Choreography of cell death by necroptosis

Choreography of cell death by necroptosis

Project details

The pseudokinase Mixed lineage kinase domain-like (MLKL) is the most terminal known obligate effector in the emerging cell death signalling pathway known as necroptosis. Recent data have implicated this pathway in pathological inflammation and ischemic reperfusion injuries and, as a result, MLKL has emerged as a novel therapeutic target.

It is currently unclear how MLKL is activated by its upstream regulators, the protein kinases RIPK1 and RIPK3, and how it induces cell death. This project aims to provide mechanistic insights into these important biological processes using structural, molecular and cellular biology and biochemical approaches. 

About our research group

The Murphy and Czabotar groups focus on understanding the molecular mechanisms of cell death by solving the structures of key proteins in cell death pathways and using these insights to interrogate their functions in vitro, in biochemical or cell-based studies. In particular, we have focused on understanding how MLKL is activated by the protein kinase RIPK3 (Murphy, Immunity 2013 39(3):443; Murphy, Biochem J 2014 457(3):369) and how MLKL kills cells (Hildebrand, PNAS 2014 111(42):15072).

 

Researchers:

Dr Peter Czabotar

Peter Czabotar
Dr
Peter
Czabotar
Laboratory Head

Dr James Murphy

Dr James Murphy looking at a 3D structure
Dr
James
Murphy
Laboratory Head
Dr Emma Petrie profile shot
Dr
Emma
Petrie
Cell Signalling and Cell Death division

Project Type: