Description du sujet de thèse

Dihydrouridine and Cellular Adaptation to Stress: Exploring the Links Between Redox Metabolism and the Regulation of Protein Synthesis

Contexte de travail

Scientific Context:
RNA plays a central role in protein synthesis, a fundamental biological process. Chemical modifications of RNA fine-tune its structure and function, thereby influencing gene expression. Among these, dihydrouridine (D) is a conserved but poorly understood modification, mainly found in tRNAs. This project explores the hypothesis that D acts as a redox-sensitive regulator of translation. Combining organic chemistry, enzymology, and structural biology, the goal is to investigate how redox metabolism (e.g., NADPH levels) modulates D levels and impacts cellular stress responses. Through the development of innovative chemical tools, including novel labeling strategies, epitranscriptomic probes, and potential inhibitors, this research will provide insights into how RNA modifications contribute to stress adaptation. In the long term, this could lead to therapeutic approaches targeting D in diseases linked to redox imbalance, such as cancer, metabolic disorders, or neurodegeneration.

PhD Objective:
The aim of this PhD project is to explore the role of dihydrouridine (D) as a potential redox sensor in the regulation of translation—an innovative and largely unexplored concept in RNA biology. The project focuses on developing novel chemical tools and interdisciplinary approaches, combining organic synthesis, enzymology, and structural biology, to label, map, and modulate D-modified RNA sites across the transcriptome. This thesis seeks to uncover fundamental mechanisms of RNA modifications and their implications in oxidative stress-related cellular processes and diseases.

Candidate Profile :
• Master's degree (M2) in Organic Chemistry
• Experience in a synthetic chemistry lab (M1/M2 internship required)
• Strong interest in biochemistry and interdisciplinary research
Application Process:
Please send the following documents by email:
CV, Cover letter, Academic transcripts, (Optional but recommended) Letters of recommendation from internship supervisors.