Caspases and Inflammasomes in Innate Immunity

炎性小体介导对感染的先天免疫，并通过激活caspase-1触发遗传性综合征中的炎症。我的小组研究了（i）炎性小体激活的机制，（ii）由半胱天冬酶协调的效应程序，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效应是由胱天蛋白酶-1的特征性底物引起的。我们一直在鉴定和表征人半胱天冬酶的新底物（参考文献5）。例如，我们发现UBE 2L 3是半胱天冬酶-1的靶点，自噬蛋白p62/SQSTM 1是半胱天冬酶-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E.大肠杆菌抑制肠中的半胱天冬酶-4（7）。在这个博士项目中，候选人将受益于我们的开放，协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也有一个卫星实验室，候选人可以在必要时联网和访问专门的设施。我们的资金来源包括MRC，惠康信托，EPSRC和皇家协会。

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.