Reverse engineering the bacterial cell’s control system Harley McAdams, Stanford University School of Medicine

The bacterial cell cycle control system is hierarchically organized with a core engine created by a cyclical genetic circuit. This engine activates modular genetic subsystems in the correct order to replicate the chromosome, construct polar organelles, and divide the cell. Environmental and internal status sensors feed into the core engine and the metabolic subsystem to adjust protein production and the cell’s rate of growth as necessary. Computational tools are invaluable adjuncts to biochemical and genetic experiments necessary to identify the novel molecular mechanisms and pathways in the control system. Recent computational advances include (1) a new method to identify transcription start sites, DNA binding motifs, and regulons, (2) an new algorithm that identifies additional proteins interacting with known interacting proteins with much higher accuracy than other approaches, and (3) a new simulation model of the cell cycle control system using engineering tools. Recent discoveries of widespread epigenetic regulatory mechanisms, regulatory RNAs, and cell topology-dependent regulatory switching mechanisms challenge conventional views of bacterial cell regulation.