"Living cells have evolved a complex network of signaling pathways and adaptative responses which enable them to survive and adapt to diverse environmental challenges. Our increasing understanding of the molecular mechanism of cell signaling has revealed that reactive oxygen species (ROS) and reactive nitrogen species (RNS) act as signaling molecules to transfer extracellular or intracellular information and elicit specific responses. ROS/RNS mainly act through a set of reversible post-translational modifications (PTMs) of thiol residues on proteins among which nitrosylation and glutathionylation have emerged as key elements playing a major role in numerous fundamental cell processes and are implicated in a broad spectrum of human diseases. Emerging evidence suggests the existence of an intricate network of redox signaling pathways with a complex crosstalk between the different types of redox modifications. A specific pattern of redox-based protein modifications likely constitutes a molecular language that allows to trigger specific responses in response to the input signal. The aim of this project is to investigate, using an innovative proteomic technology, the temporal and qualitative dynamics of redox-based PTMs in vivo. The method will allow qualitative and time-resolved detection of nitrosylation and glutathionylation that will be analyzed simultaneously and specifically from each sample. This technology will be combined to bioinformatics modeling to unravel the role of redox-based PTMs associated with the responses to diverse physiological conditions or with different genetic backgrounds in two model unicellular eukaryotes: the yeast S. cerevisiae and the green alga C. reinhardtii. By providing a method to understand the dynamics of redox-based PTMs, this project is expected to profoundly modify our knowledge of cell signaling mechanisms and thereby have a high impact both for fundamental and biomedical research."
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