Individual
DC projects
Research project
The impact of nuclear NAD levels on transcriptional regulation and DNA repair
Rationale and objectives:
Nuclear NAD-dependent enzymes (PARPs1/2, SIRT1, 6, 7) control gene expression and DNA repair and produce the ligand of the macroH2A1.1 histone variants. Modulation of nuclear NAD levels could therefore represent an efficient means to regulate key nuclear processes.
Therefore, we plan:
• To establish technologies for the measurement and modulation of nuclear NAD levels using pharmacological and genetic approaches.
• To develop and implement techniques to determine nuclear NAD turnover using stable isotope labeling and mass spectrometry.
• To establish the impact of altered nuclear NAD availability on nuclear processes, and the extent of their NAD demand.
Expected results: Based on extensive experience from other cell organelles, we will generate unique genetically engineered
Envisioned Secondments
IJC (Buschbeck) months 22-25 (4 months) to learn methods to quantitatively analyse transcription and nuclear ADPribose sensing in the context of NAD modulations.
Recruitment
The estimated annual gross salary for the fellow will be €45.000 (approx.).