# Genome exploration through toxin-mediated ribosome stalling

> **NIH NIH R01** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2021 · $379,916

## Abstract

Project Summary
Approximately 90% of individuals infected with Mycobacterium tuberculosis (Mtb) develop an asymptomatic
latent infection, which is non-infectious. Although some individuals may eradicate this infection, those who do
not comprise a large reservoir of persons who can convert from latent to active TB, which is infectious.
Reactivation is especially likely in immune-compromised individuals, including those infected with HIV. The
molecular switches that enable Mtb to slow or stop replication, become dormant and establish latent TB infection
are poorly characterized. A thorough understanding of these switches is critical for development of 1) diagnostics
to enable prediction of reactivation risk and 2) shorter, more effective treatment regimens for latent TB infection.
Toxin-antitoxin (TA) systems are strongly implicated in establishment of latent TB infection because their toxin
components typically downregulate Mtb cell growth and are activated in response to stresses relevant to this
state. Yet, the extraordinary redundancy of TA systems make determination of the individual contributions of
each toxin challenging using conventional genetic and molecular biological approaches. We propose to use a
powerful battery of genome-scale tools to track the fate of transcripts, ribosomes and proteins in response to
activation of a subset of tRNA-cleaving toxins to understand the molecular mechanisms that underlie stress
survival. We then exploit our finding that the codon-specific ribosome-stalling characteristic of these toxins
identifies novel ORFs and apply this as a reliable tool for improved Mtb genome annotation.

## Key facts

- **NIH application ID:** 10159845
- **Project number:** 5R01AI154464-02
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** NANCY ANN WOYCHIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,916
- **Award type:** 5
- **Project period:** 2020-05-07 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159845

## Citation

> US National Institutes of Health, RePORTER application 10159845, Genome exploration through toxin-mediated ribosome stalling (5R01AI154464-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159845. Licensed CC0.

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