Programming cellular responses through engineering exclusive cytokine: receptor pairs

精确控制细胞信号事件的能力对每个生物体的生存至关重要。毫不奇怪，对这些事件进行编程以引发所需的生物反应的能力有可能改变我们研究基本生物过程的方式，并为开发基于细胞的新疗法的生物技术应用提供诱人的机会。为了支持这些目标，我们建议战略性地设计细胞因子：受体复合物的变体形式，通过排他性配对，赋予细胞信号事件的精确控制。一般的概念是将互补突变引入细胞因子及其受体，以消除与其原生伴侣的结合，同时赋予彼此的排他性结合。为了实现这些目标，我们组建了一支由来自学术界和工业界的加拿大领先科学家组成的团队，他们在基于硅的分子设计，蛋白质工程和细胞生物学方面具有专业知识。使用这些方法，我们将开发一个强大的过程，即复杂的，高度可编程的互补细胞因子：受体对将提供复杂的细胞信号事件的精确控制。

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.