Roles of the sumoylation machinery in regulating pluripoptent stem cells

自20世纪60年代初两位加拿大著名科学家詹姆斯·E·蒂尔和欧内斯特·A·麦卡洛克博士的开创性发现以来，干细胞已经成为生物学中重要的调节器，并成为再生医学的基石。这些细胞有潜力产生各种类型的细胞用于治疗不同的疾病，因此拥有巨大的希望和潜力来革新医学，这不仅将改善世界各地每个人的生活质量，还将提供新的方法来削减医疗保健成本，这是加拿大和许多国家目前面临的一个严重的预算问题。另一方面，要实现这一巨大潜力，还需要更多的基础研究。一个有待进一步研究的基本问题是，翻译后修饰(即蛋白质制成后的修饰)如何调节干细胞。一种突出的翻译后修饰是添加一种名为相扑的小蛋白，但人们对它如何在干细胞中发挥作用知之甚少。我们已经开始了这方面的研究，并在此建议继续这种努力。我们的工作假设是，苏莫化在胚胎干细胞和诱导的多能细胞的自我更新以及它们分化为各种体细胞谱系的过程中起着关键作用。考虑到我自己的专业知识和其他实验室的研究兴趣，我们在这里建议通过三条不同但互补的研究路线来确定苏莫化机制在这些多能干细胞中的作用。该项目代表了关于苏莫化如何在多能干细胞中发挥作用的基础研究，并填补了目前我们对翻译后修饰在调节多能干细胞中所起作用知之甚少的知识空白。该项目将阐明如何改进目前的细胞治疗策略，是我们现有研究计划的合理延伸(也是对现有研究计划的补充)，目的是了解不同类型的翻译后修饰如何调节不同细胞过程中的蛋白质功能。该项目将为两名博士生提供成为高素质青年科学家的绝佳机会。

Since the pioneering discovery made by Drs James E. Till and Ernest A. McCulloch (two celebrated Canadian scientists) in the early 1960s, stem cells have emerged as important regulators in biology and become cornerstones in regenerative medicine. These cells have the potential to yield various types of cells for treating different diseases and thus holds the great promise and potential to revolutionize medicine, which will not only improve the quality of life for every individual around the world but will also offer novel approaches to cut health care cost, an acute budget issue that Canada and many countries are currently facing. On the other hand, additional fundamental research is needed to realize this great potential. A fundamental question that awaits further investigation is how post-translational modification (i.e., modification of a protein after it is made) regulates stem cells. One prominent type of post-translational modification is addition of a small protein known as SUMO, but very little is known how it may play a role in stem cells. We have initiated research in this regard and propose here to continue such efforts. Our working hypothesis is that sumoylation plays a critical role in self-renewal of embryonic stem and induced pluripotent cells, as well as in their differentiation into various somatic lineages. Considering my own expertise and research interests in the context of those in other laboratories, we propose here to determine the role of the sumoylation machinery in these pluripotent stem cells, by pursuing three different but complementary lines of research. This project represents fundamental research on how sumoylation plays a role in pluripotent stem cells and fills in the current knowledge gap that we know little about role of post-translational modifications plays in regulating pluripotent stem cells. The project will shed light on how to improve current cell therapy strategies and is a logical extension of (and also complements) our existing research program aimed at understanding how different types of post-translational modification regulate protein functions in diverse cellular processes. The project will provide an excellent opportunity for two PhD students to become highly qualified young scientists.