Summary
This research project aims to uncover the individual molecular mechanisms of ATP-dependent chromatin remodelers and Sirtuin histone deacetylases, and their coordinated roles in regulating nucleosome dynamics and chromatin structure.
Molecular Mechanisms of Chromatin Remodeling and Deacetylation
US · IL
NIH
grant
awarded
#nih-1R35GM161751-01
What they want
The research is divided into two major themes. The first theme investigates ATP-dependent chromatin remodelers, specifically CHD and ISWI ATPases, focusing on their catalytic mechanisms, substrate specificity, and the impact of histone post-translational modifications (PTMs) on their remodeling activity. The second theme examines the Sirtuin family of deacetylases and their interplay with chromatin remodelers, utilizing structural and functional studies.
Deliverables
- Reveal the dynamics of remodeling cycles and interactions with chromatin
- Provide unprecedented insights into the coordination and regulatory roles of Sirtuins and chromatin remodelers
- Advance understanding of chromatin modulation
- Offer critical insights into gene regulation, genome integrity, and therapeutic strategies for diseases like cancer and neurodegeneration
Technical requirements
- High-resolution cryo-electron microscopy (cryo-EM)
- Molecular dynamics simulations
- Advanced biochemical assays
- Synthetic nucleosomes with defined PTMs
- Real-time FRET-based translocation assays
- Cross-linking mass spectrometry
