On November 7, the team of Shao Zhenhua/Yan Wei from the State Key Laboratory of Biotherapy at West China Hospital of Sichuan University and Tianfu Jincheng Laboratory (Center of Frontier Medicine), together with the team of Sun Jinpeng/Yu Xiao from Shandong University, published their latest research paper in Nature.

       The research first systematically characterized the pharmacological efficacy of endogenous biogenic amines, clinical antipsychotic drugs, and psychoactive drugs such as amphetamine in activating multiple G-protein signaling pathways of the TAAR1 receptor. It discovered the plasticity of the drug recognition pocket within the TAAR1 receptor. Based on this new mechanism, new ligands targeting TAAR1 were screened and obtained, elucidating the different pathways through which TAAR1 activated the Gs/Gi signaling. It provided a crucial theoretical basis for the development of drugs targeting TAAR1.

       West China Hospital of Sichuan University's postdoctoral fellows Xu Zheng and Shen Siyuan, as well as doctoral students Yu Jingjing, Wu Chao, and Zhao Chang (a total of seven persons), served as the co-first authors of the paper. Researchers Shao Zhenhua and Yan Wei (a total of five persons) served as the co-corresponding authors of the paper. Besides, Wei Yuquan, an academician of the Chinese Academy of Sciences and Director of the State Key Laboratory of Biotherapy at West China Hospital of Sichuan University; Yang Shengyong, a professor of the State Key Laboratory of Biotherapy at West China Hospital of Sichuan University; and Wang Xiaohui, the leader of the medicinal chemistry and biology research team at Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, offered significant assistance to the research.

       It is worth noting that this is also the second paper in Nature published by Tianfu Jincheng Laboratory (Center of Frontier Medicine) this year.

       Researcher Dong Haohao and Associate Professor Tang Xiaodi's team from the State Key Laboratory of Biotherapy at West China Hospital of Sichuan University, together with Professor Zhang Xing's team from the Center of Cryo-Electron Microscopy at the School of Medicine, Zhejiang University and Professor Zhou Ruhong's team from the College of Life Sciences, Zhejiang University, published the research paper in Nature.

       The above-mentioned research captured multiple intermediate conformations of BAM and its substrate β-barrel protein EspP during outer membrane folding and integration for the first time and revealed the entire process of substrate OMP assembly, closure, and release through in vitro and in vivo functional analysis and all-atom molecular dynamics simulations. It provided a crucial basis for the R&D of new antibacterial drugs targeting this protein complex.

       Two papers were published consecutively in Nature within one year, and major scientific discoveries and breakthroughs were made in related fields, marking the phased progress of Tianfu Jincheng Laboratory (Center of Frontier Medicine) in academic accumulation, scientific research strength, and creativity.

                                                                                                      - By the responsible person of Tianfu Jincheng Laboratory

       Researcher Shao Zhenhua serves as the chief scientist and responsible person for the cryo-electron microscopy platform, one of the five major functional platforms initiated by the laboratory in the first batch. Dr. Zhao Jie serves as the technical director. It is equipped with high-end cryo-electron microscopes and provides one-stop structural biology, pharmacological research, and CRO services with the help of internationally cutting-edge technologies.

       Subsequently, the cryo-electron microscopy platform plans to establish a complete and reliable database of drug target protein structure and pharmacological information worldwide to continuously and efficiently facilitate the R&D and transformation of innovative drugs. It will establish a comprehensive talent introduction, cultivation, and management system according to the principle of "setting up posts as needed, selecting and employing personnel according to posts, classified management, and independent cultivation" to promote basic research and cultivate and attract outstanding talents at home and abroad.