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Transcription
We have developed a single-molecule platform to visualize DNA transcription by individual RNA polymerases (RNAPs) over many kilobases. In the meantime, we have developed SEnd-seq, a sequencing method that simultaneously maps both 5’ and 3’ RNA ends in a transcriptome. These novel technologies enable us to gain unprecedented insights into the coordination between RNAPs and their regulatory factors on a crowded genome in both bacterial and eukaryotic systems.
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Replication
We have established a longstanding collaboration with the O’Donnell Lab to study the eukaryotic replisome, a multi-component macromolecular machine responsible for genome replication. Our approach—single-molecule observation combined with in vitro reconstitution—offers the best opportunity to dissect the intricate dynamics of individual constituents within this extraordinarily sophisticated machinery.
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Chromatin
Leveraging single-molecule manipulation and visualization, we have shown that nucleosomes are more than passive DNA packaging units of eukaryotic chromatin, but also potent hotspots to recruit DNA-binding proteins and DNA-processing machines and modulate their activities. As such, the physical parameters of the nucleosome constitute a rich layer of epigenetic regulation for genomic transactions.
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Miscellaneous
Besides our main interests in the central dogma and epigenetics, we have also collaborated widely with groups within and outside Rockefeller and applied our expertise in single-molecule techniques to other areas of biology ranging from membrane proteins to cytoskeleton, CRISPR-Cas and SARS-CoV-2.
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Single-molecule reviews
We have written several review articles to introduce the booming field of single-molecule biology, its mainstream methodology and latest applications, as well as our perspective on its future directions.