Building a Human Epiblast-Like Vulnerability Map of Germ-Layer Formation for Developmental Toxicology

• Applicant: Andrea Rossi, Ph.D.
• Subject Area: Toxicology, Laboratory Medicine ; Developmental Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 577885014

The Developmental Origins of Health and Disease (DOHaD) concept highlights that early life environmental exposures significantly influence later disease susceptibility. While this relationship is recognized, the underlying human developmental pathways and their intrinsic vulnerabilities to specific environmental stressors, especially during fundamental processes like germ layer formation, are still largely unknown. Our project seeks to bridge this critical knowledge gap by creating a human epiblast-like vulnerability map of germ-layer formation for developmental toxicology. Utilizing pooled CRISPR loss-of-function screens in a standardized human iPSC line (KOLF2.1J–Cas9–eGFP) and integrating a machine-learning based QC system (hiPSCore), the project will generate stage-resolved gene essentiality maps for ectoderm, mesoderm, and endoderm. These intrinsic vulnerability maps will be systematically annotated with curated pollutant–gene/pathway interactions from databases like CTD and ToxCast/Tox21, creating a human vulnerability–pollutant atlas. A tightly scoped exposure pilot with well-characterized developmental toxicants will benchmark the atlas's predictive value. This work will provide a human-relevant, mechanistic framework for hazard prioritization and improved risk assessment in environmental health, reducing reliance on animal testing.

• DFG Programme: Research Grants