The Liu lab is working to address the problem of drug-resistant Mycobacterium tuberculosis (Mtb) by combining a novel RNA-sequencing method to map full-length sequences of all RNA transcripts in Mtb with the use of a single-molecule platform to visualize the dynamic behavior of individual Mtb RNA polymerases (RNAPs) and their interplay with regulatory factors, depicting the entire Mtb transcription cycle with high spatiotemporal resolution. A better understanding of the mechanism and regulation of Mtb transcription is critical to the development of new therapeutic strategies because RNAP mutations underlie drug resistance.
Faithful inheritance and precise expression of genetic information are carried out by specialized macromolecular machines. These nanometer-scale entities must negotiate the physical characteristics of DNA and chromatin in order to fulfill their function. Leveraging the single-molecule biophysical toolkit, Liu investigates the molecular underpinnings of interaction, coordination, and competition of machines that act on bacterial and eukaryotic chromosomes.
