How internal interactions between the processive phases of eukaryotic protein synthesis control flux through the overall system

真核蛋白质合成过程阶段之间的内部相互作用如何控制整个系统的通量

• 批准号: BB/F01838X/2
• 负责人: John McCarthy
• 金额: $ 14.41万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF01838X%2F2
• 关键词: How; internal; interactions; between; processive

The information contained in the genes of living cells has to be converted into cellular components that form structures and enable biochemical reactions to take place. This process is called gene expression and it is vital to all life. Gene expression comprises two main steps, called transcription and translation. In transcription, the information in the DNA sequences of the genes is converted into equivalent sequences in so-called messenger RNA (mRNA) molecules. In translation, the mRNA molecules are 'read' by a large molecular structure called the ribosome, which uses the information to dictate the synthesis of proteins. One of the major goals of science today is to place our knowledge of biology on a quantitative footing. This is the only way in which we will achieve a full understanding of how living systems work. In this project, we will apply this principle to the process of translation, determining numerical answers to questions about how the components of the system interact with each other and also control how fast protein synthesis takes place. This will lead to the development of new understanding of how the component steps of protein synthesis interact with each other. As a result, we will be able to model better the behaviour of protein synthesis in vivo, thus opening up new opportunities to make the study of this fascinating process more rigorous and exact. Moreover, this type of systems analysis will help us determine how best to influence the rate of protein synthesis using drugs such as antibiotics. Since the targeting of such drugs to protein synthesis in bacterial and fungal organisms is potentially of great significance to human health, this work may accordingly contribute to the development of novel therapeutic strategies in the healthcare sector.

活细胞基因中包含的信息必须转化为形成结构并使生化反应能够发生的细胞成分。这个过程被称为基因表达，它对所有生命都至关重要。基因表达包括两个主要步骤，称为转录和翻译。在转录过程中，基因的DNA序列中的信息被转换成所谓信使RNA（mRNA）分子中的等同序列。在翻译过程中，mRNA分子被称为核糖体的大分子结构“读取”，核糖体使用信息来决定蛋白质的合成。当今科学的主要目标之一是将我们的生物学知识建立在定量的基础上。只有这样，我们才能充分理解生命系统是如何工作的。在这个项目中，我们将把这个原理应用到翻译过程中，确定关于系统组件如何相互作用的问题的数值答案，并控制蛋白质合成的速度。这将导致对蛋白质合成的组成步骤如何相互作用的新理解的发展。因此，我们将能够更好地模拟体内蛋白质合成的行为，从而开辟新的机会，使这一迷人的过程的研究更加严格和准确。此外，这种类型的系统分析将帮助我们确定如何使用抗生素等药物最好地影响蛋白质合成速率。由于这些药物靶向细菌和真菌生物体中的蛋白质合成对人类健康具有潜在的重要意义，因此这项工作可能有助于医疗保健领域新治疗策略的开发。

项目成果

A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes.

基于其所有酶的一致动力学表征的酵母糖酵解模型。

• DOI: 10.1016/j.febslet.2013.06.043
• 发表时间: 2013-09-02
• 期刊: FEBS letters
• 影响因子: 3.5
• 作者: Smallbone K;Messiha HL;Carroll KM;Winder CL;Malys N;Dunn WB;Murabito E;Swainston N;Dada JO;Khan F;Pir P;Simeonidis E;Spasić I;Wishart J;Weichart D;Hayes NW;Jameson D;Broomhead DS;Oliver SG;Gaskell SJ;McCarthy JE;Paton NW;Westerhoff HV;Kell DB;Mendes P
• 通讯作者: Mendes P

Rate control in yeast protein synthesis at the population and single-cell levels.

在群体和单细胞水平上控制酵母蛋白质合成的速率。

• DOI: 10.1042/bst20150169
• 发表时间: 2015
• 期刊: Biochemical Society transactions
• 影响因子: 3.9
• 作者: Dacheux E