Overarching Roles of O-GlcNAcylation In Genomic Architecture: molecular Mechanisms and physiopathological Impact

The ORIGAMI project investigates how O-GlcNAcylation, a reversible nutrient-sensitive post-translational modification, regulates chromatin folding and influences metabolic disorders and cancer. Despite its critical roles in transcription and cell signaling, its impact on 3D chromatin architecture remains poorly understood.

This multidisciplinary project combines molecular biology, glycobiology, biochemistry, and computational biology to uncover how O-GlcNAcylation links nutrient sensing to gene regulation and genome topology. Techniques include Hi-C for chromatin conformation mapping, proteomics and BioID for protein interactome analysis, multimodal Cut&Tag and RNA-seq for epigenomic and transcriptional profiling. Large-scale omics datasets from patient tumor samples will be integrated using machine learning and AI to identify regulatory networks related to disease pathways.

The PhD candidate will contribute to genome editing of iPSCs, development of organoid models, chromatin and O-GlcNAc profiling, and multi-omics data analysis across several work packages, gaining broad technical and analytical expertise.

The candidate will join a rich international scientific ecosystem:

The University of Lille is a top French research university excelling in life sciences, health, and interdisciplinary innovation. It hosts many internationally recognized labs in glycobiology, cancer biology, molecular biology, and data science. As part of the I-SITE initiative, it leads in European precision medicine and translational research, fostering partnerships across academia, clinics, and industry worldwide.

UGSF (Unité de Glycobiologie Structurale et Fonctionnelle) is a leading European glycobiology institute with ~150 researchers focused on structure-function relationships of complex carbohydrates and their roles in cancer, metabolism, infection, and diagnostics. Within UGSF, the team “Regulation of molecular and cellular mechanisms by O-GlcNAcylation » led by Pr. Tony Lefebvre, pioneers research on O-GlcNAcylation’s regulation of chromatin dynamics, cancer metabolism, chemoresistance, and glycosylation control. Using CRISPR models, live-cell imaging, and glycoproteomics, they explore glyco-epigenetics and cancer biology at the cutting edge.

Nagoya University, one of Japan’s premier institutions, is internationally recognized for biomedical sciences, genome research, and precision medicine. Prof. Hiroshi Suzuki’s Laboratory of Molecular Oncology investigates gene regulation in cancer, focusing on the interplay between genome, epigenome, transcription, and RNA biology. Their integrative use of next-generation sequencing, computational biology, and genome/RNA engineering dissects super-enhancers, non-coding RNAs, and transcriptional pausing, identifying novel cancer therapeutic targets.

PLBS (Plateformes Lilloises en Biologie Santé) and iGCORE provide essential access to advanced technologies and expert support in genomics, glycomics, proteomics, bioinformatics, cellular and in vivo imaging, and high-throughput screening. PLBS, supported by five major institutions, unites 24 research units and over 150 technical specialists, ensuring comprehensive assistance from experimental design to data analysis. iGCORE, jointly established by Gifu University and Nagoya University, is a global glycoscience hub promoting international research collaboration, connecting with leading institutions worldwide to foster interdisciplinary innovation in glycobiology.

• Master’s degree in molecular biology, biochemistry, bioinformatics, or a related field
• Strong skills in molecular biology (cloning, CRISPR/Cas9, iPSC/organoid culture)
• Experience with omics technologies (RNA-seq, Hi-C, Cut&Tag, ChIP-seq, deep sequencing)
• Basic bioinformatics proficiency (R, Python)
• Fluent English, both written and spoken
• Motivated for interdisciplinary, international research