Toxic aggregation-prone proteins are thought to play an important role in several age-related neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. To understand disease mechanisms, we aim to uncover the cellular pathways that regulate disease-protein toxicity, aggregation, and spreading. We combine C. elegans genetics with cell-biological and biochemical tools to monitor aggregation, toxicity, and cell-to-cell transmission of aggregation-prone proteins in living worms. We aim to translate our findings in worms to cell-culture models, mice and patient-derived cells. Our studies will provide a molecular understanding of how human cells cope with protein damage in health, aging and disease.