個人介紹:
李毓龍,beat365官方网站教授,北大-清華生命科學聯合中心、北京大學-IDG/麥戈文腦科學研究所研究員,博士生導師、國家傑出青年基金獲得者,新基石研究員。課題組聚焦于神經元通訊的基本結構——突觸,從兩個層面上開展研究工作:一是開發前沿的新型遺傳編碼的成像探針,用于在時間和空間尺度上解析神經系統的複雜功能;二是借助此類工具探究突觸傳遞的調節機制,特别是生理及病理條件下對神經遞質釋放的調控。李毓龍團隊先後開發了針對乙酰膽堿、單胺類、嘌呤類、脂類和神經肽類等神經調質的GRAB(GPCR activation-based)熒光探針,并成功用于多種模式動物的在體檢測。研究成果先後入選2018年及2023年中國生命科學十大進展,曾獲全國創新争先獎、談家桢生命科學獎、第二十屆吳階平-保羅·楊森醫學創新獎(吳楊獎)、首屆“科學探索獎”、首屆峰基金支持、教育部基礎學科拔尖學生培養計劃“優秀導師獎”等獎項。目前擔任Neuron雜志編輯委員會成員及National Science Review和Journal of Neurochemistry雜志編輯。
教育經曆:
2000-2006年,博士,神經生物學系,杜克大學
1996-2000年,學士,beat365,北京大學
工作經曆:
2020-今,教授,beat365,北京大學
2012-今,研究員,beat365,生命科學聯合中心,麥戈文腦研究所,北京大學
2019-2020年,副教授,beat365,北京大學
2012-2019年,助理教授,beat365,北京大學
2006-2012年,博士後,分子和細胞生理學系,斯坦福大學榮譽獎勵:
中國生命科學十大進展,2023
2022年度拜耳中國科研合作獎——拜耳研究員獎,2023
新基石研究員,2023
教育部基礎學科拔尖學生培養計劃“優秀導師獎”,2020
科學探索獎生命科學獎,2019
國家傑出青年科學基金,2019
第十二屆談家桢生命科學創新獎,2019
張香桐神經科學青年科學家獎,2019
第二十屆吳階平-保羅·楊森醫學藥學獎(吳楊獎),2019
中國十大醫學科技新聞,2018
中國生命科學十大進展,2018
中源協和生命醫學獎創新突破獎,2018
綠葉生物醫藥傑出青年學者獎,2015學術任職:
2023-今,Neuron,編委
2022-2024,美國神經科學學會,委員會成員
2022-今,National Science Review,編輯
2019-今,Journal of Neurochemistry,編輯
執教課程:
高級神經生物學
生命科學前沿文獻閱讀讨論
綜合科學實驗課程
遺傳學讨論課
神經生物學進展
現代生物學實驗技術原理及其應用
高級生物物理學
心理/神經/腦科學基礎 人的大腦由數十億的神經元組成,後者又通過數萬億的突觸組成複雜的神經網絡。不同種類的神經元經過或遠或近的投射,通過突觸與其他神經元進行信息交流,實現感知覺、決策和運動等高級神經功能。
研究大腦的最大挑戰在于腦的高度複雜性。我們實驗室集中在神經元通訊的基本結構突觸上,從兩個層面上開展研究:一是開發前沿的工具,即開發新型成像探針,用于在時間和空間尺度上解析神經系統的複雜功能;二是借助先進的工具探究突觸傳遞的調節機制,特别是在生理及病理條件下對神經遞質釋放的調節。
具體而言,對于工具開發,我們集中于:
1,結合光遺傳學和熒光成像,無損傷性的研究神經元之間的電突觸連接。電突觸的異常可導緻耳聾、癫痫、腦部腫瘤和心髒功能異常等疾病。
2,開發可遺傳編碼的檢測神經遞質/調質的熒光探針。神經遞質/調質是神經元化學突觸傳遞的關鍵介導分子,與感知、學習和記憶以及情緒密切相關。
利用上述熒光探針,我們的功能性和生理性的研究集中于:
1,結合雙光子成像和可遺傳編碼的熒光探針,使用果蠅和小鼠作為模式生物,研究嗅覺傳導或睡眠過程中腦的工作機制。
2,尋找上述新型化學遞質/調質小分子的對應受體,即尋找“孤兒”受體的配體。
3,結合生物信息學、分析化學、生物化學、生理學和成像學方法,系統地探索和鑒定潛在的新型小分子神經遞質。
Main research articles:
Xia, X., & Li, Y.* (2025) A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release. Nature Communications.
