Decoding the rules that govern the coordination of the bacterial cell cycle

Abstract Maintaining the integrity of the genome is essential to cell survival. As bacteria grow and divide, they must coordinate numerous molecular machineries for each daughter cell to inherit an intact copy of the chromosome. Miscoordination can be lethal, making these processes potential targets for novel antibiotics. The Mera laboratory uses a systems approach to untangle the complex temporal and spatial coordination that drive the progression of the bacterial cell cycle. The work combines classical genetics, biochemistry, and high- resolution imaging to examine at the molecular level cell cycle coordination. The bacterial model system used is Caulobacter crescentus, which exhibits a dimorphic life cycle. The project proposed has two main goals for the next 5 years: (i) define mechanistic details for how the replication initiator DnaA with the partitioning system ParABS coordinate the initiation of chromosome replication with centromere segregation, and (ii) uncover mechanisms that bacteria use to coordinate chromosomal maintenance to the regulation of cell size and shape over the cell cycle. Furthermore, the proposed work will provide important insights to how cells integrate environmental information (e.g., nutrient availability) into the cell cycle network. The vision of the research program in the Mera lab is to uncover the molecular rules that govern the coordination of the bacterial cell cycle. The understanding of these fundamental rules has the potential to transform our ability to control the growth of bacteria and to drive biomedical innovations.