Jean-Luc Imler-蔡华实验室

（Jean-Luc Imler-Cai Lab）

1. 负责人简介（Introduction of Team Leader）

Jean-Luc Imler

Jean-Luc Imler 教授,博士生导师，法国科学院分子细胞生物学研究所所长，法国享受盛誉的法国科学院银质奖章获得者，国家"高等学校学科创新引智计划" (简称"111计划") 项目的法方核心成员之一，获得2015年法国研究所基金会雅菲奖，中法霍夫曼免疫研究所果蝇抗病毒天然免疫课题组长。Jean-Luc Imler 教授1994年进入法国国家科学研究院分子生物细胞研究所工作至今。曾任法国国家科学院评审团成员，2013年出任UPR9022研究中心主任，2018年成为分子生物细胞研究所所长。

Jean-Luc Imler教授是果蝇抗病毒免疫研究的重要开拓者，对该领域做出了一系列原创性的贡献：1）首次在果蝇中揭示RNAi是广谱的抗病毒机制（Galiana-Arnoux et al, 2006, Nature Immunol；Mueller et al, 2010, PNAS；Kemp et al, 2013, J Immunol）；2）发现宿主因子RACK1和钾离子通道等果蝇和人类病毒感染中的作用（Eleftherianos et al , 2011,PNAS；Majzoub et al, 2014, Cell）；3）诱导性的抗病毒信号通路，包括Jak-STAT在抵抗果蝇病毒感染的作用Dostert et al, 2005, Nature Immunol; Deddouche et al, 2008, Nature Immunol ; Lamiable et al , 2016, PNAS ; Goto et al, 2018, Immunity)。首次揭示果蝇中cGLR1/2-cGAMP-STING信号通路识别病毒感染及其机制，改变了以往认为RNA干扰是果蝇唯一广谱抗病毒机制的认识（Hua et al,2020, Sci Signal; Andreas, et al,Nature,2021; Slavik, Nature, 2021）。截止目前，已在Nature，Cell，Nature Immunology，Immunity，Nature Genetics，PNAS，Journal of immunology，Journal of virology等权威杂志发表论文87篇。担任Nature Reviews Immunology, Nature Immunol., Immunity, Current Opinion journals等期刊审稿人。在国际会议上受邀做了100多次汇报。目前结合遗传学，高通量测序和成像技术研究新的抗病毒机制。多次组织国际性会议，包括Integrated insect immunology和controlling infections等。

Prof. Jean-Luc Imler, PhD supervisor, Director of the Institute of Molecular Cell Biology of the French Academy of Sciences, recipient of the Silver Medal of the French Academy of Sciences, one of the core members of the National Program for the Introduction of Innovation in Higher Education (111 Program), recipient of the 2015 Jaffe Prize of the French Research Foundation, Director of the Drosophila Antiviral Natural Immunity Group of the Hoffmann Institute of Immunology in France and China. Prof. Jean-Luc Imler joined the Institute of Molecular Biology and Cellular Research of the Institut National de la Recherche Scientifique (INRS) in 1994 and has been working there since then. He was a member of the jury of the French National Academy of Sciences, became Director of the UPR 9022 Research Center in 2013 and Director of the Institute for Molecular Biology and Cellular Research in 2018.

Prof. Jean-Luc Imler is an important pioneer in the study of antiviral immunity in Drosophila and has made a series of original contributions to the field: 1) first revealing in Drosophila that RNAi is a broad-spectrum antiviral mechanism (Galiana-Arnoux et al, 2006, Nature Immunol; Mueller et al, 2010, PNAS; Kemp et al, 2013, J Immunol); 2) discovery of a role for host factor RACK1 and potassium channels in Drosophila and human viral infections (Eleftherianos et al , 2011,PNAS; Majzoub et al, 2014, Cell); 3) inducible antiviral signaling pathways, including Jak-STAT in resistance to Drosophila virus infection Dostert et al, 2005, Nature Immunol; Deddouche et al, 2008, Nature Immunol ; Lamiable et al , 2016, PNAS ; Goto et al, 2018, Immunity) . The cGLR1/2-cGAMP-STING signaling pathway in Drosophila was revealed for the first time to recognize viral infection and its mechanism, changing the previous understanding that RNA interference is the only broad-spectrum antiviral mechanism in Drosophila (Hua et al, 2020, Sci Signal; Andreas, et al, Nature, 2021; Slavik, Nature , 2021). Up to now, he has published 87 papers in prestigious journals such as Nature, Cell, Nature Immunology, Immunity, Nature Genetics, PNAS, Journal of immunology, and Journal of virology. He is a reviewer for Nature Reviews Immunology, Nature Immunol., Immunity, Current Opinion journals and other journals. He has been invited to give more than 100 presentations at international conferences. He is currently working on novel antiviral mechanisms combining genetics, high-throughput sequencing and imaging technologies. He has organized several international conferences including Integrated insect immunology and controlling infections.

