Paralogue-Dependent Control of Redox State and Mitochondrial Dynamics in Stem Cells

• Applicant: Professorin Dr. Maria Felicia Basilicata
• Subject Area: General Genetics and Functional Genome Biology ; Developmental Biology ; Cell Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575163598

Rare neurodevelopmental disorders (RDs) frequently stem from mutations in genes that encode chromatin-associated proteins, the molecular machinery that controls how DNA gets packaged and accessed within cell nuclei. Most of the RDs manifest with neurological symptoms, including intellectual disability, global developmental delay, and autism spectrum disorders. Uncovering the molecular mechanisms underlying these disorders and their convergence on neurological susceptibility is essential for identifying common pharmacological pathways, which potentially can lead to more effective and personalized treatments. While these RDs are traditionally conceptualized as defects in gene regulation, chromatin dysfunction has the potential to perturb cellular metabolism. This metabolic dimension of chromatinopathies represents an underexplored but potentially central aspect of disease pathophysiology. Using embryonic mouse stem cells as a model, we aim to characterize and analyze the molecular principles of this interplay. In our work, we have discovered a molecular "switch" that could play a central role in the regulation of nuclear acetylation and metabolism in the context of RDs. We will investigate the mechanisms underlying the relationship between histone acetylation and metabolism through integrated genetic, metabolomic, and genomic approaches. Our research focuses on understanding how this switch regulates cellular homeostasis and how its dysfunction contributes to the complex phenotypes observed in rare neurodevelopmental disorders. Our findings may pave to novel therapeutic strategies for conditions in which metabolic symptoms remain underrecognized.

• DFG Programme: Research Grants