Unlocking the Redox Code: Mapping the Molecular Mechanisms of Hypoxia Tolerance

Objective

"Hypoxia, the condition of inadequate oxygen availability, has profound implications for life on Earth. It contributes to biodiversity loss and is a key factor in many human diseases, including stroke and other chronic diseases, such as heart disease, cancer and neurodegenerative disorders, which are leading causes of death and disability in the EU. The URC-Hypoxia project aims to explore the molecular mechanisms that enable certain organisms, like the waxworm Galleria mellonella, to be resilient to hypoxia. By studying how these organisms survive hypoxia through the ""Preparation for Oxidative Stress"" (POS) adaptive response, the project seeks to characterize the molecular mechanisms underlying POS. This knowledge might be relevant in finding biomarkers and putative target molecules to improve hypoxia-related human diseases. The project will test the hypothesis that early reactive oxygen species (ROS) production under hypoxia triggers redox-sensitive signaling pathways, leading to POS as part of the cellular stress response. This will be explored using transcriptomics, proteomics, and oxidative modification mapping techniques. Key objectives include: (1) Characterizing anoxia tolerance in Galleria mellonella and identifying key windows for redox signaling events; (2) Quantifying ROS production and pinpointing redox imbalance; (3) Identifying transcripts, gene networks, proteins, and oxidative modifications involved in the hypoxia response; and (4) Testing the feasibility of targeting these mechanisms to enhance hypoxia resilience in human cells. The methodology employs advanced tools like mass spectrometry, RNA sequencing, and imaging techniques, leveraging the host institution (i3S) specialized scientific platforms. The project is expected to provide new insights into the molecular basis of hypoxia tolerance, which could lead to innovative treatments for hypoxia-related diseases. It aligns with EU health priorities by addressing chronic disease management."