Catalyst Awardee

Project Description

New strategy for general anesthetics development

Xuemei Chen, associate professor | Renji Hospital, School of Medicine, Shanghai Jiaotong University; Renji Hospital |  School of Medicine, Shanghai Jiaotong University 
Competition Sponsor:
 Chinese Academy of Medical Sciences
Awardee Year: 2023

 

General anesthetics (GA) has been widely used in many aspects of clinical settings, however, the specific mechanism and clear targets of them is still a mystery, which makes it difficult to develop more safe and efficient GA with fewer side effects. For the first time, we constructed a genome-wide general anesthetic target screening system basing on live animals. Under general anesthetics, nematodes displayed a rigid and stimulus unresponsive state, when introducing random point mutations into its genome, some mutant nematodes developed resistance to GA, indicating that the mutated gene is involved in the general anesthesia process. Here we completed gene mutagenesis of more than 100,000 nematodes and obtained 32 all anesthetic drug-insensitive mutant strains, and found two general anesthetic-related genes. Based on the previous work, we will further identify the remaining 30 mutant strains with all anesthesia-related genes, and the candidate proteins obtained from the screening would be structurally resolved by cryo-EM to find the exact binding site for GA, subsequently point mutation will be further constructed to verify the role of this molecular site in mammalian anesthesia, thus a new target for anesthetic drugs can be finally identified through the whole process. The screening of specific general anesthetic targets using this strategy will help us to walk out of the dilemma in the process of novel GA research and development, and hopefully drive the whole general anesthetic R&D related industry chain into a new high speed development channel.

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