Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)

All cells must maintain the integrity of their genetic material (DNA), which is found on chromosomes, in order to live, grow and divide. The ends of chromosomes are called telomeres. Efficient telomere function is necessary for embryonic and adult stem cell function and thus for tissue function throughout life. The essential function of telomeres is highlighted by the fact that defects in genes controlling telomere function leads to a number of diseases, including premature aging syndromes, characterized by proliferative failure of a variety of tissues and death. Telomerase is an enzyme that plays a role in stabilizing telomeres. Telomeres can also be stabilized by a telomerase-independent mechanism known as ALT. Although telomerase appears to be the predominant mechanism of telomere maintenance in stem cells and other highly proliferative normal, immortal, and tumor cells, ALT activity has been reported in early cleavage embryos, during reprogramming in pluripotent stem cells, in normal somatic cells in mammals and in ~fifteen percent of tumor cells. We use cell culture models to identify and understand the process by which stable telomeres prevent cell death, extend the lifespan of a cell, and promote cell survival. My team discovered that one consequence of altering telomere function in a human culture cell model is the increase in telomere maintenance by ALT rather than the promotion of cell death. Our studies aim to identify regulators of the poorly characterized ALT pathway of telomere maintenance. The long term expectations of our studies are that they will inform us about basic telomere biology and provide more global insights into the role of the ALT pathway of telomere maintenance in development, reprogramming in pluripotent stem cells, normal somatic cells and in cell and tissue function. This research is important to Canada as cell and tissue malfunction are the causes of most diseases afflicting Canadians, and the identification of regulators of cell and tissue function can lead to the development of better disease treatments.