【讲座题目】Gaucher disease protects against tuberculosis

【主讲人】范婧雯 博士（法国巴斯德研究所）

【时间】2023年9月4日（周一）下午15:00

【地点】伟德BETVlCTOR1946 E307学术报告厅

【邀请人】韩家淮 教授

【主讲人介绍】范婧雯，法国巴斯德研究所博士后。2017年毕业于伟德BETVlCTOR1946，获学士学位。2022年毕业于剑桥大学，获博士学位。伟德国际官网登录入口博伊特勒书院首届拔尖班毕业生。先后获剑桥大学Gates Scholarship，巴斯德基金会Gillings Fellowship。

【报告摘要】Biallelic mutations in the glucocerebrosidase (GBA1) gene cause Gaucher disease, characterized by lysosomal accumulation of glucosylceramide and glucosylsphingosine in macrophages. Gaucher and other lysosomal diseases occur with high frequency in Ashkenazi Jews. It has been proposed that the underlying mutations confer a selective advantage, in particular conferring protection against tuberculosis. Here, using a zebrafish Gaucher disease model, we find that the mutation GBA1 N370S, predominant among Ashkenazi Jews, increases resistance to tuberculosis through the microbicidal activity of glucosylsphingosine in macrophage lysosomes. Consistent with lysosomal accumulation occurring only in homozygotes, heterozygotes remain susceptible to tuberculosis. Thus, our findings reveal a mechanistic basis for protection against tuberculosis by GBA1 N370S and provide biological plausibility for its selection if the relatively mild deleterious effects in homozygotes were offset by significant protection against tuberculosis, a rampant killer of the young in Europe through the Middle Ages into the 19th century.