Updated on 2022/05/21

写真a

 
Ei'ichi Iizasa
 
Organization
Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Social and Behavior Medicine Assistant Professor
Title
Assistant Professor
Profile
結核菌感染防御、ITAM関連シグナル伝達

Degree

  • Doctor (Agriculture) ( 2010.3   Kagoshima University )

Research Interests

  • yeast homologous recombination

  • ITAM

  • 脂質

  • 結核菌

  • パターン認識受容体

  • Gap repair cloning

  • pattern recognition receptor

  • immunology

Research Areas

  • Life Science / Plant molecular biology and physiology

  • Life Science / Immunology

  • Life Science / Molecular biology

Research History

  • Kagoshima University   Assistant Professor

    2022.4

  • Kagoshima University   Graduate School of Medical and Dental Sciences

    2015.1

  • Kagoshima University   Assistant Professor

    2003.4

Professional Memberships

  • 日本細菌学会

    2015.10

  • 日本インターフェロン・サイトカイン学会

    2015.10

  • 日本免疫学会

    2015.10

  • 日本農芸化学会

    2015.10

  • JAPAN SOCIETY FOR BIOSCIENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY

  • JAPANESE SOCIETY FOR BACTERIOLOGY

  • THE JAPANESE SOCIETY FOR IMMUNOLOGY

  • 日本インターフェロン・サイトカイン学会

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Papers

  • Ei'ichi Iizasa, Yasushi Chuma, Takayuki Uematsu, Mio Kubota, Hiroaki Kawaguchi, Masayuki Umemura, Kenji Toyonaga, Hideyasu Kiyohara, Ikuya Yano, Marco Colonna, Masahiko Sugita, Goro Matsuzaki, Sho Yamasaki, Hiroki Yoshida, Hiromitsu Hara .  TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation. .  Nature communications12 ( 1 ) 2299 - 2299   2021.4TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.

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    Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, a mechanism of action is unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2. Macrophages respond to glycosylated MA-containing lipids in a Mincle/FcRγ/CARD9-dependent manner to produce inflammatory cytokines and recruit inducible nitric oxide synthase (iNOS)-positive mycobactericidal macrophages. Conversely, macrophages respond to non-glycosylated MAs in a TREM2/DAP12-dependent but CARD9-independent manner to recruit iNOS-negative mycobacterium-permissive macrophages. Furthermore, TREM2 deletion enhances Mincle-induced macrophage activation in vitro and inflammation in vivo and accelerates the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts Mincle-FcRγ-CARD9-mediated anti-mycobacterial immunity. Mycobacteria, therefore, harness TREM2 for immune evasion.

    DOI: 10.1038/s41467-021-22620-3

    PubMed

  • Mio Kubota, Ei'ichi Iizasa, Yasushi Chuuma, Hideyasu Kiyohara, Hiromitsu Hara, Hiroki Yoshida .  Adjuvant activity of Mycobacteria-derived mycolic acids. .  Heliyon6 ( 5 ) e04064   2020.5Adjuvant activity of Mycobacteria-derived mycolic acids.

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    Successful vaccination, especially with safe vaccines such as component/subunit vaccines, requires proper activation of innate immunity and, for this purpose, adjuvant is used. For clinical use, alum is frequently used while, for experimental use, CFA, containing Mycobacterial components, was often used. In this report, we demonstrated that mycolic acids (MA), major and essential lipid components of the bacterial cell wall of the genus Mycobacterium, has adjuvant activity. MA plus model antigen-immunization induced sufficient humoral response, which was largely comparable to conventional CFA plus antigen-immunization. Importantly, while CFA plus antigen-immunization induced Th17-biased severe and destructive inflammatory responses at the injected site, MA plus antigen-immunization induced Th1-biased mild inflammation at the site. MA induced dendritic cell activation by co-stimulatory molecule induction as well as inflammatory cytokine/chemokine induction. MA plus antigen-immunization successfully protected mice from tumor progression both in prevention and in therapy models. We thus submit that MA is a promising adjuvant candidate material for clinical purposes and for experimental purposes from a perspective of animal welfare.

