Caspases and Inflammasomes in Innate Immunity

炎症体通过激活caspase-1介导对感染的先天免疫，并在遗传综合征中引发炎症。我的小组研究(I)炎性小体的激活机制，(Ii)由caspase编排的效应程序，以及(Iii)病原体对caspase的颠覆(参考文献1-4)。炎症小体的许多细胞和系统效应是由caspase-1特征不佳的底物引起的。我们一直在鉴定和表征人类半胱氨酸酶的新底物(参考文献5)。例如，我们发现UBE2L3作为caspase-1的靶标，自噬蛋白p62/SQSTM1作为caspase-8的底物(参考文献6)。我们还对细菌如何颠覆这些途径感兴趣。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的开放、协作和多学科方法来研究令人兴奋的新候选基因的免疫作用。我在伦敦弗朗西斯·克里克研究所也有一个卫星实验室，候选人可以在那里建立网络，并在必要时使用专门的设施。我们的资金来源包括MRC、Wellcome Trust、EPSRC和皇家学会。

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.