of the parent project: In recent years, the field of bacterial cell-size control has received broad attention due to the discovery of the ?adder? principle by Christine Jacobs-Wagner?s lab and my lab. This phenomenological principle states that cells add constant size between birth and division regardless of cell size at birth. Until now, the vast majority of bacteria, budding yeast, and even some mammalian cell lines have been shown to follow the adder principle. This directly refutes the 50-year old checkpoint-based paradigm of cell-size control that cells should divide when they reach a fixed size. The goal of the funded parent award is to understand the mechanisms underlying the adder principle. So far, our research has revealed that the adder phenotype requires two general principles in biology (Si et al. 2019): (1) accumulation of division proteins (such as FtsZ in bacteria) to their threshold number (2) their balanced biosynthesis during cell elongation. Therefore, the adder principle is naturally robust to static growth inhibition, and these mechanistic principles further allowed us to ?reprogram? cell-size homeostasis in a quantitatively predictive manner in both Gram-negative Escherichia coli and Gram-positive Bacillus subtilis.
Cell size is intimately coupled with cell growth and the cell cycle, the fundamental process underlying both healthydevelopment(childhoodthroughadolescence)andpathologicdisease(disruptedcellularhomeostasis in old age, cancer). This proposal aims to establish a causative relationship between genome size, proteome composition, and cell size and, thus, a quantitative understanding of a process critically important to nearly everyaspectofhumanlife.