    DOI: 10.1016/j.heliyon.2020.e04064

    PubMed

  • Ishikawa A, Miyake Y, Kobayashi K, Murata Y, Iizasa S, Iizasa E, Yamasaki S, Hirakawa N, Hara H, Yoshida H, Yasaka T .  Essential roles of C-type lectin Mincle in induction of neuropathic pain in mice. .  Scientific reports9 ( 1 ) 872   2019.1Essential roles of C-type lectin Mincle in induction of neuropathic pain in mice.

  • Sasaguri T, Taguchi T, Murata Y, Kobayashi K, Iizasa S, Iizasa E, Tsuda M, Hirakawa N, Hara H, Yoshida H, Yasaka T .  Interleukin-27 controls basal pain threshold in physiological and pathological conditions. .  Scientific reports8 ( 1 ) 11022   2018.7Interleukin-27 controls basal pain threshold in physiological and pathological conditions.

  • Sayaka Iizasa, Ei'ichi Iizasa, Keiichi Watanabe, Yukio Nagano .  Transcriptome analysis reveals key roles of AtLBR-2 in LPS-induced defense responses in plants .  BMC Genomics18 ( 1 ) 995   2017.12Transcriptome analysis reveals key roles of AtLBR-2 in LPS-induced defense responses in plants

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    Publisher:BioMed Central Ltd.  

    Background: Lipopolysaccharide (LPS) from Gram-negative bacteria cause innate immune responses in animals and plants. The molecules involved in LPS signaling in animals are well studied, whereas those in plants are not yet as well documented. Recently, we identified Arabidopsis AtLBR-2, which binds to LPS from Pseudomonas aeruginosa (pLPS) directly and regulates pLPS-induced defense responses, such as pathogenesis-related 1 (PR1) expression and reactive oxygen species (ROS) production. In this study, we investigated the pLPS-induced transcriptomic changes in wild-type (WT) and the atlbr-2 mutant Arabidopsis plants using RNA-Seq technology. Results: RNA-Seq data analysis revealed that pLPS treatment significantly altered the expression of 2139 genes, with 605 up-regulated and 1534 down-regulated genes in WT. Gene ontology (GO) analysis on these genes showed that GO terms, "response to bacterium", "response to salicylic acid (SA) stimulus", and "response to abscisic acid (ABA) stimulus" were enriched amongst only in up-regulated genes, as compared to the genes that were down-regulated. Comparative analysis of differentially expressed genes between WT and the atlbr-2 mutant revealed that 65 genes were up-regulated in WT but not in the atlbr-2 after pLPS treatment. Furthermore, GO analysis on these 65 genes demonstrated their importance for the enrichment of several defense-related GO terms, including "response to bacterium", "response to SA stimulus", and "response to ABA stimulus". We also found reduced levels of pLPS-induced conjugated SA glucoside (SAG) accumulation in atlbr-2 mutants, and no differences were observed in the gene expression levels in SA-treated WT and the atlbr-2 mutants. Conclusion: These 65 AtLBR-2-dependent up-regulated genes appear to be important for the enrichment of some defense-related GO terms. Moreover, AtLBR-2 might be a key molecule that is indispensable for the up-regulation of defense-related genes and for SA signaling pathway, which is involved in defense against pathogens containing LPS.

    DOI: 10.1186/s12864-017-4372-4

    Scopus

    PubMed

  • Ei'ichi Iizasa, Takayuki Uematsu, Yasushi Chuma, Hideyasu Kiyohara, Mio Kutobta, Masayuki Umemura, Goro Matsuzaki, Sho Yamasaki, Hiromitsu Hara .  Two distinct ITAM-coupled receptors recognize mycobacterial mycolic acid-containing lipids and differently regulate immune responses .  CYTOKINE100   26 - 27   2017.12

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    Publisher:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    Web of Science

  • Phongsisay V., Iizasa E., Hara H., and Yoshida Y. .  Pertussis toxin targets the innate immunity through DAP12, FcRγ, and MyD88 adaptor proteins. .  Immunobiology222 ( 4 ) 664 - 671   2017.4Pertussis toxin targets the innate immunity through DAP12, FcRγ, and MyD88 adaptor proteins.Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

