Research

Effective coordination of cellular processes — such as division, motility, and metabolism — is critical to ensure the competitive growth of microbes. Pivotal to this coordination is the appropriate allocation of cellular resources between protein synthesis (e.g., growth) the metabolism needed to sustain it. But how can a cell – which is not much more than a watery bag of proteins – make such a decision? As a postdoc, I developed and experimentally tested mathematical models which provided one solution: cells encode a biochemical feedback loop which controls when (and where) proteins are made in response to how much energy is being generated via metabolism. This regulatory system imposes interesting constraints on how fast cells can grow, how fast they can adapt to changing conditions, and what different physical shapes cells can adopt.

All living things share a fundamental ability: they sense changes in their environment and respond accordingly. This adaptation happens across vastly different timescales—from nanosecond protein movements to billion-year evolutionary processes—but the underlying physics remains surprisingly consistent. During my PhD, I focused on one feature common to all life: the regulation of gene expression. Using simple thermodynamic models, I characterized how protein “switches” called allosteric repressors respond to environmental signals, and discovered that nearly 500 different measurements could be collapsed onto a single curve defined by a quantity we termed the “free energy” of the regulatory architecture. This framework proved powerful enough to predict how mutations alter repressor function—even allowing me to predict the behavior of double mutants based solely on single mutant data. I then extended these models to show they could predict gene expression across different growth conditions, revealing that the same thermodynamic principles govern molecular responses across multiple physiological states.

Microbial communities harbor a puzzling form of diversity: genetically nearly-identical bacterial strains routinely coexist in shared environments, even when conventional ecological theory predicts one should outcompete the others. During my postdoc (and beyond), I’ve worked on theoretical approaches to better understand competition in microbial ecosystems. Working with Akshit Goyal, we explored mechanisms ranging from subtle differences in nutrient preferences and metabolic trade-offs to the role of evolutionary processes like horizontal gene transfer in generating new strains. This work revealed a fundamental challenge to ecological theory: the finer we look at microbial communities, the more coexistence we find—the opposite of what traditional niche theory predicts. Resolving this paradox will require new theoretical frameworks and creative experiments that bridge the gap between genetic similarity and ecological divergence.