UC San Diego

Bacteria often encounter stress conditions, where cells need to address conflicting demands. For instance, a bacterium may need to save resources and use energy to defend simultaneously. Moreover, many, if not all, cellular processes are dynamic: oscillatory behaviors, like cell cycle regulators, or transient pulses, like neuronal activities, are much common than one may expect. How can a cell coordinate multiple and dynamic cellular processes to establish a right response? This dissertation thesis attempts to account these questions focusing on its dynamic characteristics. It mainly consists of two parts: studies in communities, namely biofilms (Chapters 2-4), and in individual cells (Chapters 5-6).

In the first part, three examples of how Bacillus subtilis biofilm cells deal with conflicting demands are considered. Utilizing time-lapse imaging techniques, we dissected coupling mechanisms under nitrogen stress. For instance, biofilm cells couple nitrogen metabolism among neighbors, which could account for an unexpected emerging pattern across more than 100 times of a cell-length scale (Chapter 2). Based on this insight, we could also explain the oscillatory growth of 2D biofilm in a microfluidic device: metabolic codependence between interior and exterior cells of a biofilm results in the oscillatory growth. It is noteworthy that biofilms exerting this behavior are more resistant to external attacks (Chapter 3). The discovery was then expanded to understand multiple biofilm cases. We found that nearby biofilms coordinate their growth and nitrogen consumption dynamics, which enhances overall growth (Chapter 4).

In the second part, two studies are presented as examples of how dynamic processes are coordinated at the single-cell level. By investigating B. subtilis sporulation, we demonstrated that chromosomal arrangement of two key regulators ensures the coordination between a cell cycle and a cellular differentiation under starvation (Chapter 5). We could also show that two of the most ancient and fundamental properties of a cell, ribosomes and membrane potential, are coupled through magnesium ions under ribosome-perturbing stresses (Chapter 6). Taken together, these examples emphasize an interesting concept that can be applied across multiple scales: cells can coordinate their cellular processes not through a specific master regulator, but through the dynamic characteristics of the interactions.