Yang J.#, Zhao, T.#, Fan, J.#, Zou, H.#, Lan, G., Guo, F., Shi, Y., Ke, H., Yu, H., Yue, Z., Wang, X., Bai Y., Li, S., Liu, Y., Wang, X., Chen, Y.*, Li, Y.*, & Lei, X.* (2024) Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch. Cell. Volume 187, Issue 25.
Lv, M., Cai, R., Zhang, R., Xia, X., Li, X., Wang, Y., Wang, H., Zeng, J., Xue, Y., Mao, L., & Li, Y.* (2024). An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning. National Science Review. 11(5): nwae112.
Umpierre, A. D.#*, Li, B.#, Ayasoufi, K., Simon, W. L., Zhao, S., Xie, M., Thyen, G., Hur, B., Zheng, J., Liang, Y., Bosco, D. B., Maynes, M. A., Wu, Z., Yu, X., Sung, J., Johnson, A. J., Li, Y.*, & Wu, L.-J.* (2024) Microglial P2Y6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis. Neuron. 112(12): 1959-1977. e10.
Feng, J.*, Dong, H., Lischinsky, J. E., Zhou, J., Deng, F., Zhuang, C., Miao, X., Wang, H., Li, G., Cai, R., Xie, H., Cui, G., Lin, D., & Li, Y.* (2024). Monitoring norepinephrine release in vivo using next-generation GRABNE sensors. Neuron. 112(12): 1930-1942. e6.
Deng, F.#, Wan, J.#, Li, G., Dong, H., Xia, X., Wang, Y., Li, X., Zhuang, C., Zheng, Y., Liu, L., Yan, Y., Feng, J., Zhao, Y., Xie, H., & Li, Y.*(2024). Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo. Nature Methods. 21(4): 692-702.
Zhuo, Y.#, Luo, B.#, Yi, X., Dong, H., Miao, X., Wan, J., Williams, J. T., Campbell, M. G., Cai, R., Qian, T., Li, F., Weber, S. J., Wang, L., Li, B., Wei, Y., Li, G., Wang, H., Zheng, Y., Zhao, Y., Wolf, M. E., Zhu, Y., Watabe-Uchida, M., & Li, Y.* (2024). Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo. Nature Methods. 10.1038/s41592-023-02100-w.
Wang, H.#, Qian, T.#, Zhao, Y., Zhuo, Y., Wu, C., Osakada, T., Chen, P., Chen, Z., Ren, H., Yan, Y., Geng, L., Fu, S., Mei, L., Li, G., Wu, L., Jiang, Y., Qian, W., Zhang, L., Peng, W., Xu, M., Hu, J., Jiang, M., Chen, L., Tang, C., Zhu, Y., Lin, D., Zhou, J.-N., & Li, Y.* (2023). A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors. Science, 382(6672), eabq8173.
Wu, Z.#, Cui, Y.#, Wang, H.#, Wu, H., Wan, Y., Li, B., Wang, L., Pan, S., Peng, W., Dong, A., Yuan, Z., Jing, M., Xu, M., Luo, M.*, & Li, Y.* (2023). Neuronal activity-induced, equilibrative nucleoside transporter-dependent, somatodendritic adenosine release revealed by a GRAB sensor. Proceedings of the National Academy of Sciences, 120(14), e2212387120.
Dong, H.#, Li, M.#, Yan, Y., Qian, T., Lin, Y., Ma, X., Vischer, H. F., Liu, C., Li, G., Wang, H., Leurs, R., & Li, Y.* (2023). Genetically encoded sensors for measuring histamine release both in vitro and in vivo. Neuron.
