This proposal requests support for the Gordon Research Conference (GRC) and associated Gordon Research Seminar (GRS) on Thiol-Based Redox Regulation and Signaling to be held at the Rey Don Jaime Grand Hotel, Castelldefels, Spain on July 14-15 (GRS) and July 15-20 (GRC), 2018. The meeting focuses on the fundamental cellular signaling pathways that are governed by redox modifications of proteins, and on the dysregulation of these processes that occurs during aging and its associated pathologies. Redox regulation of protein function is based on the unique chemistry of sulfur atoms present in cysteine and methionine residues. One key challenge is to understand how oxidative protein modifications relevant to redox signaling are generated with specificity. Another key challenge is to understand the physiological and pathophysiological meaning of individual oxidative protein modifications. Central to this challenge is the ability to measure these modifications and their stoichiometry in vivo. This in turn requires rigorous understanding of sulfur and reactive species chemistry. We also need to understand how thiol modifications integrate and cross-talk with other kinds of signaling. The last two years have seen remarkable progress. Several new observations and tools allow to take a fresh look at long-standing conceptual and technical problems. The 2018 GRC will be timely and most useful for exchanging and discussing the newest developments in this rapidly changing field. It will bring together experts in redox chemistry, redox enzymology, cell biology, metabolism, ageing and cancer biology. This interdisciplinary conference is in its seventh cycle after six very successful meetings in the US (2006, 2012 and 2016), Italy (2008 and 2010), and Spain (2014). It will continue to provide an important venue for the free exchange of ideas and methodologies among 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 for understanding the molecular basis of human physiology and pathology related to the missions of NIA and NCI is highly significant. By bringing together investigators with varied expertise in biophysical methods, bioinformatics and animal and cellular model systems, with clinical researchers focused on disease processes, the meeting is expected to further stimulate collaborations and catalyze scientific progress as has been exemplified by the success of the previous meetings. For the fourth time, the GRC will be preceded by a Gordon Research Seminar (GRS), which will provide an opportunity for graduate students and postdoctoral scientists to formally present research and engage in scientific discussions. We expect to attract and increase retention of talented young scientists to the field of redox biology in aging and cancer research.
The function of many critical signaling proteins, including phosphatases, kinases and transcription factors, is regulated by dynamic post-translational redox modifications of thiol groups, which serve as redox-sensitive molecular switches to adapt protein function and cell signaling to metabolic changes and stress situations. The dysregulation of redox signaling pathways is increasingly recognized as a major component in the progression of aging and age-related disease. This conference brings together chemists, biochemists, molecular biologists, cell biologists and clinicians to exchange the newest findings and concepts related to the nature, location and timing of thiol-based redox changes in aging and age-related pathological processes, and to discuss novel therapeutic strategies.
