2000 Award Winner

Dr. Dario Alessi
MRC Protein Phosphorylation Unit, University of Dundee, Scotland

The work of Dario Alessi
The work of Dr. Alessi Insulin has long been known as a hormone involved in blood sugar regulation. It is used in the treatment of diabetes, a disease which afflicts five million patients in Germany alone, and 150 million patients worldwide. The mechanism of action of insulin remained an enigma for quite some time now. Dr. Dario Alessi has recently contributed significantly to our understanding of insulin action. He has discovered an enzyme, called protein-dependent-kinase 1 (PDK1), which activates another protein, protein kinase B, through phosphorylation. Phosphorylation and dephosphorylation have long been known as biochemical reactions involved in the regulation of cellular processes. In the particular case of insulin action it turned out to be quite complicated to identify the contribution of phosphorylation reactions. The activation step, catalyzed by PDK1, proceeds in two steps. The first occurs spontaneously, the second requires another protein, called PIF, for PDK1 interacting fragment. Only through this two-step activation procedure can PDK1 be activated to full activity. Dr. Alessi has not only identified these novel insights but has already shown the way of how the activation step through an additional protein can be used to develop drugs which modulate the insulin signaling process. (Abstract from Ernst-Ludwig Winnacker's speech held at the Eppendorf Award Ceremony on November 23, 2000.)

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