蔡华研究员

蔡华，研究员，毕业于中科院广州生物医药与健康研究院，曾在法国国家科研中心分子细胞生物学研究所进行博士后研究。入选广州市高层次人才-优秀专家，广东省科学技术协会青年培育人才。研究方向为利用果蝇和哺乳动物细胞研究病毒核酸与模式识别受体结合诱导的抗病毒天然免疫。从宿主和病毒两个角度开展研究：宿主方面，利用果蝇和哺乳动物细胞研究病毒组分与模式识别受体结合诱导的抗病毒天然免疫及其进化；病毒方面，通过鉴定病毒编码的新组分，发现宿主识别病毒感染的新机制。解决了长期以来业界对昆虫如何识别病毒感染进而导致诱导性广谱抗病毒机制这一问题的困惑，国际顶级期刊Nature的news and views做了专门报道。在《Nature》, 《Science Signaling》，《Immunity》，《Journal of Virology》等知名期刊发表论文共12篇，累计影响因子超过173，受邀请在《Current Opinion in Immunology》，《Faculty Reviews》等重要杂志发表综述。主持国家自然科学基金，广东省自然科学基金等国家，省市校级项目共10项。

 Cai Hua, Researcher, he got his phD from Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences. He was selected as Guangzhou High-level talents - excellent expert and Youth Cultivation talents of Guangdong Association of Science and Technology. His research interest is to study the antiviral innate immunity induced by the interaction of viral nucleic acid (PAMPs) with pattern recognition receptor using Drosophila and Mammalian cells. One of his work commented by Nature News and Views, is regarding how insects recognize virus infection and then lead to an induced broad antiviral response. He has published 12 papers in Nature, Science Signaling, Immunity, Journal of Virology, mBio and other well-known journals with a cumulative impact factor more than 173. He published reviews in Current Opinion in Immunology and Faculty Review. He has hosted over 10 national, provincial and university-level projects, including the National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province, et al.

2. 课题组研究方向（Research interests）

病毒性传染病一直严重威胁人类健康。天然免疫是抵抗病毒感染的第一道防线，并且决定适应性免疫的走向。法国国家科学研究中心分子细胞生物学研究所的Jules Hoffmann教授是天然免疫的开拓者，其团队的Jean-Luc Imler教授是国际抗病毒天然免疫开拓者之一。Jean-Luc Imler教授发现了新的果蝇和人类保守抗病毒免疫机制，其课题组利用果蝇，小鼠和人类细胞等为模型，深入探索抗病毒天然免疫新的分子机制，为当下及未来开发新的抵抗病毒性传染病提供重要参考。

Viral infectious diseases have always been a serious threat to human health. Natural immunity is the first line of defense against viral infections and determines the course of adaptive immunity. Professor Jules Hoffmann of the CNRS Institute of Molecular Cell Biology is one of the pioneers of natural immunity and his team, Professor Jean-Luc Imler, is one of the international pioneers of natural immunity against viruses. His group has used Drosophila, mouse and human cells as models to explore new molecular mechanisms of antiviral natural immunity, which will provide important references for the development of new resistance to viral infectious diseases today and in the future.

3. 课题组代表文章（Selected publications）

1. Hua Cai, Lihua Li, Kailey Slavik, Jingxian Huang, Ting Yin, Léna Hédelin,Zhangmin Xiang, Yunyun Yang, Xiaoyan Li, Yuqiang Chen, Ziming Wei, Huimin Deng, Di Chen, Renjie Jiao, Nelson Martins, Carine Meignin, Philip Kranzusch，and Jean-Luc Imler； A novel virus-induced cyclic dinucleotide, 2′3′-c-di-GMP, mediates STINGdependent antiviral immunity in Drosophila.（投稿到Immunity，修回）

2. Hua Cai, Carine Meignin, Jean-Luc Imler; cGAS-like receptor-mediated immunity: the in sect perspective, Current Opinion in Immunology, 2022, 74: 183-189.

