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

Project description

Research explores how certain organisms naturally survive low oxygen conditions

Low oxygen levels, or hypoxia, pose serious challenges to life, contributing to biodiversity loss and major human diseases including stroke, cancer, and heart diseases. Certain organisms, such as the waxworm Galleria mellonella, have evolved unique ways to survive hypoxia. With the support of the Marie Skłodowska-Curie Actions programme, the URC-Hypoxia project focuses on understanding the resilience of this organism to hypoxia by studying a process called preparation for oxidative stress. In this adaptive response, early oxygen imbalances trigger redox-sensitive signalling pathways. Researchers will use mass spectroscopy, RNA sequencing, and imaging techniques to identify key genes, proteins, and molecular pathways involved in hypoxia adaptation. The proposed research could help uncover potential targets for treating hypoxia-related diseases.

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."

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

I3S - INSTITUTO DE INVESTIGACAO E INOVACAO EM SAUDE DA UNIVERSIDADE DO PORTO
Net EU contribution

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€ 207 183,12
Address
RUA ALFREDO ALLEN 208
4200-135 PORTO
Portugal

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Region
Continente Norte Área Metropolitana do Porto
Activity type
Research Organisations
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Total cost

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