P07 - Gene regulation

Decoding vulnerability of sensorimotor neurons to neuroinflammation

Damage and dysfunction of neurons are defining hallmarks of inflammatory diseases of the central nervous system, including multiple sclerosis (MS). While MS and related disorders have long been characterized by focal inflammatory brain injury, increasing evidence indicates that such lesions also provoke secondary neuronal loss and circuit dysfunction in connected regions. Among these, specific neuronal subtypes—particularly cortical projection neurons—appear highly vulnerable, yet the molecular, cellular, and genomic mechanisms that translate localized inflammation into widespread neuronal degeneration remain poorly understood.

This project aims to dissect the sequential events and determinants of neuronal vulnerability and resilience following focal inflammatory brain injury. Using an experimental system that allows spatially precise induction of localized lesions, we will track how inflammatory activity propagates along axonal projections and alters neuronal and glial states over time. Combining single-cell and spatial transcriptomics with in vivo calcium imaging, electrophysiological recordings, and ultrastructural analyses, we will map subtype-specific stress responses, metabolic adaptations, and network-level remodeling processes. Integrating these datasets with genomic and transcriptomic information will further enable us to determine how genetic risk factors shape and predict neuronal response patterns to inflammatory stress.

By linking molecular signatures, structural alterations, and functional outcomes, this project will establish a comprehensive framework for understanding how focal inflammation drives remote neuronal degeneration. These insights will not only advance our understanding of MS pathogenesis but also provide generalizable concepts for neuroinflammatory and neurodegenerative diseases. Ultimately, the work aims to identify biomarkers and therapeutic targets that promote neuronal survival and resilience, bridging mechanistic insight with translational potential in precision neuroimmunology.