Glycosylation as a Regulatory Code in Human Brain Development and Disease

• Applicant: Dr. Maria Veronica Pravata, Ph.D.
• Subject Area: Developmental Neurobiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 574868899

The human brain develops through tightly regulated processes. While genetic and transcriptional programs have been well studied, the role of post-translational modifications -particularly glycosylation - remains largely unexplored. Glycosylation, the enzymatic addition of sugar chains to proteins, can alter protein stability, localization, and interactions. Yet its contribution to early brain development, species-specific traits, and disease is still poorly understood. This project investigates the role of glycosylation in human cortical development at molecular and cellular levels. Using brain organoids derived from human and non-human primate stem cells, we will map cell type-specific glycosylation patterns and identify evolutionarily divergent glycoenzymes. This will help reveal how glycosylation supports neural development and how evolutionary changes in this layer may have shaped the human brain. In parallel, we will explore glycosylation’s role in disease. We will focus on enzymes linked to congenital disorders of glycosylation (CDG) - severe neurodevelopmental syndromes with poorly defined mechanisms - and on enzymes genetically associated with schizophrenia. By combining CRISPR interference, prime editing, single-cell transcriptomics, and glycoproteomics, we will dissect how these enzymes affect neural progenitors and developmental trajectories. This research will clarify the developmental functions of glycosylation and bridge insights from evolution and disease.

• DFG Programme: Emmy Noether Independent Research Groups