The main research goal of Georges Mer, Ph.D., is to understand how post-translational modifications (PTMs) regulate the formation of transient protein complexes and enzyme catalysis, with a focus on DNA damage signaling and repair. 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 to probe the structure and dynamics of macromolecules. Current studies in his laboratory concentrate on the mechanisms of action of several DNA double-strand break repair proteins, including 53BP1 and BRCA1-BARD1, and on understanding the contribution of chromatin dynamics to the DNA damage response.
- 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 participate in chromatin remodeling 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, calorimetry and other biophysical approaches to probe how protein flexibility contributes to the specificity of molecular recognition and enzymatic catalysis.
Significance to patient care
Investigations in Dr. Mer's laboratory have relevance to a better understanding of cancer and neurological disorders. This team's focus on basic mechanistic studies may, in the long term, facilitate the development of new therapeutics for cancer treatment.