当前位置:首页  数据  信息推荐  日历活动  学术

【生研院】特别邀请报告:Gad Frankel 教授(英国帝国理工学院)学术报告

时间:2017年11月03日 访问次数:15

报告题目:Citrobacterrodentiuminfection re-programmes metabolism in intestinal epithelial cellsin vivo
报告人:
Gad Frankel 教授
主持人:朱永群 教授
时   间:2017年11月7日(周二)下午3点
地   点:纳米楼457报告厅
报告人简介:

Gad Frankel教授是英国帝国理工学院(Imperial College London)生命科学系以及分子细菌学与细菌感染MRC研究中心的教授。Gad Frankel于1982年获得以色列耶路撒冷希伯来大学生物学学士学位,1988年在耶路撒冷希伯来大学获得遗传学博士学位,之后在美国斯坦福大学进行博士后研究,1992年进入以色列著名的魏茨曼科学研究所工作,1998年加入英国帝国理工学院,2002获得终身教授职位。

Gad Frankel博士主要通过细菌遗传学方法和小鼠感染模型来研究病原菌感染过程中效应蛋白的生物学功能,主要针对人类重要病原菌,包括肠致病型大肠杆菌(enteropathogenic E.coli, EPEC)、出血性大肠杆菌(enterohaemorrhagicE.coli, EHEC),沙门氏菌(Salmonella typhimurium)等。2002年至今,Gad Frankel博士在Naure、Cell Metabolism、NatureCommunications、PLOS Pathogens等上已经发表了百余篇重要研究论文,并且在Nature Review of Microbiology、 Current Opinion in Microbiology,、Trends in Microbiology等著名综述期刊上发表十余篇综述文章。

报告摘要:

The intestinal epithelial cells (IECs) form a robust line of innate host defence against ingested pathogens. IECs express a number of pattern recognition receptors (PRRs; e.g. TLR2 and TLR4), which enable the detection of pathogen-associated molecular patterns (PAMPs). As such, the pathogen - IEC interface constitutes the battle line between the host innate immune system and the pathogen’s counteracting virulence factors. We used the mouse pathogen Citrobacter rodentium, a model organism to study the human pathogens enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC), to investigate the impact of enteric infections on IEC metabolism, using global proteomic and targeted metabolomics and lipidomics. We found that C. rodentium infection results in repression of oxidative phosphorylation and a switch towards aerobic glycolysis. Consistently, there was a significant reduction in the levels of mature cardiolipins, lipids essential for generating the electrochemical gradient used for ATP production in the mitochondria. Concomitantly, the abundance of Gatm (glycine amidinotransferase), which utilises L-arginine as a substrate, was significantly elevated in infected IECs, leading to elevated levels of phosphocreatine that could efficiently distribute energy to subcellular sites. Using bioluminescent reporter strains we found that infection with wild type C. rodentium leads to increased oxygenation of the intestinal mucosal surface, supporting C. rodentium oxidative metabolism in vivo and reducing the abundance of obligate anaerobic commensals. Additionally, IECs responded to infection by activating Srebp2 and the cholesterol biosynthetic pathway (e.g. HMG-CoA reductase). Unexpectedly, infected IECs simultaneously up-regulated the cholesterol efflux proteins AbcA1 and AbcG8, as well as ApoA1 (involved in reverse cholesterol transport), resulting in higher levels of fecal cholesterol and a bloom of proteobacteria. These results suggest that C. rodentium manipulates host metabolism to evade innate immune responses (e.g. exposure to NO) and to establish a favourable gut ecosystem.


网址链接:http://lsi.zju.edu.cn/redir.php?catalog_id=43812&object_id=79014