Measuring the effect of environmental stress on checkpoint, genome instability and survival

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Cells have a remarkable ability to survive toxic stress. Different kinds of stress –harmful drugs, UV light, heavy metals like mercury– have different outcomes. My work examines DNA damaging drugs. DNA determines how we grow, change, and how our children develop. When DNA is damaged by a drug, the cell activates a pathway that STOPS its growth. By STOPPING growth, a cell can assess damage, repair it and then resume healthy division. These STOP pathways are called “checkpoints.” I am interested in how checkpoints work and why they fail. A faulty checkpoint causes massive problems including DNA rearrangements and death. Many cancers are a direct result of checkpoint failures. Our work uses yeast. It is fast growing, inexpensive, and shares all the critical components of mammalian checkpoint pathways. Analyzing how yeast survives DNA damage helps us understand how the same kind of damage affects all life. Cells in the real world face changes in temperature, nutrition, pH, etc. These environmental stresses activate specific stress pathways to promote cellular survival. Lab conditions allow us to examine checkpoints without stresses, giving an initial picture of how the checkpoint works. We can then introduce stresses alone, or in combination, to measure their effect. Our core research questions are: Does a change in environmental stress have an effect on DNA damage checkpoint? Do cells survive? I previously found that environmental stress changes a cell’s ability to survive DNA damage. This NSERC research project will determine how environmental changes affect cell survival and DNA mutation. We ask whether the mutated cells are different from the original, and what this means to the whole animal/plant. We expect to find new checkpoint factors that improve health after DNA damage. A team of junior scientists and university students at Ryerson University will perform these experiments and accomplish our goals. These highly trained Canadians graduate with the skills and knowledge to tackle important questions in research and industry. Our collaborators at Ryerson, and internationally, will include ecologists, biologists and computer scientists. We will examine how entire organisms are affected in ageing and disease. Our preliminary evidence shows that cells change DNA damage checkpoints under stress. We do not know how it happens or the consequences. Our work testing multiple variables in yeast to predict consequences in other organisms is a powerful tool to understand how cells behave in the real world. We look to encourage discussion between academic, government, and private sectors. Canada’s leadership role in ecology, preservation and agriculture ensures that our work will impact research on changing environmental times.