Grant: Operating Grant

Stem cells provide the source material for the generation of tissues in the developing animal, as well as for the turnover of tissues in the adult. They are able to serve these functions due to their unique ability to yield two general types of cells when they divide. One type of cell enters a path to differentiation, thereby forming the needed tissue. The other type of cell is essentially identical to the parental stem cell, with the continued ability to produce two types of cells. A dividing stem cell is able to produce both types of daughter cells. A balance must be maintained between cells that take on the character of the parental cell (self-renew) and those cells that differentiate into the desired tissue. If too many of the cells differentiate, the pool of self-renewing cells is depleted, which prevents tissues from being made in the future. Conversely, if too many cells self-renew, a tumour of proliferating cells is formed at the expense of the differentiated tissue. In my lab, we study the genetic and molecular mechanisms that control the balance between self-renewal and differentiation. We are using the germ line of a small nematode worm, C. elegans, as a model to study how stem cell self-renewal is regulated. To build upon our current understanding of how stem cell proliferation is controlled, we are studying the activities of genes that cause a tumour, when mutant. One of these genes, puf-8, encodes a protein that is similar to proteins in humans that are expressed in germline stem cells. Another protein, KIN-10, is similar to a human protein that has been implicated in forming tumours. By studying how the balance between stem cell self-renewal and differentiation is controlled in the C. elegans germ line, we will be able to uncover themes that may be found in other stem cell niches. The full therapeutic potential of stem cells depends upon our understanding how stem cell behavior is regulated.