Simon Cook

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Protein kinase signalling pathways and life or death decisions

During development cells are faced with a variety of important ‘decisions’ such as whether to progress through the cell cycle and divide or to arrest and differentiate. Even the decision to survive or to die by apoptosis is of fundamental importance to normal development. These decisions are dictated by developmental cues such as growth factors that exert their effects within the cell by activating a variety of signal transduction pathways.

These signalling pathways include the mitogen-activated protein kinases (MAPKs), the dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) and the mammalian target of rapamycin (mTOR) protein kinase.  They play central roles in coordinating cell division and death in response to growth factors, stresses and nutritional cues.  These functions and regulation are substantially conserved in yeast, worms, flies and man.

These signalling pathways are of inherent biological interest if we are to understand normal cellular and organismal homeostasis.  They are regulated by growth and differentiation factors to coordinate development and repair.  In addition, they are activated in response to many stressful stimuli and play a role in coordinating adaptive responses to such insults throughout life.  These pathways are also important because they are frequently de-regulated in a variety of diseases including cancer, autoimmunity and neurodegeneration, where they represent potential new drug targets.

We are seeking to understand the role of these pathways in cell cycle control, metabolic control and cell survival/apoptosis.  In addition, through collaborations with charities and pharmaceutical companies (AstraZeneca & Senexis) we are also studying their role in human tumour cells and in neuro-inflammatory signalling.  We employ a variety of strategies including: use of conditional protein kinases to rapidly activate defined protein kinase pathways; selective inhibitors of these pathways, some of which are novel proprietary drugs in clinical trials; proteomics, to identify new kinase substrates and genomics to identify new kinase pathway gene targets.

For more information about our research and who we are see the Cook Group web pages