DSSS - Experimental Evolutionary Physiology: Using Organoids to Understand How Organs Adapt and Evolve

Understanding what makes human biology unique requires comparing our physiology with other species in experimentally tractable systems. Over the past decade, we have developed advanced organoid platforms that model human organ development and physiology in vitro, with a focus on organs at environmental interfaces—the gastrointestinal tract and sensory systems like the eye. These models integrate epithelial, stromal, neural, immune, and microbial components, and we use single-cell genomics, high-content imaging, and perturbations to benchmark their physiological relevance. We are now extending this approach to understand recent human evolution by developing organoid systems from diverse humans, great apes, and other primates, alongside primary tissue comparisons. This allows us to identify human-specific adaptations and understand how our recent evolutionary history—including dietary shifts, pathogen exposure, and other environmental change—shapes modern disease susceptibility. More broadly, this approach can be expanded to animals with interesting and extreme physiological adaptations, making organ-level evolutionary questions experimentally tractable across the tree of life. I will present recent work on human evolutionary physiology and discuss the potential and current limitations of stem cell, organoid, and bioengineering technology to transform comparative biology.