National Institute of General Medical Sciences 1R35GM166110-01

Exploring RNA Polymerase Dynamics and Regulatory Architecture Across Divergent Bacterial Species

The project investigates bacterial RNA polymerase transcription mechanisms across species to develop species-specific inhibitors and antimicrobial strategies, using advanced sequencing and molecular techniques.

Description

This research project aims to study how the mechanisms of transcription and its regulation differ across bacterial species and to exploit these differences for species-specific RNA polymerase inhibitors as research tools and antimicrobial leads. The study uses a sequencing platform to map pause and termination sites of RNA polymerase at single-nucleotide resolution across various bacterial species, combining cryo-EM, biochemical assays, deep learning, and bacterial genetics. Key findings include identification of premature termination events in 5' untranslated regions associated with stable RNA secondary structures and insights into their regulatory roles, providing fundamental principles of transcription and opportunities for antibiotic development.

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