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Structure/function of AMP/drug synergy

Structure/function of AMP/drug synergy

PhD/Honours project

We have uncovered a novel activation mechanism for the master metabolic regulator AMP-activated protein kinase (AMPK), an important drug target for a range of diseases. Unphosphorylated AMPK can be synergistically activated by AMP and the drug A-769662. For 30 years AMPK was widely thought to be inactive until phosphorylated by upstream kinases. This breakthrough is pertinent to circumstances where there is genetic loss of upstream kinase (LKB1) in a variety of cancer models. We have since demonstrated that the drug C2 can replace AMP as a synergy partner, providing a roadmap for combinatorial therapies aimed at AMPK activation. Projects are available aimed at characterizing this novel regulatory mechanism and evaluating its physiological significance. Training will be provided in a wide range of techniques including protein biochemistry, protein crystallography, mass spectrometry, cell culture, metabolic profiling of genetic mouse models.

Training will be provided in a number of techniques including molecular biology, protein biochemistry, protein expression and purification, crystallography, mass spectrometry, primary cell culture, genetic mouse models.

Supervised by:

  • Dr Jonathan Oakhill
  • Dr John W. Scott
  • Prof Bruce E. Kemp
  • Dr Christopher Langendorf
  • Disease Focus:

  • Type 2 diabetes
  • Research Unit:

  • Metabolic signalling