This proposal requests support for the Fifth Gordon Research Conference, and second associated Gordon Research Seminar on Thiol-Based Redox Regulation and Signaling to be held at the Melia Golf Vichy Catalan, Girona, Spain on July 19-20 (GRS) / 20-25 (GRC) 2014. The subtitle of this conference, """"""""From Redox Biology and Chemistry to Aging and Associated Diseases,"""""""" reflects the focus of the upcoming meeting on the fundamental cellular processes that are governed by redox-based modifications of protein function, and on the dysregulation of these processes that occur during aging and its associated pathologies. Redox biology is an all-encompassing term that refers to the multitude of reduction and oxidation processes occurring in biological molecules. This Gordon conference focuses specifically on the redox regulation of protein function by modification of cysteine and methionine residues and on the agents that modulate the redox state of these residues. These include both cellular protein reductase and oxidase systems, and endogenous and exogenous reactive oxygen and nitrogen species - ROS and RNS, respectively that are sulfur-reactive. Thiol-based redox processes underlie many cellular processes that are altered during aging and associated diseases. These include protein oxidative folding and secretion, mitochondrial functions, oxygen, ROS and RNS sensing and signaling, ROS and RNS metabolism, DNA synthesis and gene expression. Given that aging and associated diseases are suspected to result from progressive breakdown of redox homeostasis, a better description of the redox components in cellular processes will help establish whether and how biological systems are susceptible to physiological alterations and disease development. This interdisciplinary conference is in its fifth cycle after four very successful meetings in the U.S. (2006 and 2012) and Italy (2008 and 2010). It will provide, as it has in the past, an important venue for the free exchange of ideas and methodologies among the chemists, biochemists, molecular and cell biologists, physiologists, and clinicians working on various aspects of the field. While the thematic area of the conference is broad-based, its relevance to aging and associated diseases (e.g., inflammation, protein aggregation diseases) and for understanding the molecular basis of human physiology and pathology is highly significant. By bringing together investigators with varied expertise in biophysical methods, bioinformatics and animal and cellular model systems, with clinical researchers and physicians focused on disease processes, the meeting is expected to further stimulate collaborations and catalyze scientific progress as has been exemplified by the successes of the previous meetings. For the second time, the GRC will be preceded by a Gordon Research Seminar (GRS) (July 19-20, 2014), which will provide an opportunity for graduate students and postdoctoral scientists to formally present research and engage in scientific discussions. We expect this to continue to attract and increase retention of young scientists to the field of redox biology and aging.
Many cellular functions rely on processes that involve changes in the oxidation status of particular molecules within the cell, and the dysregulation of these processes is a major component of the onset and progression of aging and age-related diseases including cancer, cardiovascular and neurodegenerative diseases. A particular protein reactive group, the side-chain thiol (-SH) of the cysteine residue serves as a molecular switch to regulate multiple cellular functions and to combat oxidative damage, but is also highly susceptible to oxidative stress-induced damage. This conference brings together chemists, biochemists, molecular biologists, and clinicians who will exchange novel knowledge and ideas centered on the molecular details of the nature, location and timing of redox changes at thiols during normal and age-related pathological processes, and on how this knowledge will be translated into novel therapeutic strategies.