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 | Number | Webpage | |
|---|---|---|---|
| A/Prof Jon Oakhill | joakhill@svi.edu.au | Personal web page |
| Co-supervisor | 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
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
Key Contact
For further information about this research, please contact a supervisor.
Research Node
St Vincent's Institute of Medical ResearchMDHS Research library
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