The Tse-Dinh Lab



1. Discovery of novel antibacterial lead compounds targeting bacterial topoisomerase I

Leads for novel antibiotics are urgently needed to combat bacterial pathogens resistant to current treatment. Enzyme based and cell based high throughput screening (HTS) assays are being developed and utilized to identify inhibitors that can act on bacterial topoisomerase I as mode of action. Hit compounds from HTS are being analyzed for SAR.

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2. Topoisomerase I Physiological Function and Regulation

The role of bacterial topoisomerase I in stress response and adaptation is being studied by genetics experiments. Protein-protein interactions direct topoisomerase function to relevant macromolecular complexes in cells. Bacterial topoisomerase I function is regulated by promoters utilizing multiple sigma factors. Other dynamic mechanisms of regulation of topoisomerase function and implications on the global system are being investigated.


3. Biophysical and Computational Studies of Topoisomerase Structure, Mechanism and Interactions

Structure, mechanism and interactions of E. coli and Mycobacterium topoisomerase I are being studied with biochemical, biophysical and computational approaches in our lab and through collaborations.

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