A Minimal Cell Model to Determine Genomic Structure

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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.