# Administrative Equipment Supplement for Regulation and function of bacterial 100S ribosome

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $59,072

## Abstract

PROJECT SUMMARY (from the parental award)
 During bacterial protein synthesis, the 30S and 50S ribosomal subunits assemble into the
translationally active 70S ribosome on template mRNA. In the Gram-positive human bacterial
pathogen Staphylococcus aureus, a single small ribosome-binding protein called hibernation-
promoting factor (SaHPF) stimulates the dimerization of 2.5-MDa 70S monomers to form the
translationally silent 100S complex. The physiological function of the 100S ribosome remains
enigmatic because the temporal abundance of the 100S ribosome varies considerably among
different bacterial phyla, the global impact of the 100S ribosome on translation is completely
unknown, and hpf null mutants of different bacteria lack a common phenotype. Moreover, distantly
related gammaproteobacteria, such as E. coli, require two proteins (EcRMF and EcHPF) to
achieve 100S complex formation. Recent data from our group demonstrate that SaHPF is
essential for the bacterial survival and maintenance of the ribosome pool in aging S. aureus cells.
Surprisingly, eliminating Sa_hpf causes the derepression of only a subset of genes at translational
initiation. Our goal is to establish a mechanistic understanding of the function of the 100S
ribosome in translational capacity and staphylococcal pathogenesis. We will take a multi-
disciplinary approach that spans genetics, molecular biophysics, biochemistry, and whole animal
infection studies. Aim 1 will determine the process and factors involved in the reversible
conversion of 70S and 100S ribosomes. Aim 2 will determine how the SaHPF/100S ribosome
inhibits translation in a gene-specific manner. Aim 3 will identify the roles of the 100S complex in
ribosome turnover and staphylococcal pathophysiology. These aims have the potential to produce
novel insights into ribosome metabolism and inspire alternate treatments for persistent and
relapsed staphylococcal infections that are intimately linked to survive for an extended period
inside the host.

## Key facts

- **NIH application ID:** 10582284
- **Project number:** 3R01GM121359-05S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** M.-N. Frances Yap
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $59,072
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10582284

## Citation

> US National Institutes of Health, RePORTER application 10582284, Administrative Equipment Supplement for Regulation and function of bacterial 100S ribosome (3R01GM121359-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10582284. Licensed CC0.

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