Molecular control of non-histone protein acetylation in budding yeast

芽殖酵母非组蛋白乙酰化的分子控制

• 批准号: RGPIN-2021-03887
• 负责人: Downey, Michael
• 金额: $ 5.03万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742772
• 关键词: Molecular; control; non; histone; protein

Managing Cellular Factories: If we think of our cells that make up our bodies as small factories, the proteins in the cell are the workers. Each of us has thousands of these worker proteins in each cell. As you might imagine, things get pretty crowded and organization is needed to make sure things run smoothly. To this end, some specialized proteins called enzymes act as the managers of the cell. They communicate instructions to worker proteins using chemical signals. These instructions determine what jobs get done. My lab works on two types of enzyme "managers", called KATs and KDACs. These regulate a set of instructions in the cell called acetylation. Acetylation is a chemical modification that is placed onto proteins by KATs and removed by KDACs. We have uncovered evidence that acetylation is a common set of instructions handed out to many proteins around the cell. The long-term goal of this research program is to advance knowledge by determining how KAT and KDAC enzymes know which proteins to contact with acetylation `instructions'. In our short term aims, we will investigate a novel idea put forth by a former MSc student, that specific KAT and KDAC enzymes work together to regulate the acetylation of the same proteins. We can think of this as managers from different departments collaborating on the same project. We will investigate this hypothesis using a collection of advanced techniques including an instrument called a mass spectrometer that allows us to identify acetylations on individual proteins. The program, which is based on work completed with our previous NSERC funding, will use the simple baker's yeast S. cerevisiae, which serves as an excellent model of a eukaryotic (advanced) cell. But, yeast is easily amendable to work in the lab, which will speed completion of the project aims. The work will be carried out by my MSc student, a PhD-trained post-doctoral fellow, and approximately ten undergraduate students. The students will receive expert training in technologies that are in demand in industry and academia. They will also receive training in communications, and equity, diversity and inclusion (EDI). Finally, they will conduct outreach within the community. The output of the work is new knowledge about fundamental processes that occur in different types of cells. Since the work is in yeast, there are also applications in the biotechnology industry including the use of yeast in wine making and the production of alternative fuels. As such our program is of tremendous value to Canada.

管理细胞工厂：如果我们把构成我们身体的细胞想象成小工厂，那么细胞中的蛋白质就是工人。我们每个人的每个细胞中都有成千上万个这样的工作蛋白。正如你所想象的，事情变得非常拥挤，需要组织来确保事情顺利进行。为此，一些称为酶的特殊蛋白质充当细胞的管理者。它们利用化学信号向工作蛋白传达指令。这些指令决定了要做什么工作。我的实验室研究两种类型的酶“管理器”，称为KAT和KDAC。它们调节细胞中一组称为乙酰化的指令。乙酰化是一种化学修饰，通过KAT置于蛋白质上并通过KDAC去除。我们已经发现了乙酰化是细胞周围许多蛋白质的一组常见指令的证据。 这项研究计划的长期目标是通过确定KAT和KDAC酶如何知道哪些蛋白质与乙酰化“反应”接触来推进知识。在我们的短期目标中，我们将研究一位前硕士生提出的新想法，即特定的KAT和KDAC酶一起调节相同蛋白质的乙酰化。我们可以把这看作是来自不同部门的经理在同一个项目上的合作。我们将使用一系列先进技术来研究这一假设，包括一种称为质谱仪的仪器，它使我们能够识别单个蛋白质上的乙酰化。该计划，这是基于我们以前的NSERC资金完成的工作，将使用简单的面包酵母S。酿酒酵母，其充当真核（高级）细胞的优良模型。但是，酵母很容易在实验室中工作，这将加快项目目标的完成。这项工作将由我的硕士学生，一个博士培养的博士后研究员和大约10名本科生进行。学生将接受行业和学术界需求的技术专家培训。他们还将接受通信、公平、多样性和包容方面的培训。最后，他们将在社区内开展外联活动。这项工作的成果是关于不同类型细胞中发生的基本过程的新知识。由于这项工作是在酵母中进行的，因此在生物技术工业中也有应用，包括在酿酒和生产替代燃料中使用酵母。因此，我们的计划对加拿大具有巨大的价值。