1:00pm, Monday, 21 November
Room BIG13, Ground Floor
710 Cumberland St
Prof. James Murphy
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia 3052
‘Licence to kill: understanding how the zombie protein, MLKL, is triggered to kill cells by necroptosis’
In 2012, Mixed lineage kinase domain-like (MLKL), a catalytically-dead (“zombie”) cousin of conventional protein kinases, termed a pseudokinase, was implicated as the key effector in the programmed necrosis (or necroptosis) cell death pathway. This pathway has been implicated in innate immunity, the pathogenesis of inflammatory diseases, and tissue injury arising from ischemia-reperfusion. As a result, an improved fundamental knowledge of MLKL’s activation mechanism is of enormous interest as we and others look to target the pathway therapeutically.
Here, I describe our recent work dissecting the chronology of events in this pathway using novel tools, structural biology, biochemistry, microscopy and proteomics. These studies have uncovered a series of regulated events that govern the pathway, raising the prospect that these checkpoints might be pharmacologically targetable for the treatment of inflammatory diseases, such as IBD.