This $900,000 Project Grant award from the National Science Foundation (NSF) Biological Sciences program (CFDA 47.074) to North Carolina State University (NC State) is for a collaborative research project to unravel the mechanisms underlying DNA mismatch repair systems and their role in causing simple sequence repeat (SSR) expansions that lead to over fifty neurological and neuromuscular diseases.
The project combines single-molecule fluorescence resonance energy transfer (smFRET) experiments and atomistic molecular dynamics (MD) simulations to elucidate the structural, mechanistic, and dynamical aspects of nucleotide and mismatch repair (MMR) complexes, as well as the role of atypical nucleic acid structures like DNA three-way junctions and R-loops in SSR expansions. The research aims to map potential dynamical pathways for R-loop generation and understand how the DNA MMR system interacts with SSR DNA, with the ultimate goal of uncovering the underlying mechanisms of SSR expansion. In addition to the scientific impact, the project will train several students and support the continued development and distribution of the AMBER molecular simulation software.
Generated 3/4/25, 2:36 AM