Reference number : GC-2017-Q1-02045, amendment number : , agreement type : G, recipient legal name : Autexier, Chantal (McGill University)|Autexier, Chantal (Université McGill), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : 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., program purpose french : 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., agreement title english : Regulation of chromosome end maintenance by recombination, agreement title french : Regulation of chromosome end maintenance by recombination, agreement number : RGPIN, agreement value : 140000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada