A Minimal Cell Model to Determine Genomic Structure

这个项目的目标是建立一个最小细胞的动态数学模型，作为一种工具来确定将基因组的静态线性序列信息与细胞的动态非线性功能联系起来的组织原理。这一模式将分两个阶段发展。首先，将从单个大肠杆菌细胞的现有数学模型创建一个原型最小细胞模型。这个模型基于代表相关化学物种组的参数，并已被证明可以准确地预测细胞的大小、形状、生长速度和组成。在开发的第二阶段，将在原型最小细胞模型中添加有关路径网络的详尽细节，以便单独和明确地描述化学物种和化学反应。在该项目的这一阶段，将增加与染色体复制、核苷酸和脱氧核苷酸合成、运输、转录相关的网络的细节。该项目还将通过实验确定基因的表达与该基因在三维染色体中的位置之间的关系，以便将这一信息包括在基因表达的数学描述中。同步的细胞群体将被用来研究在大肠杆菌分裂周期的不同阶段位置和表达之间的关系。

The objective of this project is to develop a dynamic mathematical model of a minimal cell as a tool to identify the organizing rinciples which relate the static linear sequence information of the genome to the dynamic non-linear functioning of the cell. This model will be developed in two stages. First, a prototype minimal cell model will be created from an existing mathematical model of a single E. coli cell. This model is based on parameters which represent groups of related chemical species and has been shown to accurately predict cell size, shape, growth rate, and composition. In the second stage of development, exhaustive detail on networks of pathways will be added to the prototype minimal cell model so that chemical species and chemical reactions are described individually and explicitly. During this period of the project, details on the networks associated with chromosome replication, ribonucleotide and deoxyribonucleotide synthesis, transport, transcription will be added. This project is to also experimentally determine the relationship between a gene's expression and the position of that gene in the three-dimensional packed chromosome so that this information can be included in mathematical descriptions of gene expression. Synchronized cell populations will be used to study the relationship between position and expression during different phases of the E. coli division cycle.