Cell signalling, Protein kinases and Pseudokinases
My lab studies the protein-protein interactions that underpin signal transduction. Much of our work is focused on understanding the molecular mechanisms by which protein kinases and their relatives, pseudokinases, regulate cell signalling.
Long considered the poor cousins of conventional protein kinases owing to their lack of catalytic activity, pseudokinases have emerged over the past decade as crucial components of signalling pathways across the kingdoms of life. To date there have been few detailed studies of members of the mammalian ‘pseudokinome’, but already it is evident that this protein family exhibits functional diversity consistent with their diverse evolutionary origins.
My lab has focused on the pseudokinase, MLKL, the most terminal (known) effector in the necroptosis cell death pathway. Detailed knowledge of MLKL activation, regulation and downstream activity has set the scene for therapeutic targeting of MLKL. This work provides a template for developing a detailed understanding of how the remaining ~50 uncharacterised pseudokinases modulate cell signalling.
Lab focus: cell signalling, protein kinases and pseudokinases
Our work is focused on understanding how proteins within cells interact, and how genetic mutations that perturb these interactions can cause disease.
We are particularly interested in interactions between proteins involved in cell signalling. The network of signalling proteins within cells can be likened to an electronic circuit. Our research is identifying the missing components in these ‘circuits’ and explaining how diseases are caused by defects in the circuit components.
By understanding how defective signalling causes disease, we aim to develop drugs to control the actions of defective components. In particular we are seeking to understand how signalling defects can lead to a range of diseases, including ischemia-reperfusion injuries, such as stroke and kidney injury, muscular dystrophy and cancers.
We are also assisting our colleagues at the Menzies Institute with the development of a vaccine for Tasmanian devil facial tumour disease.