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The Kiss of Death: how the kinase, RIPK3, triggers cell killing by the pseudokinase, MLKL Event as iCalendar

18 September 2019

1 - 2pm

Venue: Mac 1 Biology Building

Location: 5 Symonds St

Host: SBS

Contact info: Assoc. Prof. Jane Allison

Contact email: j.allison@auckland.ac.nz

Dr James Murphy
Dr James Murphy

Speaker: Dr James Murphy, the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia


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 attributed roles in innate immunity, the pathogenesis of inflammatory diseases, and tissue injury arising from ischemic stroke or acute kidney injury. As a result, an improved fundamental knowledge of MLKL’s activation mechanism is of enormous interest as Dr James Murphy and colleagues, and others, look to target the pathway therapeutically.

Dr Murphy’s work has focused on the molecular mechanism underlying MLKL activation and how its cell killing function is regulated by its pseudokinase domain. Recently, his structural, biochemical, biophysical and cellular biology studies of MLKL activation have revealed a number of surprises, including an unexpected divergence in the mechanisms underlying the human and mouse necroptosis pathways, and the discovery of poxviral xenologs of MLKL that target the cellular necroptosis machinery to prevent cell death. 

The development of new tools has enabled Dr Murphy and colleagues to advance knowledge of the choreography of necroptotic cell death, and to identify new signalling checkpoints that could be therapeutically targeted.

For more information, please contact Assoc. Prof. Jane Allison, j.allison@auckland.ac.nz