Grant: Doctoral Research Award: Canada Graduate Scholarships

Due to their ability to continuously divide and produce all the cell types in our bodies, pluripotent stem cells (PSCs) represent a powerful tool for understanding development and for making therapeutic cells. Research has shown that these cells are constantly competing with one another, killing their unhealthy neighbours. This process, cell competition (CC), has been shown both with cells in a dish and in embryonic development across several species. While our knowledge of what kinds of unhealthy cells are eliminated has been growing, the essence of how this is sensed and communicated to their neighbours remains unknown. Recent work aimed at understanding CC in the early embryo has focused on comparing cells by their mRNA using available methods. However, work in other species has shown that one defining feature of unhealthy cells is an inability to produce as much protein from mRNA. This means that key differences between competing cells may have been missed. Using cutting-edge techniques for examining differences at the protein level, I want to understand and control these precious cells while they compete with one another. I will grow established winner and loser cells in isolation and in a mixed culture. I will measure the abundance of all proteins inside the cells of each of these conditions, looking for those that become more or less abundant during competition. Using a cutting-edge method and a new synthetic biology tool together, I will measure in individual cells the rate of protein production of from individual mRNAs. Using this, I can find mRNAs that are translated differently during competition, suggesting they have a role in driving this process. Finally, by finding these proteins, I can by increase or decrease their abundance directly, either driving or preventing CC. By controlling CC in this way, we can gain further insight into the role of competition during development and can better control the production of next generation cell-based therapies.