  • Vongsavanh Phongsisay, Ei'ichi Ilizasa, Hiromitsu Hara, Hiroki Yoshida .  Pertussis toxin targets the innate immunity through DAP12, FcR gamma, and MyD88 adaptor proteins .  IMMUNOBIOLOGY222 ( 4 ) 664 - 671   2017.4Pertussis toxin targets the innate immunity through DAP12, FcR gamma, and MyD88 adaptor proteins

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    Publisher:ELSEVIER GMBH, URBAN & FISCHER VERLAG  

    Activation of the innate immunity by adjuvants, such as pertussis toxin (PTX), in the presence of autoreactive lymphocytes and antigen mimicry is sufficient to trigger autoimmunity. Toll-like, C-type lectin, and immunglobulin-like receptors play an important role in the innate immunity by sensing a variety of microbial products through several adaptor proteins, including MyD88, DAP12, and FcR gamma. This study investigated the interaction between PTX and innate immune components. The direct interactions between coated PTX and receptor-fusion proteins were examined using ELISA-based binding assays. Functionally, PTX-binding receptors could be classified into two groups: inhibition (DAP12-coupled TREM2, ITIM-bearing SIRP alpha, SIGNR1/SIGNR3/DCSIGN) and activation (MyD88-associated TLR4, DAP12-coupled LMIR5/CD300b, FcR gamma-coupled LMIR8/CD300c, CLEC9A, MGL-1). DAP12, MyD88, and FcR gamma were selected for further investigation. A comprehensive analysis of gene transcription showed that PTX up regulated the expression of various inflammatory mediators. DAP12 deficiency resulted in reduction or enhancement of inflammatory responses in a cytokine-specific manner. PTX was able to activate the TREM2-DAP12 signalling pathway. PTX induced lower expression of inflammatory mediators in the absence of FcR gamma alone and substantially lost its inflammatory capacity in the absence of both FcR gamma and MyD88. PTX was able to activate the MyD88-NF-kappa B signalling pathway in the presence of TLR2 or TLR4. The inflammatory activity of PTX was completely lost by heating. These results demonstrate that PTX targets the innate immunity through DAP12, FcR gamma, and MyD88 providing new insights into the immunobiology of PTX. (C) 2016 Elsevier GmbH. All rights reserved.

    DOI: 10.1016/j.imbio.2016.12.004

    Web of Science

    PubMed

  • Iizasa S., Iizasa E., Matsuzaki S., Tanaka H., Kodama Y., Watanabe K., and Nagano Y. .  Arabidopsis LBP/BPI related-1 and -2 bind to LPS directly and regulate PR1 expression .  Scientific reports   2016.6Arabidopsis LBP/BPI related-1 and -2 bind to LPS directly and regulate PR1 expressionReviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

  • Uematsu T, Iizasa E, Kobayashi N, Yoshida H, Hara H. .  Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity. .  Scientific reports   2015.12Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity.Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

  • 永野幸生、飯笹英一 .  相同組換えで色々できちゃうDNAクローニング .  生物工学会誌   2015.10相同組換えで色々できちゃうDNAクローニングInvited Reviewed

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

  • Phongsisay V, Iizasa E, Hara H, Yoshida H. .  Evidence for TLR4 and FcRγ-CARD9 activation by cholera toxin B subunit and its direct bindings to TREM2 and LMIR5 receptors. .  molecular immunology   2015.5Evidence for TLR4 and FcRγ-CARD9 activation by cholera toxin B subunit and its direct bindings to TREM2 and LMIR5 receptors.Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.

