Drug development for metabolic diseases
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.
A/Prof Jonathan Oakhill
Prof Bruce E. Kemp
Type 2 diabetes
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