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4月16日第二十七期水木清华生命科学讲座系列
发布时间:2015-04-02关键字:

第二十七期水木清华生命科学讲座系列

 

 

 
  邵峰博士1973年出生于江苏淮安,1996年毕业于北京大学技术物理系,2003年获得美国密西根大学医学院生物化学博士学位,现为北京生命科学研究所资深研究员、科研副所长。
  邵峰博士长期从事病原细菌和宿主相互作用的分子机理研究,近年来在对多种重要革兰氏阴性致病菌的毒力机制以及宿主抗细菌天然免疫防御方面取得了一系列重要原创性发现:在病原菌感染领域鉴定出多个病原菌毒力蛋白具有全新酶学活性,通过新的蛋白质翻译后修饰抑制宿主免疫防御;在抗细菌天然免疫研究中首次发现细菌内毒素、鞭毛蛋白以及病原菌三型分泌系统的胞内天然免疫受体,并鉴定出家族性地中海热自炎症疾病蛋白为天然免疫模式识别受体,感受病原菌对机体Rho蛋白的修饰和失活。这些系统性原创发现为抗感染药物和疫苗的研发提供了新思路并奠定了坚实的理论基础。邵峰博士在上述领域已发表学术论文50多篇,并获得多项国际和国内重要奖项,包括周光召基金会杰出青年基础科学奖、美国霍华德•休斯医学研究所国际青年科学家奖、国家杰出青年研究基金、国际蛋白质学会的青年科学家奖(鄂文西格青年科学家奖)以及吴阶平-保罗杨森基础医学奖等。



TOPIC:Innate immune sensing
of cytosolic bacteria and bacterial virulence

 
Speaker: Feng Shao, Ph.D.
Investigator and Associate Director
National Institute of Biological Sciences, Beijing
Abstract:
Canonical inflammasomes are cytoplasmic complexes that mediate caspase-1 activation, cytokine maturation and macrophage inflammatory death. We identify the NAIP family of NLR (Nucleotide-binding domain and Leucine-rich Repeat) proteins that are inflammasome receptors for bacterial flagellin as well as the needle and rod subunits of bacterial toxin-injecting type III secretion system (T3SS). Ligation of the NAIPs by the corresponding ligands promotes their physical association with an adaptor NLR protein NLRC4, resulting in caspase-1 activation and anti-bacteria defense. We also discover that Pyrin, encoded by the familial Mediterranean fever disease gene, forms a canonical inflammasome complex upon bacterial modifications/inactivation of host Rho proteins. These include glucosylation by Clostridium difficile cytotoxin TcdB, adenylylation by FIC-domain bacterial effectors, ADP-ribosylation by C. botulinum C3 toxin and deamidation by B. cenocepacia, which all occur in the switch I region in Rho-subfamily GTPases. The NAIP and Pyrin inflammasomes not only are important for inducing inflammation and restricting bacterial infections, but also serve as a mechanism for distinguishing pathogenic bacteria from non-pathogenic ones such as commensals. Lastly but most importantly, we demonstrate that inflammatory caspases including caspase-4/5 in human and caspase-11 in mice are cytosolic receptors for bacterial LPS (endotoxin). LPS directly binds to these caspases, leading to their oligomerization and catalytic activation, and eventually inflammatory cell death. In addition to a general role in anti-bacterial defense, caspase-4/5/11-mediated non-canonical inflammasome activation also critically determines Gram-negative bacteria-induced septic shock, providing an attractive new target for anti-sepsis drug development.
 
日期:2015年4月16日15:00-16:00
地点:医学科学楼B323
 

 




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