3.  Andreas Holleufer, Kasper Grønbjerg Winther, Hans Henrik Gad, Xianlong Ai, Yuqiang Chen, Lihua Li, Ziming Wei, Huimin Deng, Jiyong Liu, Ninna Ahlmann Frederiksen, Bine Simonsen, Line Lykke Andersen, Karin Kleigrewe, Louise Dalskov, Andreas Pichlmair, Hua Cai, Jean-Luc Imler, Rune Hartmann; Two cGAS-like receptors induce Sting-dependent antiviral immunity in Drosophila melanogaster, Nature, 2021 Sep; 597(7874):114-118.

4. Slavik KM, Morehouse BR, Ragucci AE, Zhou W, Ai X, Chen Y, Li L, Wei Z, Bähre H, König M, Seifert R, Cai H, Imler JL, Kranzusch P*. cGAS-like receptors control RNA sensing and 3’2’-cGAMP antiviral signaling in Drosophila. Nature, 2021 Sep;597(7874):109-113.

5. Hua Cai, Jean-Luc Imler*. cGAS-STING: insight on the evolution of a primordial antiviral signaling cassette. Faculty Reviews, 2021, 10: (54).

6. Pennemann FL, Mussabekova A, Urban C, Stukalov A, Andersen LL, Grass V, Lavacca TM, Holze C, Oubraham L, Benamrouche Y, Girardi E, Boulos RE, Hartmann R, Superti-Furga G, Habjan M, Imler JL, Meignin C, Pichlmair A. Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators. Nat Commun. 2021 Dec 1;12(1):7009.

7. Schneider J, Imler JL*. Sensing and signalling viral infection in drosophila. Dev Comp Immunol. 2021 Apr;117:103985. Epub 2020 Dec 23.

8. Hua Cai, Andreas Holleufer, Bine Simonsen, Juliette Schneider, Aurélie Lemoine, Hans Henrik Gad, Jingxian Huang, Jieqing Huang, Di Chen, Tao Peng, João T Marques, Rune Hartmann, Nelson E Martins, Jean-Luc Imler; 2 ' 3 '-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in Drosophila, Science Signaling, 2020, 13(660): eabc4537.

9. Goto A#*, Okado K#, Martins N, Cai H, Barbier V, Lamiable O, Troxler L, Santiago E, Kuhn L, Paik D, Silverman N, Holleufer A, Hartmann R, Liu J, Peng T, Hoffmann JA, Meignin C, Daeffler L, Imler JL*. The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila. Immunity. 2020 Jan 14;52(1):200.

10. Lamiable O, Kellenberger C, Kemp C, Troxler L, Pelte N, Boutros M, Marques JT, Daeffler L, Hoffmann JA, Roussel A & Imler JL (2016) “Cytokine Diedel and a viral homologue suppress deleterious IMDdependent gene expression in Drosophila” Proc. Natl. Acad. Sci. USA, 113: 698-703.

11. Majzoub K, Hafirassou ML, Meignin C, Goto A, Marzi S, Fedorova A, Verdier Y, Vinh J, Hoffmann JA, Martin F, Baumert TF, Schuster C, Imler JL. RACK1 controls IRES-mediated translation of viruses. Cell. 2014 Nov 20;159(5):1086-1095.

12. Kemp C, Mueller S, Goto A, Barbier V, Paro S, Bonnay F, Dostert C, Troxler L, Hetru C, Meignin C, Pfeffer S, Hoffmann JA, Imler JL. Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila. J Immunol. 2013 Jan 15;190(2):650-8.

13. Eleftherianos I, Won S, Chtarbanova S, Squiban B, Ocorr K, Bodmer R, Beutler B, Hoffmann JA, Imler JL. ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections. Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12024-9.

14. Mueller S, Gausson V, Vodovar N, Deddouche S, Troxler L, Perot J, Pfeffer S, Hoffmann JA, Saleh MC, Imler JL. RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila. Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19390-5.

15. Deddouche S, Matt N, Budd A, Mueller S, Kemp C, Galiana-Arnoux D, Dostert C, Antoniewski C, Hoffmann JA, Imler JL. The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila. Nat Immunol. 2008 Dec;9(12):1425-32.