Caspases and Inflammasomes in Innate Immunity

先天免疫中的半胱天冬酶和炎症小体

• 批准号: 2367792
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2367792
• 关键词: Caspases; Inflammasomes; Innate; Immunity

Inflammasomes mediate innate immunity to infection and trigger inflammation in hereditary syndromes by activating caspase-1. My group investigates (i) the mechanisms of activation of inflammasomes, (ii) the effector programmes orchestrated by caspases, and (iii) subversion of caspases by pathogens (ref 1-4). Many cellular and systemic effects of inflammasomes are brought about by poorly characterised substrates of caspase-1. We have been identifying and characterising new substrates of human caspases (ref 5). For example, we discovered UBE2L3 as a caspase-1 target, and the autophagy protein p62/SQSTM1 as a substrate of caspase-8 (ref 6). We are also interested in how bacteria subvert these pathways. For instance, we found that pathogenic E. coli inhibit caspase-4 in the gut (7). In this PhD project, the candidate will benefit from our open, collaborative and multidisciplinary approach to investigate the immune roles of exciting new candidate genes. I also have a Satellite Laboratory at The Francis Crick Institute, London where the candidate could network and access specialised facilities as and when necessary. Our funding sources include the MRC, Wellcome Trust, EPSRC and the Royal Society.

炎性小体通过激活caspase-1介导对感染的先天免疫并引发遗传性综合征的炎症。我的团队研究了(i)炎性小体的激活机制，（ii）由半胱天冬酶策划的效应程序，以及（iii）病原体对半胱天冬酶的破坏（参考文献1-4）。炎性小体的许多细胞和全身作用是由半胱天冬酶-1的不明确底物引起的。我们一直在鉴定和表征人类半胱天冬酶的新底物（参考文献5）。例如，我们发现UBE2L3是caspase-1的靶标，自噬蛋白p62/SQSTM1是caspase-8的底物（参考文献6）。我们也对细菌如何破坏这些途径感兴趣。例如，我们发现致病性大肠杆菌抑制肠道中的caspase-4(7)。在这个博士项目中，候选人将受益于我们开放、合作和多学科的方法来研究令人兴奋的新候选基因的免疫作用。我在伦敦的弗朗西斯·克里克研究所（Francis Crick Institute）也有一个卫星实验室，在那里，候选人可以在必要时联网并使用专门的设施。我们的资金来源包括MRC， Wellcome Trust， EPSRC和皇家学会。