We study how bacteria survive stress and starvation — from the physics of individual cells to the collective behavior of microbial communities. Our goal is to understand what determines whether a cell lives or dies when energy runs out, and how these individual fates shape the stability and function of populations. We approach this problem by combining single-cell experiments, quantitative modeling, and synthetic biology to reveal the physical limits of life and to develop design principles for resilient microbial systems.
Single-cell physiology during stress
Most bacteria spend their lives in nutrient-poor and stressful environments rather than in steady exponential growth. Yet we still know surprisingly little about how individual cells fail under such conditions.
Using microfluidic time-lapse microscopy, we observe single cells as they die of stress. We previously showed that death under starvation is not a gradual decay but a catastrophic mechanical failure. When ATP levels fall, ion pumps stall, ions leak inward, water follows, and the cell envelope bursts. The figure below illustrates this process: healthy cells remain plasmolyzed, depolarizing just before lysis — a transition we can track in real time with the voltage-sensitive dyes.
We are now extending these approaches to other stresses, such as heat, oxidative, and osmotic challenges, to identify general biophysical modes of death. Together, these studies provide a biophysical framework linking molecular stress to survival outcomes.
Biophysical modeling of death processes
Parallel to the experiments, we build theoretical models that describe how physical parameters such as permeability, active pumping, and stochastic fluctuations control the dynamics of ionic balance inside the cell.
In the case of starvation, a simple differential equation captures the interplay between diffusive influx, active pumping, and noise, and predicts how cells cross from a metastable viable state into irreversible collapse. The lower figure shows simulated trajectories of intracellular solute concentration during starvation, and the corresponding pseudo-potential landscape: in starvation cells stochastically die in a single catastrophic failure.
Current work extends these models to describe failure under oxidative, pH, and temperature stress, laying the foundation for a unified physical theory of bacterial death.
From single cells to microbial communities
The same physical constraints that limit single-cell survival also shape the dynamics of microbial communities. Trade-offs between growth, survival, and metabolic flexibility force microbes into specialized roles, influencing coexistence and stability. We explore how stress reshapes interactions within communities. For instance, how some strains lyse and feed others, or secrete antimicrobial compounds when nutrients run out.
Our long-term goal is to translate these mechanistic insights into the design of synthetic consortia that remain robust under fluctuating conditions. Using automated pairwise culturing, time-lapse imaging, and metabolite profiling, we map stress-induced interactions and integrate them into predictive models. These principles will guide the construction of synthetic microbiomes with built-in resilience.
Approach and vision
Our lab combines quantitative microbiology, microfluidics, and theoretical modeling to bridge molecular mechanisms with emergent behavior. We believe that understanding the physics of how microbes survive and die will open new routes to control microbial ecosystems, engineer stable synthetic communities, and ultimately define the physical principles that limit life itself.
We welcome students and collaborators who enjoy connecting disciplines, physics and microbiology, experiment and theory, to uncover how living systems endure stress and persist in the face of failure.