Seminar: Engineering Fluorescence-Based Synthetic Biology Tools to Interrogate Gut Ecosystem Biogeography

Abstract: The human gut is a dynamic ecosystem where physical conditions such as oxygen levels and solute concentration (osmolality) strongly influence microbiota composition and function, ultimately shaping host health. Despite their importance, conventional approaches to studying gut environments rely on homogenized fecal samples, overlooking localized, real-time signals that drive microbial behavior. To address this, my PhD research focuses on developing in vivo bacterial biosensors that report on gut environmental conditions with single-cell resolution. We engineered new synthetic biology tools for the gut commensal Bacteroides thetaiotaomicron, including repressible promoters, modular transcriptional reporters, and novel genomic integration methods. Using these tools, we created fluorescent biosensors for two key stressors in the gut: osmolality (a proxy for malabsorption) and oxidative stress (oxygenation and reactive oxygen species). In mouse models of malabsorption and colitis, these biosensors successfully detected altered gut conditions and revealed spatial and temporal variations not captured by standard measurement methods. This platform offers a new lens for studying gut physiology, bridging synthetic biology, microbial ecology, and host–microbe interactions to support the development of microbiota-based diagnostics.