Biochemical and genetic characterization of ribosome biogenesis and functional diversity

核糖体是复杂的分子机器，在将遗传密码翻译成蛋白质方面发挥着核心作用。核糖体被认为是现代细胞的基础和生命的本质。事实上，人们认为核糖体是具有统一功能的标准蛋白质工厂。在这个项目中，我们挑战这一概念，并提出存在一个密码，将核糖体的产生和功能与细胞的需要和生长条件的变化联系起来。在面包酵母中，核糖体由核糖核酸（RNA）和由大量复制基因产生的几种蛋白质组成。重复的核糖体蛋白基因在序列上非常相似，并且被认为具有冗余功能。令人惊讶的是，我们发现这些看似功能相同的重复基因并不是平等表达的，并且parolog缺失导致基因拷贝特异性表型效应。这意味着重复的基因表现出拷贝特异性功能。 在这个项目中，我们将系统地研究调节重复核糖体蛋白基因表达的机制，并测量它们对细胞功能和应激反应的影响。我们将确定重复的基因如何沟通，以建立一个特定的核糖体蛋白质的比例，并监测改变不同的核糖体成分的合成和组装上建立的表达模式的影响。对细胞功能的影响将使用一组预定的表型测试来测量，使我们能够确定需要产生专门核糖体的特定应力和生长条件。该项目的成果不仅将提供有关细胞功能的基本信息，还将帮助我们了解细胞如何对其环境做出反应，并为我们提供一种新的方法来确定如何实现功能多样性。

Ribosomes are intricate molecular machines playing a central role in translating the genetic code into proteins. Ribosomes are considered the basis of modern cells and the essence of life. Indeed, it was believed that ribosomes are standard protein factories with uniform functions. In this project, we challenge this notion and propose the existence of a code linking ribosome production and function to cellular needs and changes in growth conditions. In baker's yeast, ribosomes are made of ribonucleic acid (RNA) and several proteins generated from a large set of duplicated genes. The duplicated ribosomal protein genes are very similar in sequence and were believed to have redundant function. Surprisingly, we discovered that these duplicated genes with seemingly identical functions are not expressed equally, and the parolog deletions lead to gene copy specific phenotypic effect. This means that duplicated genes exhibits copy specific function. In this project, we will systematically examine the mechanism regulating the expression of duplicated ribosomal protein genes and measure their impact on cell function and response to stress. We will determine how the duplicated genes communicate to establish a specific ribosomal protein ratio and monitor the impact of altering the established expression pattern on the synthesis and assembly of the different ribosome components. The impact on cell function will be measured using a pre-determined set of phenotypic tests allowing us to identify specific stresses and growth conditions requiring the production of specialized ribosomes. The outcome of this project will not only provide fundamental information about how the cell function but will also help us understand how cells respond to their environment and give us a new approach to determine how functional diversity is achieved.