Quantitative principles of the coupling between DNA replication, cell division, and growth in bacteria

The goal of microbial physiology is to understand the overarching principles of cellular reproduction. In my view, the major challenge in physiological research is to delineate the primary structure of the physiological control of the cell. As such, the goal of my research is to understand how essential cellular processes (e.g., metabolism, DNA replication, or cell division) are coupled in response to environmental changes.

In this talk, I will introduce two principles characterizing the coupling between DNA replication and cell growth, and that between cell division and cell-size control. As for the DNA replication-growth coupling, we hypothesized that the E. coli cell is composed of conceptual “unit cells.” By extensively perturbing the growth physiology in steady-state conditions using genetic and pharmacological methods, we discovered the invariant initiation mass as the basic unit of the cell size. This finding unravels how cells coordinate their biomass and DNA content by imposing a simple and robust control on DNA replication initiation. As for the division-growth coupling, we proposed a hypothesis that bacterial cell division requires the accumulation of division proteins to a fixed threshold number. By combining single-cell microfluidics, programmed genetic modulation, and automated image analysis, we confirmed this hypothesis in evolutionary divergent E. coli and B. subtilis cells. This latter result explains the mechanistic origin of cell-size homeostasis in a wide range of bacterial species that my postdoc lab and others have discovered.

I will end my talk by demonstrating the roadmap of my future research. Driving questions include how the cell coordinates the assembly of complex macromolecular machinery (e.g., divisome) with the environment-dependent growth, and how the cell spatially organizes the essential cellular processes that define the primary structure of physiological control.

Short Bio

Fangwei Si received a B.Sc. in Mechanics from Peking University in 2009. In 2015, He received a Ph.D. in Mechanical Engineering from Johns Hopkins University where he studied the biomechanics of cell division and cell shape supervised by Dr. Sean Sun. Currently, he is a postdoctoral researcher in Dr. Suckjoon Jun’s lab at UC San Diego to study mechanisms of bacterial cell-size control by identifying general principles via quantitative measurements. He believes that the principle-driven approach is now transforming biology into a more quantitative field, which is reminiscent of the 17th- and 18th-century physics during the scientific revolution.

Host: BingKan Xue