# Bacterial ribosome heterogeneity and gene expression

> **NIH NIH R35** · UNIVERSITY OF LOUISVILLE · 2024 · $399,584

## Abstract

PROJECT SUMMARY
 As antibiotic resistance increases globally, there is an urgent need for new drugs to
combat bacterial infections. Approaches to developing new antimicrobials include inhibiting
essential steps in gene expression and inhibiting virulence factor production. The overarching
focus of the research program in my laboratory is to understand how bacterial cells
regulate gene expression, to ultimately identify novel targets for antimicrobial
development. The research funded by this award will leverage the Ramsey laboratory’s
expertise in bacterial genetics and state of the art technologies to examine the impacts of
ribosome heterogeneity in multiple bacterial species. The Ramsey laboratory identified a
specific homolog of the ribosomal protein bS21 that governs virulence gene expression in a
bacterial pathogen. These findings suggest that heterogeneity in ribosomes, which are significant
drug targets, can lead to changes in gene expression. The impacts of ribosome heterogeneity on
translation, gene expression, and drug efficacy are generally not well understood and represent
key gaps in our knowledge. Over the next five years, we propose to continue our studies to
understand the effects of ribosome heterogeneity on multiple bacterial species. The proposed
work is innovative because it takes a rigorous, reductionist approach to examine one poorly-
understood source of ribosome heterogeneity with species-specific impacts on translation to
elucidate fundamental features of translation and inform the design of novel antimicrobials. Our
goals include determining how multiple bS21 homologs function to govern gene expression, why
bS21 is essential in some cells, and how bS21 contributes to antibiotic sensitivity. We expect our
work will allow us to make clear connections between ribosome composition and functional
outcomes, as we will limit the complexity of ribosomal heterogeneity to changes in a single
ribosomal protein, bS21. Expected future work will include developing screens for novel, specific
ribosome inhibitors and studying the function of bS21 or other independent sources of ribosome
heterogeneity in these and/or other organisms. Ultimately our studies will provide key insights into
ribosome function, gene expression, and may identify novel targets for antimicrobial drugs.

## Key facts

- **NIH application ID:** 11248163
- **Project number:** 7R35GM150599-03
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Kathryn Mary Ramsey
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,584
- **Award type:** 7
- **Project period:** 2023-08-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11248163

## Citation

> US National Institutes of Health, RePORTER application 11248163, Bacterial ribosome heterogeneity and gene expression (7R35GM150599-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11248163. Licensed CC0.

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