  • Phongsisay V., Iizasa E., Hara H., and Yamasaki S. .  3-O-sulfo-β-d-galactose moiety of endogenous sulfoglycolipids is a potential ligand for immunoglobulin-like receptor LMIR5 .  Molecular immunology63 ( 2 ) 595 - 599   2015.23-O-sulfo-β-d-galactose moiety of endogenous sulfoglycolipids is a potential ligand for immunoglobulin-like receptor LMIR5Reviewed

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

  • Phongsisay V., Iizasa E., Hara H., and Yamasaki S .  LMIR5 extracellular domain activates myeloid cells through Toll-like receptor 4 .  Molecular immunology62   169 - 177   2014LMIR5 extracellular domain activates myeloid cells through Toll-like receptor 4Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

  • Yasukawa S., Miyazaki Y., Yoshii C., Nakaya M., Ozaki N., Toda S., Kuroda E., Ishibashi K., Yasuda T., Natsuaki Y., Mi-ichi F., Iizasa E., Nakahara T., Yamazaki M., Kabashima K., Iwakura Y., Takai T., Saito T., Kurosaki T., Malissen B., Ohno N., Furue M., Yoshida H., and Hara H*. .  An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells .  Nature Communications5   3755   2014An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cellsReviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

  • Iizasa E., Mitsutomi M., and Nagano Y .  Direct binding of a plant LysM receptor-like kinase, LysM RLK1/CERK1, to chitin in vitro .  Journal of Biological Chemistry285   2996 - 3004   2010.1Direct binding of a plant LysM receptor-like kinase, LysM RLK1/CERK1, to chitin in vitroReviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

  • Hara H.,Iizasa E., Nakaya M., and Yoshida H. .  L-CBM signaling in lymphocyte development and function, .  Journal of Blood Medicine1   93 - 104   2010.1L-CBM signaling in lymphocyte development and function,Reviewed

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  • Nagano Y., Takao S., Kudo T., Iizasa E., and Anai T .  Yeast-based recombineering of DNA fragments into plant transformation vectors by one-step transformation .  Plant Cell Reports26   2111 - 2117   2007Yeast-based recombineering of DNA fragments into plant transformation vectors by one-step transformationReviewed

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  • Iizasa E. and Nagano Y. .  Highly efficient yeast-based in vivo DNA cloning of multiple DNA fragments and the simultaneous construction of yeast/ Escherichia coli shuttle vectors .  Biotechniques40   75 - 83   2006.1Highly efficient yeast-based in vivo DNA cloning of multiple DNA fragments and the simultaneous construction of yeast/ Escherichia coli shuttle vectorsReviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

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Books

  • 免疫ペディア〜101のイラストで免疫学・臨床免疫学に強くなる!

    飯笹 英一, 原博満(Keyword7 抗原認識とプロセシング)

    羊土社  2017.6 

Presentations

  • 飯笹 英一   結核菌脂質ミコール酸を認識するパターン認識受容体とその免疫制御  

    第43回 蛋白質と酵素の構造と機能に関する九州シンポジウム  2019.9 

  • 飯笹英一, 植松崇之, 清原秀泰, 中馬康志, 久保田未央, 三山英夫, 梅村正幸, 松崎吾朗, 山崎晶, 吉田裕樹, 原博満   結核菌脂質を認識するDAP12会合型ITAM関連受容体の免疫制御  

    第2回抗酸菌研究会  2017.11 

  • 原 博満, 飯笹 英一, 清原 秀泰, 中馬 康志, 梅村 正幸, 山崎 晶, 松崎 吾朗, 吉田 裕樹   アルツハイマー病脳内炎症の中核機構に迫る ITAM共役型受容体による抗酸菌脂質の認識と自然免疫応答の制御  

    Dementia Japan  2017.10  (一社)日本認知症学会

  • 笹栗 智子, 田口 徹, 村田 祐造, 小林 希美子, 飯笹 さやか, 飯笹 英一, 津田 誠, 平川 奈緒美, 原 博満, 吉田 裕樹, 八坂 敏一   IL-27による感覚閾値の調節  

    日本生理学雑誌  2019.2  (一社)日本生理学会

  • 飯笹 英一, 三山英夫, 豊永憲司, 原博満   ITAM-Card9経路のGM-CSF受容体シグナルへの関与  

    第84回インターフェロン・サイトカイン学会  2019.8 

  • Iizasa E, Uematsu T, Chuma Y, Kiyohara H, Kubota M, Umemura M, Matsuzaki G, Yamasaki S, Hara H   The function of a DAP12-associated receptor recognizing mycobacterial lipids  

