Time-resolved mechanisms of essential biological pathways.

Abstract

The diversity of enzyme structure and function in living systems leads to exciting opportunities in biophysical research. Large numbers of these protein machines coordinate across space and time and undergo drastic changes in shape to carry out complex biological processes. My lab focuses on investigating precisely how genetic mutations impact the molecular function of key enzymes involved in DNA repair and/or RNA processing pathways. We use single molecule time-resolved fluorescence spectroscopy as a tool to explore in real time the protein-nucleic acid interactions and dynamic structural rearrangements that drive specific pathways. We are currently studying the detailed mechanisms SARS-CoV-2 viral RNA processing, ribosome assembly, and DNA mismatch repair. I will present recent results from pulsed interleaved excitation fluorescence resonance energy transfer (PIE-FRET) and fluorescence correlation spectroscopy (FCS) experiments. We aim to completely characterize the impact of mutations linked to disease on the molecular function of enzymes to understand how complex diseases develop at the molecular level and to identify new therapeutic targets.