Dissecting the molecular mechanism and functional role of 3D genome regulation by nutrients through RNA Pol I: a role in aging?

• Applicant: Daphne Selvaggia Cabianca, Ph.D.
• Subject Area: General Genetics and Functional Genome Biology ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559907625

Chromatin architecture is a fundamental modulator of genome function that is regulated in response to developmental cues. Environmental stimuli can also impact on chromatin state and function. However, how the environment shapes 3D chromatin organization and what consequences this has for cell and organismal function remains largely unknown. Very recently, my group identified the first large-scale spatial reorganization of the genome induced by fasting (short term lack of nutrients) in the multicellular organism C. elegans. Surprisingly, we found that the key regulator is RNA Polymerase I, which acts downstream of the nutrient-sensing pathway mTOR to shape the spatial organization of the whole genome in response to nutrients, specifically in intestinal cells. However, fundamental mechanistic and functional aspects of the 3D genome regulation by nutrients through RNA Pol I remain unresolved: How does RNA Pol I, which specifically acts within a defined nuclear compartment-the nucleolus- regulates 3D genome architecture at large? What are the consequences for gene expression and tissue function? Notably, mTOR, fasting, and RNA Pol I are all implicated in regulating aging. Yet, whether they influence late-life phenotypes through the modulation of 3D genome architecture remains unexplored. In this proposal, we aim to address these fundamental questions.

• DFG Programme: Research Grants