Drug development for metabolic diseases

Research Opportunity
PhD, Honours
Number of Honour Places Available
1
Location
St Vincent's Institute of Medical Research
Primary Supervisor Email Number Webpage
A/Prof Jon Oakhill joakhill@svi.edu.au Personal web page
Co-supervisor Email Number Webpage
Prof Bruce Kemp bkemp@svi.edu.au Personal web page
Dr Kevin Ngoei kngoei@svi.edu.au
Dr Chris Langendorf clangendorf@svi.edu.au

Summary AMP-activated protein kinase (AMPK) is a central regulator of cellular energy metabolism that phosphorylates multiple protein targets to adapt cellular metabolism to energy and nutrient availability. AMPK dysregulation is associated with a range of prevalent metabolic diseases (e.g. type 2 diabetes, cancer and cardiovascular disease), thus huge efforts are being made to develop AMPK-targetting drugs. Our aim is to develop 2-specific AMPK activators to trigger AMPK signalling in these tissues without complications associated with off-target effects.

Project Details

AMP-activated protein kinase (AMPK) is a central regulator of cellular energy metabolism that phosphorylates multiple protein targets to adapt cellular metabolism to energy and nutrient availability. AMPK dysregulation is associated with a range of prevalent metabolic diseases (e.g. type 2 diabetes, cancer and cardiovascular disease), thus huge efforts are being made to develop AMPK-targetting drugs.

AMPK is a heterotrimer complex composed of catalytic a (isoforms a1/2) and regulatory b (b1/2) and g (g1/2/3) subunits. A major problem with current pan AMPK-targetting drugs is they activate AMPK throughout the body, causing off-target effects such as cardiac hypertrophy. Intriguingly, AMPK b2-isoform is found almost exclusively in metabolically-active tissues e.g. liver, adipose and skeletal muscle, the latter of which is a validated target tissue for improved glucose control in response to pan-AMPK activators (Merck, Pfizer). Our aim is to develop b2-specific AMPK activators to trigger AMPK signalling in these tissues without complications associated with off-target effects.

As part of our team of 5 postdoctoral scientists, you will receive training from experts in biochemistry, cell biology, x-ray crystallography and mass spectrometry. The team adopts a collaborative approach with studies regularly published in high impact journals.

Keywords: drug development, diabetes, cancer, kinases, protein structure/function


School Research Themes

Cardiometabolic



Research Opportunities

PhD, Honours
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Research Node

St Vincent's Institute of Medical Research

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