Programming cellular responses through engineering exclusive cytokine: receptor pairs

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The ability to precisely control cellular signaling events is paramount to survival of every living organism. Not surprisingly, the ability to program these events to elicit desired biological responses has the potential to transform how we study fundamental biological processes and offers tantalizing opportunities for the development of biotechnological applications for novel cell based therapies. In support of these goals, we propose to strategically engineer variant forms of cytokine:receptor complexes that, through exclusive pairing, confer precise control of cellular signaling events. The general concept is to introduce complementary mutations into a cytokine and its receptor to abolish binding to their native partners while conferring exclusive binding to one another. To achieve these aims, we have assembled a team of leading Canadian scientists from academia and industry with expertise in in silico based molecular design, protein engineering and cellular biology. Using these approaches we will develop a robust process whereby sophisticated, highly programmable sets of complementary cytokine:receptor pairs will afford precise control of complex cell signaling events.