We studied how the physical organization of bacterial cells changes under stress and during DNA replication. In one line of work, we found that during nitrogen starvation, bacteria used the polymer polyphosphate to reorganize their internal environment. When cells could not make polyphosphate, their interiors became dramatically more fluid: molecules and chromosomes moved much faster, the DNA became less compact, and energy levels increased. These effects occurred specifically under nitrogen starvation, revealing that polyphosphate helped tune the cell’s physical state in a context-dependent way, beyond its traditional role as an energy or phosphate store. In parallel, we investigated how bacteria organize the machinery that copies their DNA. Using live-cell imaging, we found that the two DNA-replicating machines could either stay together or move apart, depending on how the chromosome was arranged. When chromosome alignment was disrupted or conflicts with gene expression arose, the two replication machines truly separated. Together, our findings showed that bacterial chromosome dynamics actively shape cellular organization and function, resolving long-standing debates about how replication is structured inside cells.
We investigated how mitochondria organize their structure, genetic material, and gene expression, and found that physical considerations play a central role in mitochondrial function. First, we discovered that mitochondria divide in two distinct ways with different purposes. When division occurred near the ends of mitochondria, it separated damaged components into small fragments that were targeted for recycling, supporting quality control. When division occurred at the middle, it produced healthy new mitochondria, enabling growth and proliferation. These two modes relied on different molecular partners, revealing how cells independently regulate mitochondrial repair versus biogenesis—an insight relevant to many diseases linked to mitochondrial dysfunction.
We also uncovered how mitochondria organize RNA needed for gene expression. Using super-resolution imaging, we showed that mitochondrial RNA granules are tiny, fluid-like compartments with dense RNA cores surrounded by proteins. These granules exchanged components rapidly and could fuse, behaving like liquid droplets. Their even distribution depended on normal mitochondrial movement and division; when these dynamics were disrupted, granules clustered abnormally. This demonstrated that mitochondrial shape changes are essential for properly distributing the machinery that expresses mitochondrial genes.
Finally, we identified a physical mechanism that spaces mitochondrial DNA evenly along the organelle. We found that mitochondria frequently undergo a reversible shape instability called pearling, in which tubules briefly form evenly spaced beads. This process pulled DNA clusters apart and positioned them at regular intervals, ensuring reliable inheritance and uniform gene expression. Calcium triggered pearling, while internal membrane structure preserved the spacing afterward. Together, our findings showed that mitochondrial organization emerges from dynamic physical processes, rather than fixed molecular scaffolds, revealing new principles underlying cellular health.
