2026 Thiol-Based Redox Regulation and Signaling Gordon Research Conference and Gordon Research Seminar - PROJECT SUMMARY This proposal requests support for the 10th meeting of the biennial 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 11-12 (GRS) and July 12-17 (GRC), 2026. Regulation of protein function through the post-translational modification of specific cysteine residues (thiol oxidation) plays an important role in cellular adaptation to local and global changes to endogenous and environmental oxidants. A key challenge for the redox-signaling field is to understand how thiol-based signaling mechanisms are integrated into cellular redox homeostasis and how these events facilitate communication between molecules, organelles, cells, and tissues to initiate and coordinate a specialized biological outcome. Significant emphasis for the 2026 meeting will be placed on an exploration of a wider range of cysteine thiol chemistry placed within a cellular context of other, often competing, oxidative or acyl modifications, some of which derive from environmental exposures, and contribute to cancer, aging and the progression of disease. In addition, we will discuss new insights into how cellular redox status impacts metabolic disease and new mathematical and analytical approaches to understand how redox gradients or “waves” impact the spatial and temporal aspects of signaling. A long-term objective is to use this new information to develop diagnostics and therapeutics for a wide range of redox-associated diseases that impact public health. This meeting provides a unique forum for extensive and immersive interaction among chemists, biologists, structural biologists and redox tool-builders, interested in a range of animal and cellular model systems, with clinical researchers and physicians focused on disease processes. While the thematic area of the conference is intentionally broad, its relevance to specialized NIH institutes is highly significant. Not only is redox toxicity proposed as a primary driver of chemically-induced pathology in humans, notably in aging and age-associated diseases, protection from these pathologies by “supersulfides” holds considerable promise. In keeping with the GRC tradition, the 2026 meeting will highlight presentations that emphasize unpublished work, creating a distinctive intellectual experience that enhances the excitement of the meeting. Investigators new to the meeting, junior investigators and graduate and post-graduate trainees will be welcomed. The associated GRS will provide a more intimate forum where graduate and postdoctoral trainees present their research to their peers, while receiving constructive comments from a few senior investigators who serve as mentors. We intend that the GRS/GRC meetings will attract and increase retention of junior scientists in the field of redox biology. We anticipate that the GRC will enhance the education of researchers at all career levels, generate new ideas and collaborations aimed at understanding thiol-based redox regulation and dysfunction, and enable future progress in the prevention, detection, and treatment of a wide-range of human diseases associated with perturbations in redox homeostasis.
