Transcriptional regulation and metabolism.

Understanding organisms from a systems perspective is essential for predicting cellular behaviour as well as designing gene-metabolic circuits for novel functions. The structure, dynamics and interactions of cellular networks are all vital components of systems biology. To facilitate investigation of these aspects, we have developed an integrative technique called network component analysis, which utilizes mRNA expression and transcriptional network connectivity to determine network component dynamics, functions and interactions. This approach has been applied to elucidate transcription factor dynamics in Saccharomyces cerevisiae cell-cycle regulation, detect cross-talks in Escherichia coli two-component signalling pathways, and characterize E. coli carbon source transition. An ultimate test of system-wide understanding is the ability to design and construct novel gene-metabolic circuits. To this end, artificial feedback regulation, cell-cell communication and oscillatory circuits have been constructed, which demonstrate the design principles of gene-metabolic regulation in the cell.