Margaret Lockwood

Humans harbor vast microbial ecosystems that profoundly influence health. Bacteria in our digestive system, the gut microbiome, perform critical functions like digesting fiber and producing vitamins. This ecosystem develops during infancy, particularly during weaning when diet shifts from milk to solid food, and shapes immune maturation. Disruptions during this window are linked to allergies, diabetes, and obesity. Despite the importance of community structure at weaning, we cannot predict how these communities assemble and function. Current approaches rely on expensive animal models, limiting hypothesis testing. Predictive computational models would revolutionize personalized medicine. My research addresses this gap by developing a computational framework to predict and modify microbiome behavior during weaning. I will build a spatiotemporal digital twin of the infant gut microbiome by integrating genome-scale metabolic models with experimental validation. I will use constraint-based flux balance analysis in frameworks like COMETS or MICOM to simulate thousands of metabolic interactions among bacterial species. I will solve thousands of coupled differential equations across spatial grid points using high-performance computing. The computational challenge of this project lies in the combinatorial explosion of possible metabolic states — exploring this parameter space demands parallel computing and optimization algorithms, with potential future extension to quantum computing to break the curse of dimensionality. I will leverage machine learning to accelerate predictions by training neural networks on simulation outputs to identify patterns linking diet, microbial cross-feeding, and immune signaling. With this hybrid biophysics-ML approach, I will rapidly test hypotheses about dietary components that drive healthy immune system maturation. I will validate model predictions against metagenomic and metabolomic data from organoid models and patient data. The impact is transformative: (1) identifying critical microbiome transitions during weaning that drive immune system development, and (2) discovering targeted dietary interventions that promote healthy microbiome assembly in at-risk infants during this critical developmental window.