北京大学定量生物学中心

学术报告

题 目: Bacterial Replication Initiation as Precision Control by Protein Counting

报告人: Haochen Fu, Ph.D.

Department of Physics, UC San Diego

时 间: 9月19日（周二）10:00-11:00

地 点: 吕志和楼B101

主持人: 林杰 研究员

摘 要:

Balanced biosynthesis is the hallmark of bacterial cell physiology, where the concentrations of stable proteins remain steady. However, this poses a conceptual challenge to modeling the cell-cycle and cell-size controls in bacteria, as prevailing concentration-based eukaryote models are not directly applicable. In this study, we revisit and significantly extend the initiator-titration model, proposed thirty years ago, and explain how bacteria precisely and robustly control replication initiation based on the mechanism of protein copy-number sensing. Using a mean-field approach, we first derive an analytical expression of the cell size at initiation based on three biological mechanistic control parameters for an extended initiator-titration model. We also study the stability of our model analytically and show that initiation can become unstable in multifork replication conditions. Using simulations, we further show that the presence of the conversion between active and inactive initiator protein forms significantly represses initiation instability. Importantly, the two-step Poisson process set by the initiator titration step results in significantly improved initiation synchrony with CV ～ 1/N scaling rather than the standard 1/√N scaling in the Poisson process, where N is the total number of initiators required for initiation. Our results answer two long-standing questions in replication initiation: (1) Why do bacteria produce almost two orders of magnitude more DnaA, the master initiator proteins, than required for initiation? (2) Why does DnaA exist in active (DnaA-ATP) and inactive (DnaA-ADP) forms if only the active form is competent for initiation? The mechanism presented in this work provides a satisfying general solution to how the cell can achieve precision control without sensing protein concentrations, with broad implications from evolution to the design of synthetic cells.

报告人简介：

Haochen Fu obtained his B.S. from Peking University in Physics and joined Dr. Suckjoon Jun’s lab at University of California, San Diegon for his PHD research in 2020, working on bacterial physiology. He mainly focuses on experiments and theory about E. coli DNA replication initiation.