Dr John W Scott
Leader, Neurometabolism Group
Exercise and Nutrition Research Program
Areas of expertise: Cell Signaling, Metabolic Regulation, Neuropharmacology
Phone: 03 9288 3632
Location: ACU Melbourne Campus
ORCID ID: 0000-0002-1896-9798
Dr Scott’s primary research interest is on understanding the molecular pathways that regulate mood and behaviour in response to hormones and metabolites that signal changes in nutrient availability caused by increased energy demand (exercise) and energy deprivation (starvation). His research is focused on the control of the CaMKK2 signalling pathway, which is a regulator of brain function and whole-body energy metabolism. Loss-of-function mutations in CaMKK2 are linked with bipolar disorder in humans, a devastating mental illness for which there are no targeted therapies. A major goal of Dr Scott’s research is to validate CaMKK2 as a rational treatment target for mood disorders, and he has established international collaborations with academic and industrial partners to develop new drugs that target CaMKK2.
Dr Scott graduated with a Bachelor of Science (Hons) from the University of Glasgow and a PhD in Biochemistry from the University of Dundee funded by a prestigious Wellcome Trust Prize scholarship. He moved to Melbourne in 2006 to undertake postdoctoral studies at St Vincent’s Institute of Medical Research (SVIMR) and established the Neurometabolism group at SVIMR in 2018. Dr Scott is also a Senior Honorary Research Fellow of the Florey Institute of Neuroscience and Mental Health, and a member of the Scientific Advisory Board of Siragen Pharmaceuticals (San Diego, USA). His group uses a wide range of techniques including biochemistry, cell biology, protein crystallography, mass spectrometry and genetically modified mouse models to decipher the role of the CaMKK2 pathway in the regulation of brain function and energy metabolism in health and disease.
- Asquith CRM, Godoi PH, Counago RM, Laitinen T, Scott JW, Langendorf CG, Oakhill JS, Drewry DH, Zuercher WJ, Koutentis PA, Willson TM and Kalogirou AS (2018). 1,2,6-Thiadiazinones as novel spectrum Calcium-calmodulin-dependent protein kinase 2 (CaMKK2) inhibitors. Molecules. 23, 1221.
- O’Brien MT, Oakhill JS, Ling NXY, Langendorf CG, Hoque A, Dite TA, Means AR, Kemp BE and Scott JW (2017). Impact of genetic variation on human CaMKK2 regulation by Ca2+-calmodulin and multi-site phosphorylation. Scientific Reports. 7, 43264.
- Scott JW, Park E, Rodriguiz RM, Oakhill JS, Issa SM, O'Brien MT, Dite TA, Langendorf CG, Wetsel WC, Means AR and Kemp BE (2015). Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder. Scientific Reports. 5, 14436.
- Scott JW, Galic S, Graham KL, Foitzik R, Ling NXY, Dite TA, Issa SM, Langendorf CG, Weng QP, Thomas HE, Kay TW, Birnberg NC, Steinberg GR, Kemp BE and Oakhill JS (2015). Inhibition of AMP-Activated Protein Kinase at the Allosteric Drug-Binding Site Promotes Islet Insulin Release. Cell Chemical Biology. 22, 705-711.
- Scott JW, Ling NXY, Issa SM, Dite TA, O'Brien MT, Chen ZP, Galic S, Langendorf CG, Steinberg GR, Kemp BE and Oakhill JS (2014). Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Cell Chemical Biology. 21, 619-627.
- Green MF, Scott JW, Steel R, Oakhill JS, Kemp BE and Means AR (2011). Ca2+-calmodulin-dependent protein kinase kinase-b is regulated by multi-site phosphorylation. Journal of Biological Chemistry. 286, 28066-28079.
- Scott JW, van Denderen BJW, Jorgensen SB, Honeyman JE, Steinberg GR, Iseli TJ, Oakhill JS, Koay A, Gooley PR, Stapleton D and Kemp BE (2008). Thienopyridone drugs are selective activators of AMP-activated protein kinase b1-containing complexes. Cell Chemical Biology. 15, 1220-1230.
- Scott JW, Ross FA, Liu JKD and Hardie DG (2007). Regulation of AMP-activated protein kinase by a pseudosubstrate sequence on the g subunit. EMBO Journal. 27, 806-815.
- Scott JW, Hawley SA, Green KA, Anis M, Stewart G, Scullion GA, Norman DG and Hardie DG (2004). CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. Journal of Clinical Investigation. 113, 274-284.
- Scott JW, Norman DG, Hawley SA, Kontogiannis L and Hardie DG (2002). Protein kinase substrate recognition using the recombinant catalytic subunit of AMP-activated protein kinase and a model substrate. Journal of Molecular Biology. 317, 309-323.
Appointments and affiliations
- Team Leader, Neurometabolism Group, St Vincent’s Institute of Medical Research
- Senior Honorary Research Fellowship, The Florey Institute of Neuroscience and Mental Health
- Scientific Advisory Board, Siragen Pharmaceuticals
International journal review panel
- Editorial Board Member, Scientific Reports
Grant agency review panels
- NHMRC Ideas Grant Review Panel