Support for research on the Proteostasis of Aging Biology

Protein misfolding and aberrant cell stress responses are increasingly recognized as a condition and likely basis of hundreds of human diseases, known collectively as protein conformational diseases. These include neurodegenerative diseases, type II diabetes, metabolic pathologies, and cancer. Imbalanced proteostasis is accelerated during aging and contributes to instability of the proteome and failure of the cellular quality control machinery to protect against the toxic consequences of damaged proteins. In the cellular context, misfolding leads to aberrant protein and membrane interactions, mislocalization, aggregation, and improper degradation, ultimately affecting the availability of functional proteins essential for cellular robustness and organismal health. To address these questions, we are interested in: (1) the regulation and functional properties of chaperone networks and cell stress responses to detect damaged proteins and to protect against misfolding and aggregation, (2) establishing how the proteostasis network maintains a healthy proteome in the face of stress, aging, and disease, (3) understanding how cell autonomous and cell non-autonomous signals ensure balanced tissue function, and to prevent local proteotoxic damage from compromising organismal lifespan, and (4) development of small molecules as chemical-genetic tools to restore proteostasis in health and disease.