    日米医学協力計画 抗酸菌専門部会 第52回日米合同部会  2018.3 

  • Iizasa E, Uematsu T, Chuma Y, Kiyohara H, Kubota M, Umemura M, Matsuzaki G, Yamasaki S, Hara H   Two distinct ITAM-coupled receptors recognize mycobacterial mycolic acid-containing lipids and differently regulate immune responses  

    The 5th Annual Meeting of the International Cytokine and Interferon Society  2017.10 

  • Iizasa E, Uematsu T, Chuma Y, Kiyohara H, Kubota M, Umemura M, Matsuzaki G, Yamasaki S, Hara H   Two ITAM-coupled receptors recognizing Mycobacterial mycolic acid-containing lipids and having the different roles  

    The 46th Annual Meeting of the Japanese Society for Immunology  2017.12 

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Awards

  • 第85回日本インターフェロン・サイトカイン学会学術集会

    2021.5   ベストプレゼンテーション賞 銅賞

  • 第2回抗酸菌研究会ベストプレゼンテーション賞

    2017.11  

    飯笹 英一

Research Projects

  • βcサイトカイン受容体のシグナル伝達におけるITAM-Card9経路の役割解明

    Grant number:20K07551  2020.4

    日本学術振興会   科学研究費助成事業 基盤研究(C)  基盤研究(C)

    飯笹 英一

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

  • キチンによるII型免疫応答の分子制御機構解明

    2019.1 - 2019.12

    biolegend Japan株式会社  LEGEND Research Grant Program 2018(後期) 

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    Authorship:Principal investigator 

    Grant amount:\500000

  • キチンによるII型免疫応答の分子制御機構解明

    2019.1 - 2019.12

    Biolegend株式会社  LEGEND Research Grant Program 2018(後期) 

    飯笹 英一

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  • Th2型免疫応答誘導に関わるキチン受容体およびシグナル分子の同定

    2017.4 - 2019.3

    科学研究費補助金  若手研究(B)

  • Th2型免疫応答誘導に関わるキチン受容体およびシグナル分子の同定

    2017.4 - 2019.3

    日本学術振興会  科学研究費助成事業 若手研究B 

    飯笹 英一

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  • 敗血症におけるTREM1Lの同定

    2015.12 - 2017.12

    GSKジャパン  GSKジャパン若手研究助成 

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    Grant type:Competitive

  • 敗血症におけるTREM1リガンドの探索

    2015.9 - 2017.3

    グラクソ・スミスクライン株式会社  2015年度GSKジャパン研究助成 

    飯笹 英一

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  • 哺乳類におけるキチン受容体の同定

    2015.4 - 2016.3

    民間財団等  笹川科学研究助成 

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    Grant type:Competitive

  • 結核菌を認識する新規骨髄系ITAMRの同定

    2014.4 - 2017.3

    科学研究費補助金  若手研究(B)

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    結核菌を認識する新規骨髄系ITAMRの同定

  • 自然免疫におけるCard9シグナル伝達経路の解明

    2011.4 - 2014.3

    科学研究費補助金  特別研究員(PD)研究奨励費

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    自然免疫におけるCard9シグナル伝達経路の解明

  • ロイシンリッチリピート受容体キナーゼとそのリガンドの相互作用機構の解明

    2007.4 - 2010.3

    科学研究費補助金  特別研究員(DC1)研究奨励費

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    ロイシンリッチリピート受容体キナーゼとそのリガンドの相互作用機構の解明

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Teaching Experience

  • 免疫学

    Institution:鹿児島大学

 

Social Activities

  • サイエンスカフェかごしま

    Role(s): Informant, Organizing member

    鹿児島大学若手教員サイエンスカフェ有志の会 

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    Type:Science cafe

    鹿児島大学若手教員サイエンスカフェ有志の会は、市民の方々に研究の話を気軽に楽しんでもらうサイエンスカフェを行うために、鹿児島大学の若手教員を中心に結成されました。私達、有志の会は、大体2ヶ月に1度のペースで、鹿児島市内のカフェでサイエンスカフェを開催しています。また、不定期に鹿児島県内の離島やその他の地域でもサイエンスカフェを行っています。