Dissecting early-life immunity in gut homeostasis, tolerance, and dysregulation using foundation models

With this fellowship, I will leverage recent advances in foundation modelling and unique multimodal single-cell and spatial datasets to develop DELIGHT-FM, the first gut-specific, multimodal, and developmentally aware foundation model. Unlike existing generalist approaches, DELIGHT-FM will explicitly capture intestinal tissue architecture, evolving niches, and immune colonization across developmental stages, transforming descriptive atlases into predictive, mechanistic insights. The project has three objectives: (i) build and validate a biology-first gut foundation model integrating transcriptomic, epigenomic, and spatial modalities; (ii) use model-derived features to define how mucosal tolerance is imprinted during healthy development; and (iii) apply in silico perturbations to identify disrupted trajectories in preterm infants and predict the minimal molecular or spatial changes needed to restore immune balance. This pioneering approach will provide the first holistic framework of human intestinal immune maturation, establish new strategies for biomarker and therapeutic discovery in neonatal disease, and deliver an open, reusable foundation model resource for the community. Through this fellowship, I will gain access to cutting-edge foundation model expertise in the Mahmood group, alongside comprehensive single-cell datasets and workflows in the Simmons and Antanaviciute groups, advancing both gut biology and digital medicine with broad implications for neonatal health, precision medicine, and the next generation of AI-driven biology.