Methylarginine Dynamics in Cellular Processes

生物体依靠营养物质生长和增殖，但这些资源的可用性有时是有限的。这种情况代表了细胞水平上的压力。单细胞生物酿酒酵母（通常被称为面包酵母）对这种压力的反应进行了研究。研究表明，经历营养剥夺的细胞会发生重大变化，以确保它们在不满的冬季长期生存。在这些条件下，细胞在一个称为自噬的过程中分解并在液泡腔内循环它们的成分，这是延长生物体寿命所必需的。氨基酸精氨酸储存在液泡中，作为许多蛋白质的组成部分之一。我的实验室研究甲基转移酶家族，它将小碳单元连接到蛋白质中的精氨酸末端。这种简单的修饰通过改变分子间的相互作用而对细胞产生深远的影响。我的研究计划的长期目标是确定甲基转移酶活性如何影响广泛的细胞过程，特别是对于NSERC的短期提案，自噬产生的甲基化精氨酸代谢物如何影响细胞存活和寿命。在我们对酵母对营养剥夺的反应的调查中，我们发现细胞外甲基化精氨酸的显著变化依赖于哪个基因被删除。我们计划证明这种氨基酸外排是自噬的产物，并且在压力下阻止酵母的甲基化精氨酸外排会损害长期生存所需的重要过程。我们将在酵母中寻找并表征新的精氨酸甲基转移酶，其基因缺失会影响特定甲基精氨酸物种的外排。为了实现该研究项目的目标，HQP需要广泛的先进的、基于细胞的生化方法，这些方法将为HQP提供分析、沟通和时间管理技能，使其在加拿大自然科学界具有竞争力，并在其知识驱动的经济中具有生产力。我打算用这个NSERC奖培训一个由三名合格HQP组成的多元化团队，他们具有公平和包容性的意识。总之，我们的发现将对我们理解甲基精氨酸代谢如何影响酵母中精氨酸甲基转移酶、自噬和衰老的全球研究人员网络的细胞存活产生深远的影响。

Organisms depend on nutrients to grow and proliferate, but the availability of such resources can be limiting at times. This situation represents a stress on a cellular level. The response to this type of stress is studied in the unicellular organism Saccharomyces cerevisiae, commonly referred to as baker's yeast. Research has emerged that cells experiencing nutrient deprivation undergo significant changes to ensure their long-term survival through the winter of their discontent. Under these conditions, cells break down and recycle their components within a vacuole compartment in a process called autophagy, which is necessary for extending the lifespan of the organism. The amino acid arginine is stored in the vacuole and used as one of many protein building blocks. My laboratory studies a methyltransferase enzyme family that attaches small carbon units to the ends of arginine within proteins. This simple modification exerts profound cellular effects by altering molecular interactions. The long-term objective of my program of research is to determine how methyltransferase activity affects a broad set of cellular processes, and specifically for this NSERC proposal in the short-term, how the methylated arginine metabolites from autophagy affect cell survival and lifespan. In our investigation into the yeast response to nutrient deprivation, we found significant changes on methylated arginine outside of cells that was dependent on which gene was deleted. We plan to show that this amino acid efflux is a product of autophagy, and that preventing methylated arginine efflux from yeast under stress compromises important processes required for long-term survival. We will search for and characterize new arginine methyltransferases in yeast whose gene deletions impact the efflux of specific methylarginine species. The broad range of state-of-the-art, cell-based, and biochemical methods required to achieve the goals of the research program will provide analytical, communication, and time management skills for HQP that will make them competitive within Canada's natural sciences community and productive in its knowledge-driven economy. I intend on training a diverse group of three qualified HQP recruited with an awareness around equity and inclusiveness with this NSERC award. Together, our findings will have a profound effect on our understanding of how methylarginine metabolism affects cell survival in yeast for a global network of researchers studying arginine methyltransferases, autophagy, and aging.