Roles of the sumoylation machinery in regulating pluripoptent stem cells

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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.