# Ribosome Quality Control Mechanisms in Gram-positive Bacteria

> **NIH NIH R35** · CORNELL UNIVERSITY · 2022 · $367,640

## Abstract

Project Summary:
Although bacterial ribosomes have been biochemically interrogated for decades, unknown mechanisms of
regulation and quality control are regularly uncovered and targeted with new antibiotics. Major differences in
translation regulation between Gram-positive and Gram-negative bacteria have come to light in recent years.
Although more than 200,000 infections per year in the United States are caused by antibiotic resistant Gram-
positive bacteria, major gaps remain in our understanding of how Gram-positives perform ribosome quality
control. To address these gaps, my research program will focus on two major areas. 1) We will identify and
characterize strategies used by Gram-positive bacteria to detect and rescue stalled ribosomes and investigate
the physiological impacts of ribosome stalling. Preliminary data from my laboratory supports a model in which
ribosome stalling in Bacillus subtilis and Bacillus anthracis results in frameshifting and premature translation
termination. This process is expected to result in toxic truncated proteins and trigger stress responses. We will
investigate this model using genetic, structural, and biochemical approaches. 2) We will determine how ribosome
flexibility and atypical translation events can be used by the cell to increase coding capacity. We are particularly
interested in how frameshifting and stop codon read-through regulates gene expression and how environmental
inputs control this type of regulation. We will also use unbiased high throughput genetics to uncover new
mechanisms that prevent stalling and that regulate programmed frameshifting and stop codon read-through.

## Key facts

- **NIH application ID:** 10499046
- **Project number:** 1R35GM147049-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Heather Feaga
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,640
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499046

## Citation

> US National Institutes of Health, RePORTER application 10499046, Ribosome Quality Control Mechanisms in Gram-positive Bacteria (1R35GM147049-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10499046. Licensed CC0.

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