Single-molecule investigations of fast biomolecular search processes initiating DNA repair

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The overarching objective of my research program is to create a new mechanistic understanding of the fast molecular search processes, which underlie a host of key cellular processes. One class of fast molecular search processes, that remain largely uncharacterized due to limited analysis techniques, is the search that initiates the constant processes of DNA repair following its cleavage by ionizing radiation, free radicals and during replication. Existing microscopy techniques are not capable of characterizing these molecular searches under physiological conditions because they can not simultaneously resolve: weak protein-DNA and DNA-DNA interactions; extended search trajectories of individual molecules over several seconds, and millisecond-timescale interaction kinetics; nor are they compatible with topologically complex or strained DNA substrates. I will circumvent these limitations using a new suite of custom single-microscopy techniques which extend CLIC-imaging.