Grant: Project Grant

Stem cells provide the source material for development, tissue maintenance and wound repair. They are able to provide these functions because of their unique ability to both self-renew and differentiate. Self-renewal, or the ability to make new stem cells, ensures that a stem cell population is maintained. Differentiation is the process by which these cells form the desired tissue. A balance must be maintained between self-renewal and differentiation in order for stem cells to function properly. If there is too much self-renewal, a tumour may form instead of the desired tissue. If there is too much differentiation, the stem cell population will become depleted, preventing the desired tissue from being formed in the future. We study the genetic and molecular mechanisms that control the balance between self-renewal and differentiation. As a model, we use the germ line of the small nematode worm, C. elegans. This model is one of the best-understood stem cell systems due to the vast array of investigative tools that are available. We have identified a number of genes that, when mutated, cause the balance between self-renewal and differentiation to become compromised. By studying how these genes function, we will determine the molecular mechanisms involved in regulating stem cell behaviour. Importantly, each of the genes we have identified have similar genes in humans, which are also thought to be involved in regulating stem cell proliferation; therefore, our analysis will be directly applicable to understanding human stem cell behaviour. We are also taking the next step in understanding stem cell behaviour by identifying the proteins that are enriched in stem cells. Through this exquisitely sensitive stem cell system, we will determine the proteins that provide stem cells with their unique characteristics. Understanding how specific factors regulate stem cell behaviour will bring us closer to realizing their full therapeutic potential.