Zeng, J.#*, Li, X.#, Zhang, R., Lv, M., Wang, Y., Tan, K., Xia, X., Wan, J., Jing, M., Zhang, X., Li, Y., Yang, Y., Wang, L., Chu, J., Li, Y., & Li, Y.*. (2023). Local 5-HT signaling bi-directionally regulates the coincidence time window for associative learning. Neuron.
Qian, T.#, Wang, H.#, Wang, P.#, Geng, L., Mei, L., Osakada, T., Wang, L., Tang, Y., Kania, A., Grinevich, V., Stoop, R., Lin, D., Luo, M., & Li, Y.* (2023). A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments. Nature Biotechnology.
Wu, Z.*, He, K., Chen, Y., Li, H., Pan, S., Li, B., Liu, T., Wang, H., Du, J., Jing, M., & Li, Y.* (2021). A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo Neuron, 110(5), 770-782.e775.
Dong, A., He, K., Dudok, B., Farrell, J. S., Guan, W., Liput, D. J., Puhl, H. L., Cai, R., Wang, H., Duan, J., Albarran, E., Ding, J., Lovinger, D. M., Li, B., Soltesz, I., & Li, Y.*. (2021). A fluorescent sensor for spatiotemporally resolved imaging of endocannabinoid dynamics in vivo. Nature Biotechnology.
Wan, J., Peng, W., Li, X., Qian, T., Song, K., Zeng, J., Deng, F., Hao, S., Feng,J., Zhang, P., Zhang, Y., Zou, J., Pan, S., Shin, M., Venton, B. J., Zhu, J. J., Jing, M., Xu, M., Li, Y.*.(2021). A genetically encoded sensor for measuring serotonin dynamics. Nature Neuroscience, https://doi.org/10.1038/s41593-021-00823-7.
Qian, C., Wu, Z., Sun, R., Yu, H., Zeng, J., Rao, Y., & Li, Y. * (2021). Localization, proteomics, and metabolite profiling reveal a putative vesicular transporter for UDP-glucose. eLife, 10, e65417.
Sun, F.#, Zhou, J.#, Dai, B.#, Qian, T., Zeng, J., Li, X., Zhuo, Y., Zhang, Y., Wang, Y., Qian, C., Tan, K., Feng, J., Dong, H., Lin, D.*, Cui, G.*, & Li, Y.*.(2020). Next-generation GRAB sensors for monitoring dopaminergic activity in vivo. Nature Methods, https://doi.org/10.1038/s41592-020-00981-9.
Jing, M.*, Li, Y., Zeng, J., Huang, P., Skirzewski, M., Kljakic, O., Peng, W., Qian, T., Tan, K., Wu, R., Zhang, S., Pan, S., Xu, M., Li, H., Saksida, L. M., Prado, V. F., Bussey, T., Prado, M. A. M., Chen, L., Cheng, H., Li, Y.*.(2020). An optimized acetylcholine sensor for monitoring in vivo cholinergic activity. Nature Methods, https://doi.org/10.1038/s41592-020-0953-2.
Yu, H., Zhao, T., Liu, S., Wu, Q., Johnson, O., Wu, Z., Zhuang, Z., Shi, Y., He, R., Yang, Y., Sun, J., Wang, X., Xu, H., Zeng, Z., Lei, X., Luo, W.* & Li, Y.*. (2019). MRGPRX4 is a bile acid receptor for human cholestatic itch. eLife, 8, e48431.
Feng, J., Zhang, C., Lischinsky, J. E., Jing, M., Zhou, J., Wang, H., Zhang, Y., Dong, A., Wu, Z., Wu, H., Chen, W., Zhang, P., Zou, J., Hires, S. A., Zhu, J. J., Cui, G., Lin, D., Du, J. & Li, Y.* (2019). A Genetically Encoded Fluorescent Sensor for Rapid and Specific In Vivo Detection of Norepinephrine. Neuron, 102(4), 745-761.
Wu, Z.#, Feng, J.#, Jing, M., & Li, Y.* (2019). G protein-assisted optimization of GPCR-activation based (GRAB) sensors. Neural Imaging and Sensing 2019, vol. 10865, p. 108650N. International Society for Optics and Photonics.
