The cellular fuel gauge: Novel mechanisms of metabolic control

Summary All living organisms have a critical need to couple energy and nutrient supply with growth. A major sensor of the nutrient status of a cell’s environment is the evolutionarily conserved AMP-activated protein kinase (AMPK). AMPK acts as the cell’s fuel gauge by directly sensing energy state (AMP, ADP and ATP), and orchestrating multiple branches of metabolism by phosphorylating and regulating key rate-limiting enzymes in these pathways. Our research goal is to bridge this knowledge gap by hunting for regulatory AMPK kinases and metabolite ligands.

Project Details

All living organisms have a critical need to couple energy and nutrient supply with growth. A major sensor of the nutrient status of a cell’s environment is the evolutionarily conserved AMP-activated protein kinase (AMPK). AMPK acts as the cell’s fuel gauge by directly sensing energy state (AMP, ADP and ATP), and orchestrating multiple branches of metabolism by phosphorylating and regulating key rate-limiting enzymes in these pathways.

AMPK is a heterotrimer complex composed of catalytic a (isoforms a1/2) and regulatory b (b1/2) and g (g1/2/3) subunits. While the majority of research effort has targeted downstream effects of AMPK signalling, relatively little is known about how AMPK itself is regulated. For example, ~150 phosphosites have been identified on AMPK, yet only a handful of upstream kinases have been characterised. Our research goal is to bridge this knowledge gap by hunting for regulatory AMPK kinases and metabolite ligands.

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