Cold Spring Harbor Laboratory Conference on Protein Homeostasis in Health and Disease April 21 – 25, 2020 ABSTRACT This proposal is a request for financial support for a meeting on PROTEIN HOMEOSTASIS IN HEALTH AND DISEASE to be held at Cold Spring Harbor Laboratory from April 21 – 25, 2020. This meeting is the premier international forum for presentation of new results in this area, and is attended by representatives from virtually every major laboratory in the field. The explosion of new information on how the folded state of proteins is acquired and maintained in vivo and the relevance of this process to healthy aging and risk for diseases of neurodegeneration, cancer, and metabolism guarantees an excitement and urgency of this meeting. Because of the recent developments on stress signaling in aging and disease, we will open the meeting with this new session followed the next day with a session on protein aggregation in aging and neurodegenerative diseases and then closing the meeting with a session on correcting proteostasis in aging and disease. Additional sessions will address the relationship between protein synthesis, folding, translocation and degradation by discussing the molecular mechanisms of chaperone function, degradative mechanisms and on spatial quality control and organellar proteostasis. The meeting will also introduce another new session on stress granules and phase transitions that has brought many new concepts on stress physiology, regulatory biology and novel forms of macromolecular interaction. These fundamental questions are at the heart of biology of proteostasis that will be complemented by the sessions on aging and proteostasis failure in diseases of protein misfolding including Alzheimer's disease, ALS, Parkinson's disease and Huntington's disease. The themes of aging, proteostasis failure, and diseases of protein misfolding are well integrated throughout the meeting, and emerging principles on protein client interactions and alternate protein conformations will be predominantly displayed. The diverse protein quality control strategies used by compartments of the cell to ensure the integrity of the secretory and organellar pathways during times of protein folding stress will be represented by emerging topics on spatial quality control within a cell. The field of heat shock proteins and molecular chaperones has grown exponentially and draws interest not only from traditional scientific disciplines in the basic sciences but also from diverse areas of biomedical research including neurodegenerative disease, infectious diseases, cancer, heart disease and aging. The meeting will have eight lecture sessions, two poster sessions, two rapid-fire presentation sessions, and a panel discussion on scientific publishing. The sessions include: 1) Integrative stress signaling in aging and disease, 2) Chaperone mechanisms I, 3) Protein aggregation in aging and neurodegenerative diseases, 4) Clearance mechanisms, 5) Chaperone mechan...