Posted: 18th December 2020
Dr John Scott, Leader of the Neurometabolism Team in SVI’s Protein Chemistry & Metabolism Unit, has been awarded both an NHMRC Ideas Grant and an ARC Discovery Project for his work on the enzyme Ca2+-calmodulin-dependent protein kinase kinase-2 (CaMKK2).
CaMKK2 is a key regulator of energy metabolism and is emerging as a potential target for a spectrum of psychiatric disorders, including anxiety, bipolar disorder and schizophrenia.
John’s funding from the ARC will allow the team, including SVI collaborators A/Prof Jon Oakhill and Prof Bruce Kemp, to examine in molecular detail how CaMKK2 helps the cell to sense and respond to changes in energy availability.
His NHMRC’s Ideas Grant, with Prof Andrew Gundlach from the Florey Institute and Prof Greg Steinberg from McMaster University in Canada, is focused particularly on the role of CaMKK2 in bipolar disorder.
Bipolar disorder is a severe, recurrent, lifelong mental illness that is a major cause of disability in Australia and worldwide.
John says that the disease burden and consequent high mortality rate of the condition has remained unchanged for more than 60 years.
“This reflects a continued failure to develop new targeted treatments to improve patient outcomes,” he says.
The cornerstone therapy for bipolar disorder remains drugs that were discovered, by chance, to be useful; these drugs are only modestly effective and tend to be poorly tolerated. A lack of understanding of the underlying molecular cause of the disorder means there are no rationally designed treatments.
“However, it is now becoming clear that the manic and depressive phases of bipolar disorder are triggered by imbalances in brain energy metabolism,” he says.
Previous work has shown that mutations which stop the normal function or availability of CaMKK2 are associated with bipolar disorder and there is other evidence to suggest that CaMKK2 would be a good target as a treatment for the disorder.
John’s team will be working with a mouse model to learn more about the molecular cause of bipolar disorder, and they have generated small molecules - potential drugs - that affect CaMKK2 function.
This funding puts him a step closer to his goal of understanding how CaMKK2 works, with a longer term aim of developing safer and more effective therapies for debilitating mental disorders.