Cold Spring Harbor Laboratory Conference on Protein Homeostasis in Health and Disease April 17 – 21, 2018 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 17 – 21, 2018. 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 diseases of neurodegeneration, cancer, and metabolism guarantees an excitement and urgency of this meeting. Because of the recent developments that have identified the ribosome at the origin of protein folding, we will have a new session on this topic and another new session that emphasizes emerging quality control mechanisms. The relationship between synthesis, folding, translocation and degradation will be addressed through sessions on molecular mechanisms of chaperone function, degradative mechanisms and on spatial quality control and organellar proteostasis. These fundamental questions are at the heart of biology and will be complemented by sessions on aging and proteostasis failure, and how this establishes the risk for 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 will be 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, a rapid-fire presentation session, and a panel discussion on scientific publishing. The proposed sessions include: 1) Proteostasis at the ribosome and protein folding, 2) Chaperone mechanisms I, 3) Novel mechanisms of quality control, 4) Degradation mechanisms, 5) Chaperone mechanisms II, 6) Aging and pathogenic aggregation, 7) Organellar proteostasis and spatial quality control, and 8) Proteostasis failure and disease. Each session will consist of eight to nine oral presentations and will be chaired by an invited speaker. A maximum of two additional speakers will be pre-invited per session and the remainder will be selected from submitted abstracts. This balance of talks allows the meeting to feature presentations by leading scientists, to be responsive to exciting new developments, and to encourage diverse participation that recognizes new investigators.

Cold Spring Harbor Laboratory Conference on Protein Homeostasis in Health and Disease April 17 –21, 2018 PROJECT NARRATIVE Proteins are composed of polymers of amino acids (or polypeptides) and execute essential tasks in all living organisms. Protein function is critically dependent on the folding of their constituent polypeptides into active three-dimensional objects through the interactions of molecular chaperones. Protein homeostasis is achieved by balanced synthesis, folding, translocation and degradation of proteins. Experimental evidence accumulated in the recent past has revealed that failure of this process (protein misfolding) leads to some of the most devastating diseases affecting humanity. The latter include common neurodegenerative disorders, such as Parkinson's Disease and Alzheimer's Disease, common metabolic disorders such as Diabetes Mellitus and a host of other conditions liked to the aging process. The Cold Spring Harbor Meeting on Protein Homeostasis in Health and Disease brings together experts in diverse aspects of protein folding and the cellular response to protein misfolding. As such it serves as the premier clearinghouse for ideas on how to eventually translate the basic discoveries in the area to future treatments of recalcitrant diseases.