CSRIO Molecular & Health Technologies
Acetyl CoA carboxylase- A target for control of obesity and diabetes
Supervisor: Dr Lance Macaulay
Location: CSIRO Molecular and Health Technologies
Contact: Dr Lance Macaulay T: +61 3 9662-7335 Email: Lance.Macaulay@csiro.au
Central adiposity is associated with insulin resistance and is predictive of diabetes. Fat synthesis and breakdown is controlled in part by different forms of acetyl CoA carboxylase, ACC1 (essential for life) and ACC2 respectively. Animals in which ACC2 is deleted/inhibited are leaner and able to tolerate high fat diets, confirming this protein as a therapeutic target. This project seeks :to characterise the human carboxyl transferase (hCT) domain of ACC2. This will be accomplished by cloning several CT domain proteins, the development of assays to measure the activity of this domain including characterisation of metabolite regulators amenable for screening ACC2 inhibitors, as well as the initiation of protein crystallisation trials. The project will involve molecular biology in the cloning of various CT domain constructs of ACC2 for expression studies, cell based assays and recombinant protein production for in vitro investigation of these interactions. The project will therefore provide a rounded experience in protein chemistry and cell and molecular biology.
Calmodulin dependent kinase kinase - A target for control of obesity and diabetes
Supervisor: Dr Lance Macaulay
Location: CSIRO Molecular and Health Technologies
Contact: Dr Lance Macaulay T: +61 3 9662-7335 Email: Lance.Macaulay@csiro.au
Recent studies have identified calmodulin dependent kinase kinase (CamKK) as a kinase that regulates AMPK activity, the key enzyme controlling energy balance of the cell. We have expressed CamKK and now wish to explore its potential in controlling obesity related conditions including diabetes. The student project has been developed to express various domains of CamKK and screen for inhibitors of the enzyme using inhibitor libraries developed in our Division as part of CSIROs Preventative Health Flagship program. The project will involve cloning of protein domains, recombinant protein production, crystallography for structure determination and development of protein and intact cell screening assays for inhibitor analysis. The project will therefore provide a rounded experience in protein chemistry, cell and molecular biology.
These projects form part of a program run through CSIRO and SVIMR with Lance Macaulay and Bruce Kemp aimed at understanding the molecular links between diet and exercise that are important for maintaining health and protecting the body from age onset diseases that include obesity, diabetes, hypertension, cardiovascular disease and cancer.