Research units - Protein Chemistry and Metabolism
Protein Chemistry and Metabolism
Our research is concerned with the control of the body’s energy metabolism via an enzyme called AMP-activated protein kinase (AMPK). This enzyme acts as the body’s fuel gauge, determining its energy level and is at the hub of metabolic control in response to diet and exercise.
Research Overview
It is well recognized that diet and sedentary life-styles are major contributors to obesity and cardiovascular disease and regular exercise together with moderate caloric intake are important for maintaining health. For example AMPK controls the synthesis of fats including, triglycerides and cholesterol and is responsible for burning fat in response to exercise.
In the brain AMPK is involved in appetite control. All the body’s functions depend on energy and research on AMPK is likely to greatly increase our understanding of the interrelationships between physiological functions, caloric intake, energy metabolism and exercise. We need to understand the molecular details of how the AMPK is regulated.
In an era of epidemic obesity, diabetes and sedentary lifestyles this research has the potential to provide new therapeutic developments and, even more importantly, new insights for the molecular basis of age onset diseases particularly, obesity, diabetes and cardiovascular disease. We use techniques such as protein chemistry, molecular biology, protein crystallography, mass spectrometry, gene knock out and knock in mouse models to study AMPK.
Research Themes
Control of AMPK signalling by adenylate charge
Development of AMPK isoform specific drugs
Genetic modification of AMPK signaling pathways
Honours and PhD Projects
AMPK regulation of lipid metabolism
Staff
Prof Bruce E. Kemp
Dr John W. Scott
Dr Jonathon Oakhill
Dr Sandra Galic
Dr Zhi-Ping Chen
Dr Rohan Steel
Frosa Katsis
Naomi Ling
Hayley O’Neill
Dr Suzanne Rogers
Lisa Murray-Segal
Publication Highlights
- Oakhill JS, Chen ZP, Scott, JW, Steel R, Castelli LA, Ling N, Macaulay SL and Kemp BE. β-Subunit Myristoylation is the Gatekeeper for Initiating Metabolic Stress Sensing by AMPK. Proc Nat Acad Sci 2010 (in press)
- Steinberg GR, O'Neill HM, Dzamko NL, Galic S, Naim T, Koopman R, Jorgensen SB, Honeyman J, Hewitt K, Chen ZP, Schertzer JD, Scott J, Koentgen F, Lynch GS, Watt MJ, Van denderen BJ, Campbell DJ, Kemp BE. Whole-body deletion of AMPK {beta}2 reduces muscle AMPK and exercise capacity. J Biol Chem. 2010 Sep 20. [Epub ahead of print]
- Dzamko N, van Denderen BJ, Hevener AL, Jorgensen SB, Honeyman J, Galic S, Chen ZP, Watt MJ, Campbell DJ, Steinberg GR, Kemp BE. AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance. J Biol Chem. 2010 Jan 1; 285(1): 115-22.
- Steinberg GR, Kemp BE. AMPK in Health and Disease Physiol Rev. 2009 Jul; 89(3): 1025-78.
- Oakhill JS, Scott JW, Kemp BE. Structure and function of AMP-activated protein kinase. Acta Physiol (Oxf). 2009 May; 196(1): 3-14.
- Scott JW, van Denderen BJ, Jorgensen SB, Honeyman JE, Steinberg GR, Oakhill JS, Iseli TJ, Koay A, Gooley PR, Stapleton D, Kemp BE. Thienopyridone drugs are selective activators of AMP-activated protein kinase beta1-containing complexes. Chem Biol. 2008 Nov 24; 15(11): 1220-30.