Stress genes and the molecular basis of resistance

了解生物体如何对各种化学物质和环境的侵害产生抗性，可能是预测癌症化疗结果或规划全球温度波动影响等各种科学目标的核心。例如，一项对果蝇对甲氨蝶呤耐药性的分子遗传学研究似乎有望成为理解人类和其他哺乳动物胚胎发育异常的模型，这些异常是母亲服用甲氨蝶呤后造成的。利用基因工程技术和“基因芯片”（包含在特定生物体中发现的工作DNA序列的幻灯片），我们将能够识别受药物治疗影响的基因。在另一个例子中，我们知道冬季条件诱导或增强了一些应激蛋白的表达，包括干燥、寒冷、渗透胁迫和抗冻蛋白。我们对那些昆虫和植物中的冷应激基因和蛋白质感兴趣，我们有一些经验，包括加拿大北方森林的主要害虫（云杉budworm），储存谷物的害虫（粉虫），草坪草和果蝇。同时，我们将应用新的选择技术来识别那些含有编码冷适应分子的基因的微生物。本提案中描述的实验可以帮助建立有效和对环境负责的害虫控制，对有益物种的工程抗性有用，或者最终甚至为工业提供有用的“绿色”抑制剂。对基础科学来说，这些“抗寒和抗冻基因”的研究为更好地理解基因调控、基因转移和应激适应的分子进化提供了希望。抗寒和抗冻基因对于抵御各种压力至关重要。

Understanding how organisms become resistant to a variety of chemical and environmental insults may be central for scientific goals as diverse as predicting the outcome of cancer chemotherapy or planning the impact of global temperature fluctuations. For example, a study of the molecular genetics of resistance to methotrexate in fruit flies appears to hold promise as a model for understanding the developmental abnormalities seen in human and other mammalian embryos that result when mothers are prescribed this drug. Using the techniques of genetic engineering as well as "gene chips" (slides that contain the working DNA sequences found in a particular organism), we will be able to identify the genes that are affected by drug treatments. In another example, we know that winter conditions induce or enhance the expression of a number of stress proteins including those for desiccation, cold, osmotic stress and antifreeze proteins. We are interested in cold stress genes and proteins in those insects and plants for which we have some experience,including Canada's premier pest of the boreal forest (spruce budworm), a stored grain pest (Tenebrio mealworms), a turf grass and the fruit fly.  As well, we will apply novel selection techniques to identify those microorganisms that contain genes that encode molecules for cold adaptation. The experiments described in this proposal could help establish effective and environmentally responsible pest control, be useful for engineering resistance to beneficial species, or eventually even provide useful "green" inhibitors to industry. To basic  science,these studies of "cold and freeze resistance genes", which are crucial for survival against a variety of stresses, offer the promise of greater understanding of gene regulation, gene transfer and the molecular evolution of stress adaptation.