Integrated systems biology study of the control of protein synthesis capacity and fitness in a eukaryotic microbe.

活细胞基因中包含的信息必须转化为细胞成分，形成结构并使生化反应发生。这个过程被称为基因表达，它对所有已知的生命都至关重要。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DNA序列中的信息在所谓的信使RNA （mRNA）分子中转化为等效序列。在翻译过程中，mRNA分子被一种叫做核糖体的大分子结构“读取”，核糖体利用这些信息来指挥蛋白质的合成。我们想了解活细胞中蛋白质的合成是如何被控制的。为了做到这一点，我们正在对蛋白质合成过程进行一种新型的分析，这种分析告诉我们，制造蛋白质的机器的每个组成部分是如何决定系统工作效率的。我们还将研究这个系统的组成部分是如何在细胞外相互作用的，这样我们就能获得这些分子相互作用方式的详细信息。这些实验产生的定量数据将被输入到计算机中建立的高级模型中。当该模型运行并获得所需的所有信息时，它将成为许多对基因表达感兴趣的研究人员可以使用的非常有用的资源。一个非常有用的特性是能够预测当基因表达过程中出现缺陷时会发生什么——这种缺陷会导致人类疾病。该项目开发和应用的理论和实验技术将对学术界和工业界的广泛研究人员有价值，并将帮助我们了解病变细胞中的基因表达缺陷。

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 known 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. We want to understand how the synthesis of proteins in the living cell is controlled. In order to do this, we are subjecting the protein synthesis process to a new type of analysis that tells us how each component of the machinery that makes proteins contributes to determining how efficiently the system works. We will also be studying how the components of this system interact outside of the cell, so that we obtain detailed information about the ways that these molecules interact with each other. The quantitative data that are generated by these experiments will then be fed into an advanced model set up in a computer. When this model is running and has been fed all of the required information, it will be a very useful resource that can be used by many researchers interested in gene expression. One very useful property will be the ability to predict what happens when there is a defect in the gene expression process - something that can cause disease in humans. The theoretical and experimental technologies developed and applied in this project will be of value to a wide spectrum of researchers in academia and industry, and will help us understand gene expression defects in diseased cells.