The main research objective of Georges Mer, Ph.D., is to understand how post-translational modifications (PTMs) can regulate the formation of transient protein complexes and enzyme catalysis. His team approaches problems from a structural biology perspective and employs a range of complementary biochemical and biophysical techniques, including nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and cryo-electron microscopy (cryo-EM). Current studies in his laboratory concentrate on the DNA damage response and transcription, and the contribution of chromatin dynamics to these processes.
- Nucleosomal PTMs in the DNA damage response. Dr. Mer's team is interested in understanding how the concerted involvement of multiple PTMs (acetylation, ADP-ribosylation, methylation, phosphorylation and ubiquitylation) in the nucleosome or nucleosome arrays controls the assembly of DNA repair protein complexes at DNA damage sites and how PTMs can function as switches for protein activation or inactivation.
- Structure and function of histone chaperones. Histone chaperones contribute to the remodeling of chromatin during the DNA damage response, DNA replication and gene transcription. Dr. Mer's team studies how PTMs in histones regulate the association of histones with chaperones and how chaperones can alter the function of histone modifying enzymes.
- Protein dynamics. Related to the above projects, Dr. Mer and colleagues use NMR spectroscopy, small-angle X-ray scattering and calorimetry to probe how protein flexibility contributes to the specificity of molecular recognition.
Significance to patient care
The research of Dr. Mer and his team has relevance to a better understanding of cancer and neurological disorders. Their basic mechanistic studies may, in the long term, facilitate the development of new therapeutics for cancer treatment.