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

细胞有一种非凡的能力，可以在有毒的压力下生存。不同种类的压力--有害药物、紫外线、汞等重金属--会产生不同的结果。我的工作是检查破坏DNA的药物。DNA决定了我们如何成长、改变，以及我们的孩子如何发展。当DNA被药物破坏时，细胞会激活一条停止其生长的途径。通过停止生长，细胞可以评估损伤，修复它，然后恢复健康的分裂。这些停车通道被称为“检查点”。我对检查站是如何工作的以及它们失败的原因感兴趣。一个错误的检查站会导致大量问题，包括DNA重排和死亡。许多癌症是检查站故障的直接结果。*我们的研究使用了酵母。它生长迅速，价格低廉，并共享哺乳动物检查点途径的所有关键组件。分析酵母如何在DNA损伤中幸存下来，有助于我们了解相同类型的损伤是如何影响所有生命的。*现实世界中的细胞面临温度、营养、pH等方面的变化。这些环境应激激活特定的应激途径，促进细胞存活。实验室条件允许我们在没有压力的情况下检查检查点，从而初步了解检查点是如何工作的。然后，我们可以单独或组合引入压力，以衡量它们的影响。我们的核心研究问题是：环境压力的变化是否会对DNA损伤检查点产生影响？细胞存活吗？我之前发现，环境压力会改变细胞在DNA损伤中存活的能力。NSERC的这一研究项目将确定环境变化如何影响细胞存活和DNA突变。我们问突变的细胞是否与原始细胞不同，这对整个动物/植物意味着什么。我们希望找到新的检查点因素来改善DNA损伤后的健康。*瑞尔森大学的一个由初级科学家和大学生组成的团队将进行这些实验，并实现我们的目标。这些训练有素的加拿大人毕业时拥有解决研究和工业中重要问题的技能和知识。我们在Ryerson和国际上的合作者将包括生态学家、生物学家和计算机科学家。我们将研究整个生物体在衰老和疾病中是如何受到影响的。*我们的初步证据表明，细胞在压力下会改变DNA损伤检查点。我们不知道它是如何发生的，也不知道它的后果。我们的工作是在酵母中测试多个变量以预测其他生物体的后果，这是了解细胞在现实世界中行为的强大工具。我们希望鼓励学术界、政府和私营部门之间的讨论。加拿大在生态、保护和农业方面的领先地位确保了我们的工作将影响对环境时代变化的研究。**

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.**