基本的な共通機構が存在する事が明らかとなった。
昆虫複眼のマスターコントロール遺伝子eyelessの発現制御機構

倉田祥一郎

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 特定領域研究(A)

Institution: 東北大学

1998 - 1998

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ショウジョウバエのeyeless(cy,Drosophila Pax6)遺伝子は、昆虫の複眼形成を支配するマスターコントロール遺伝子である。したがって、複眼形成の機構を理解するためには、どのようにして正しい場所にそして正しい時期に、ey遺伝子の発現がおこるのか、その制御機構を知る事が極めて重要である。これまでに研究代表者は、Notchシグナリングがey遺伝子の発現を制御していることを明らかにしている。そこで本研究では、Notchシグナリングがどのように活性化されてey遺伝子が発現するのか、そのシグナリングのカスケードに着目して解析した。Notchレセプターの二つのリガンド、Delta(Dl)とSerrate(Ser)の関与を調べるために、それぞれのドミナントネガティブとして働くDlS、SerSをそれぞれ複眼原基で発現させたところ、複眼が形成されず、複眼形成時にDlとSerがNotchレセプターを活性化し、複眼形成を誘導することが明らかとなった。さらに、Notchシグナリングの制御因子であるSu(H)の関与を調べるために、複眼原基にSu(H)のミュータントクローンを誘導し、そのクローンにおけるey遺伝子の発現を調べたところ、ey遺伝子の発現が消失し、ey遺伝子の発現にSu(H)遺伝子が必要であることが明らかとなった。したがって、複眼形成時にはDIとSerがNotchレセプターを活性化し、その後Su(H)を介して、ey遺伝子の発現が誘導されることが明らかとなった。
Defense mechanism of insect (Sarcophaga peregrina)

NATORI Shunji, KURATA S, KUBO T

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Specially Promoted Research

Category: Grant-in-Aid for Specially Promoted Research

Institution: University of Tokyo

1992 - 1994

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Insect have developed a unique defense system against various outside stimuli such as microbial infection and integmental injury. We have been studying various defense proteins of Sarcophaga peregrina (the flesh fly). These proteins include a lectin and several antibacterial proteins. Throughout these studies, we came to the conclusion that there are two important novel aspects of these defense proteins. One is that a single defense protein probably plays at least two roles in defense and development. Insects probably have the flexibility to use one defense protein in multiple ways. The other interesting aspect is the phylogenetical significance of the insect defense system. Insect defense system is possibly a prototype of the mammalian defense system. Except these two important aspects, we obtained various important findings on insect immnity. Most of these findings have been published.
センチニクバエ蛹化時における自己細胞と自己由来非自己細胞の識別機構

倉田祥一朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業奨励研究(特別研究員)

Category: 奨励研究(特別研究員)

Institution: 東京大学

1990 - 1990

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昆虫が有する病原体認識システムの解明とその利用

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昆虫が有する病原体認識システムの解明とその利用の確立
自然免疫スクリーニングの多検体化とターゲット同定系の開発

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自然免疫スクリーニングの多検体化とターゲット同定系の開発
脳・神経系が産生する基本的生体防御機構の活性化因子

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脳・神経系が産生する基本的生体防御機構の活性化因子の解析
マスターコントロール遺伝子の発現制御機構を利用した器官．細胞改変技術の確立

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マスターコントロール遺伝子の発現制御機構を利用した器官．細胞改変技術の確立
器官アイデンティティー決定の基本的共通機構の解析

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器官アイデンティティー決定の基本的共通機構の解析
脳神経系が産生する Innate Immunity 活性化のメディエーター

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脳神経系が産生する Innate Immunity 活性化のメディエーターの解析
基本的生体防御システムの活性化機構

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基本的生体防御システムの活性化機構の解明
脳・神経系による生体防御系の活性化機構

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脳・神経系による生体防御系の活性化機構の解明

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