Wu, L., Dong, A., Dong, L., Wang, S. Q., & Li, Y*. (2019). PARIS, an optogenetic method for functionally mapping gap junctions. eLife, 8, e43366.
Sun, F.#, Zeng, J.#, Jing, M.#, Zhou, J., Feng, J., Owen, S., Luo, Y., Li, F., Wang, H., Yamaguchi, T., Yong, Z., Gao, Y., Peng, W., Wang, L., Zhang, S., Du, J., Lin, D., Xu, M., Kreitzer, A. C., Cui, G. & Li, Y.* (2018). A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice. Cell, 174(2), 481-496.
Jing, M.#, Zhang, P.#, Wang, G., Feng, J., Mesik, L., Zeng, J., Jiang, H., Wang, S., Looby, J. C., Guagliardo, N. A., Langma, L. W., Lu, J., Zuo, Y., Talmage, D. A., Role, L. W., Barrett, P. Q., Zhang, L. I., Luo, M., Song, Y., Zhu, JJ* & Li, Y*. (2018). A genetically-encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nature Biotechnology, 36(8), 726-737.
Reviews, Book Reviews and Highlights
Qian, T., Wang, H., Xia, X., & Li, Y.# (2023) Current and emerging methods for probing neuropeptide transmission. Current Opinion in Neurobiology, 81, 102751.
Dong, C.#, Zheng, Y.#, Long-Iyer, K., Wright, E. C., Li, Y.*, & Tian, L.* (2022). Fluorescence imaging of neural activity, neurochemical dynamics, and drug-specific receptor conformation with genetically encoded sensors. Annual Review of Neuroscience.
Wu, Z., Lin, D., & Li, Y.* (2022). Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nature Reviews Neuroscience.
Zhuo, Y., Li, Y.* (2022). New imaging methods for monitoring dopaminergic neurotransmission. Science China Life Sciences, 65.
Yulong Li. (2021). Neuron, 109(21), 3346-3348.
Yu, H., Wangensteen, K., Deng, T., Li, Y., & Luo, W.* (2021). MRGPRX4 in Cholestatic Pruritus. Semin Liver Dis41(03), 358-367.
Wan, J. & Li, Y.* (2020). Recent Advances in Detection Methods for Neurotransmitters. Chinese Journal of Analytical Chemistry, 48(3), 307-315. (In Chinese)
Wu, Z.* & Li, Y.* (2020). New frontiers in probing the dynamics of purinergic transmitters in vivo. Neuroscience Research, https://doi.org/10.1016/j.neures.2020.01.008.
Zeng, J., Sun, F., Wan, J., Feng, J. & Li, Y.* (2019). New optical methods for detecting monoamine neuromodulators. Current Opinion in Biomedical Engineering, https://doi.org/10.1016/j.cobme.2019.09.010.
Jing, M., Zhang, Y., Wang, H. & Li, Y.* (2019). GPCR‐based sensors for imaging neurochemicals with high sensitivity and specificity. Journal of Neurochemistry, https://doi.org/10.1111/jnc.14855.
Dong, A.*, Liu, S., & Li, Y.* (2018). Gap Junctions in the Nervous System: Probing Functional Connections Using New Imaging Approaches. Frontiers in Cellular Neuroscience, 12, 320.
Wang, H., Jing, M., & Li, Y.* (2018). Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators. Current Opinion in Neurobiology, 50, 171-178.
Wang, A.#, Feng, J.#, Li, Y.*, & Zou, P.* (2018). Beyond Fluorescent Proteins: Hybrid and Bioluminescent Indicators for Imaging Neural Activities. ACS chemical neuroscience, 9(4), 639-650.
Qian, C., & Li, Y.* (2015). Spine maturation and pruning during development: Cadherin/Catenin complexes come to help. Science China. Life sciences,58(9), 929.
Li, Y.*, & Rao, Y.* (2015). Pied Piper of Neuroscience. Cell, 163(2), 267-268.