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Analysis and Design of Genetic and Metabolic Control Systems of Bacterial Cells

Molecular biology permits custom programming of cells to carry out specific tasks, such as synthesis of specific biomolecules or modification of molecules in the extracellular environment. Further examples include formation of multicellular structures or sending chemical or optical signals in response to detection of specific molecules. The bacterium Escherichia coli, for which there exists a staggering array of genetic engineering methods and genomic data, is well suited for such tasks. Efforts at bioengineering of E. coli depend on understanding unresolved basic questions of the mechanisms underlying control of gene expression (i.e., modulation of which genes are expressed at any given time, largely through DNA-protein interactions on the chromosome) and metabolic processes (i.e., the biochemical reaction pathways through which the basic molecules of a cell are processed). The overall objective of this project is to biologically engineer bacterial cells, and design them to perform specific tasks and to produce specific materials. Two complementary projects focus on understanding mechanistic aspects of gene expression and metabolic processes in E. coli. Key strengths of the project are the complementary abilities of the collaborating groups in the areas of theoretical study of metabolic and genetic networks of E. coli, study of information in genetic sequences, theoretical and experimental study of protein-DNA interactions at the single-molecule level, experimental study of chromosome structure and function, and theoretical and experimental study of soft materials including supramolecular assemblies of biomolecules.