From Protein Folding to Misfolding Disorders: The Importance of Maintaining Proteostasis over a Lifetime

The cellular proteome is constantly exposed to a wide variety of proteotoxic stress conditions. These include external stresses, such as elevated temperatures and radiation damage as well as physiological stresses encountered during cellular proliferation and differentiation, such as oxidative stress, or challenges to protein folding caused by inherited gene mutations. Moreover, a number of common stimuli, such as pharmacological agents, infection, and inflammation also negatively impact the cellular proteome. In all organisms, deployment of a comprehensive stress response is essential for the maintenance of protein homeostasis in response to proteotoxic stress. A hallmark of stressed cells and organisms is the increased synthesis of molecular chaperones that aid in the folding of nascent polypeptides and prevent protein misfolding and aggregation. Chaperones are also important for protein degradation and translocation of proteins across membranes as well as for the correct formation of macromolecular assemblies. The protein quality control and stress protection machineries require strict signaling modalities and transcriptional programs, many of which are altered in a number of disease states, including cancer, cardiovascular disease, metabolic disease (e.g., diabetes) and liver disease. Modulation of the stress response also plays a critical role in life-span regulation and aging-related disorders such as Alzheimer's, Parkinson's, Huntington's diseases as well as prion-based disease.

The Gordon Conference on "Stress Proteins in Growth, Development and Disease" will highlight the most recent advances in stress biology and biomedical research of stress-related diseases. Special emphasis is on a multitude of model systems that are being used to investigate stress sensing, signaling and regulation of gene expression, including epigenetic mechanisms. Cutting-edge work on spatial quality control and management of protein misfolding at the ribosome will be highlighted. Connections between compartmental protein folding status and disease will be explored. The Conference's collegial and scholarly environment encourages vigorous discussions of exciting developments related to several areas of stress research. The meeting also provides excellent opportunities for graduate students, postdoctoral fellows and junior group leaders to present their work either in posters or short talks. We will continue recent meetings innovations of poster teaser talks and career tables, and will be adding for the first time a Power Hour focused on women investigators in the field. The formal scientific program, limited attendance and organized but informal opportunities for interaction make this meeting a preeminent conference promoting deeper understanding of the versatile roles of stress proteins in human health, aging and disease.