Roles of the sumoylation machinery in regulating pluripoptent stem cells

自从詹姆斯·E·史密斯博士的开创性发现以来，Till和Ernest A. McCulloch（两位著名的加拿大科学家）在20世纪60年代初，干细胞已经成为生物学中重要的调节者，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来治疗不同的疾病，因此具有巨大的希望和潜力来彻底改变医学，这不仅将提高世界各地每个人的生活质量，而且还将提供新的方法来降低医疗保健成本，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，需要进行更多的基础研究来实现这一巨大潜力。等待进一步研究的一个基本问题是翻译后修饰（即，蛋白质在制造后的修饰）调节干细胞。翻译后修饰的一个突出类型是添加一种称为SUMO的小蛋白，但很少有人知道它如何在干细胞中发挥作用。我们已开始这方面的研究，并在此提议继续这方面的努力。我们的工作假设是，类小泛素化在胚胎干细胞和诱导多能细胞的自我更新中起着至关重要的作用，以及在它们分化成各种体细胞谱系。考虑到我自己的专业知识和研究兴趣的背景下，在其他实验室，我们建议在这里确定的作用，sumoylation机制在这些多能干细胞，通过追求三个不同的，但互补的研究路线。该项目代表了关于sumoylation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的作用知之甚少的知识空白。该项目将阐明如何改善当前的细胞治疗策略，是我们现有研究计划的逻辑延伸（也是补充），旨在了解不同类型的翻译后修饰如何在不同的细胞过程中调节蛋白质功能。该项目将为两名博士生成为高素质的年轻科学家提供极好的机会。

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.