PhD Opportunity – Regulation of AMP-activated protein kinase by steroids

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Project background: AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade activated by low energy levels [1]. AMPK phosphorylates targets leading to suppression of ATP-consuming pathways and stimulation of ATP producing pathways, such that the AMP:ATP ratio returns to normal [1]. Reduced levels of nutrients can therefore activate AMPK if they cause ATP levels to fall. Similarly, overnutrition may suppress AMPK activity. As a consequence, activation of AMPK has been proposed as a potential therapy for metabolic disorders including obesity and type 2 diabetes. Recent studies have indicated that the steroid glucocorticoid hormones, that regulate metabolism and are anti-inflammatory, can activate AMPK in macrophages [2]. Furthermore, the glucocorticoid dexamethasone has been reported to activate AMPK in muscle, liver and hypothalamus [3,4], yet inhibit AMPK in adipocytes [3]. AMPK also has anti-inflammatory actions [5].

This project will examine whether glucocorticoids and other steroid hormones regulate AMPK and whether AMPK conversely influences steroid signalling. Furthermore, the functional consequences of any such regulation will be investigated.

Techniques: The project will provide excellent training in a range of techniques associated with molecular biology, cell biology and biochemistry. These include but are not limited to mammalian cell culture, gel electrophoresis and immunoblotting, fluorescence microscopy, nutrient flux and signalling assays.

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