Modeling the temporal dynamics of master regulators and CtrA proteolysis in Caulobacter crescentus cell cycle

Chunrui Xu, Henry Hollis, Michelle Dai, Xiangyu Yao, Layne T. Watson, Yang Cao, Minghan Chen

Abstract: Author summary Timed cellular events in both eukaryotes and prokaryotes, such as chromosome replication, transcription, cell differentiation, cytokinesis, and cell division, are controlled by remarkably complex genetic regulations and protein-protein interactions. In this work, we investigate the cell cycle of Caulobacter crescentus, an alphaproteobacterium undergoing asymmetric cell divisions, to understand mechanisms underlying temporal regulations of complex cellular events. The asymmetric lifestyle makes Caulobacter crescentus easily synchronized and tracked, which is the foundation of molecular data accumulation. Here, we utilize the mathematical modeling together with experimental information to systematically integrate the complex gene-protein and protein-protein interactions in cell cycle progression. Using the mathematical model, we capture core features of cell cycle-dependent methylation, transcription, and proteolysis. In mutant cases, we found the complex and redundant regulatory network ensure the robustness of Caulobacter crescentus system because the change of most molecules does not cause immediate mortality, although they influence the time points of cell differentiation and division. The overall model and individual modules such as simulating transcriptional regulations and protease complexes can be further extended to the study of cell development in other bacterial species.