Title: Nuclear proteostasis in health and disease: novel concepts in protein quality control
Abstract: My career is dedicated to elucidating the mechanisms that maintain proteome balance (proteostasis) and to uncovering toxicity pathways triggered by aggregation-prone proteins. A healthy proteome is essential not only for sustaining cellular functions but also for preventing the accumulation of aberrant protein species. When proteostasis collapses, misfolded proteins can form amyloids and other toxic assemblies, hallmarks of numerous age-related neurodegenerative disorders. During my PhD, I investigated the essential and ubiquitous N-terminal methionine excision pathway and demonstrated its critical role in maintaining redox homeostasis and proteostasis in both plants and human cells. This early work sparked my interest in proteostasis and related processes. In my postdoctoral research, I advanced our understanding of how aggregation-prone proteins perturb cell physiology, particularly in distinct subcellular compartments. A major contribution was the discovery that the nucleolus, best known for its role in ribosome assembly, also functions as a protein quality control compartment with unique chaperone-like properties. As a permanent researcher at the Institute for Integrative Biology of the Cell (I2BC), I now focus on nuclear toxicity pathways and nuclear-specific protein quality control systems. By combining in vivo and in vitro approaches, my team aims to dissect the molecular determinants of nucleolus-associated quality control and its broader implications for cellular resilience. Alongside these scientific contributions, I have been committed to mentoring students at all levels, fostering independence, critical thinking, and a collaborative research environment.