Beyond chromatin regulation, TIP60-C acts as a central signaling hub that coordinates diverse cellular processes, including DNA repair, immune responses, cell cycle progression, apoptosis, autophagy, metabolism, and development. These functions are mediated through the acetylation of both histone and non-histone substrates, which modulates protein activity, stability, and molecular interactions. Dysregulation of TIP60-C is implicated in numerous human diseases, including cancer, neurodegenerative disorders, and viral infections, making it a compelling therapeutic target.
Our laboratory recently solved the high-resolution cryo-EM structure of the endogenous human TIP60 complex (https://www.nature.com/articles/s41586-024-08011-w), providing an unprecedented view of its molecular architecture. This PhD position builds directly on that breakthrough.
Project Aims
- Determine how TIP60-C recognizes nucleosomes to drive H2A.Z exchange.
- Elucidate the molecular mechanisms by which TIP60-C promotes DNA damage repair.
- Identify and develop novel therapeutic modulators of TIP60-C.
Approach
The project integrates structural biology, biochemistry, cell biology, and computational drug discovery. The successful candidate will employ an interdisciplinary approach, combining single-particle cryo-electron microscopy, structure-based virtual screening, AI-driven de novo peptide and mini-protein design, biochemical characterization, and cellular functional assays.
Candidate Profile
- Highly motivated, with a strong interest in structural biology and biochemistry
- Master's degree (or near completion) in biochemistry, chemistry, molecular biology, biomedical sciences, or a related field.
- Prior experience in protein biochemistry, structural biology, computational biology, or cell biology is a plus, but not required.
- Strong communication skills, intellectual curiosity, and the ability to thrive in a collaborative, international research environment.
Expected start date: 1 December 2026.
What We Offer
- Access to state-of-the-art cryo-EM facilities and cutting-edge computational infrastructure.
- Membership in a dynamic, international team at IGBMC working at the interface of structural biology and structure-based drug leads design.
- A three years’ contract (fourth-year extension possible, subject to competitive funding), salary approximately €2,300 gross/month.
Application
Interested candidates should send a CV, a brief statement of research interests, Grades obtained during the Licence and Master studies, and contact details for two references to lic@igbmc.fr before 30 September, 2026.
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