# Structural Robustness of Ribosome Functional Centers

> **NIH NIH R01** · BROWN UNIVERSITY · 2022 · $360,427

## Abstract

Project Summary
The ribosome is the macromolecular machine, conserved throughout evolution, that is
responsible for the synthesis of proteins and is therefore a fundamental component of gene
expression. Because of its central role in biochemistry, the ribosome has become the target of
more than half of all antibiotics, and the evolution of antibiotic resistance due to mutations in the
ribosome has become a major threat to human health. Understanding the molecular basis of
antibiotic resistance therefore has significant implications for the fight against the threat of
resistance. In deciphering the mechanism of antibiotic resistance, fundamental insights into the
mechanism of ribosome function can also be acquired, leading to possible novel antimicrobial
agents through rational drug design. Through an ongoing collaborative effort, this proposal
capitalizes on the ability of the PIs to combine genetics and structural biology to address
fundamental questions of ribosome structure and function and provide a framework for future
development of novel antimicrobial agents. The Aims of this proposal are: (1) Dissect 30S subunit
conformational dynamics during tRNA movement through the ribosome; (2) Define the role of two
intersubunit bridges in 30S-50S rotation during translocation; (3) Determine the structural basis
for signaling pathways through the ribosome.
 Achieving these aims will involve exploiting the expertise of the three PIs to generate and
characterize functionally impactful mutants and determine their structures by X-ray
crystallography or cryo-electron microscopy. The strengths of our proposal include: (1) extensive
expertise in the experimental methods to be applied; (2) a long track record of effective
collaboration between the PIs; (3) an extensive publication track record in the field of ribosome
structure and function; (4) a large volume of preliminary data and ongoing studies, including
multiple studies nearing completion. Accomplishing these goals will significantly advance the field
by answering long-standing questions about antibiotic resistance mechanisms, while
simultaneously expanding our understanding of the basic underlying mechanism of the ribosome.

## Key facts

- **NIH application ID:** 10478082
- **Project number:** 5R01GM094157-11
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Steven Thomas Gregory
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $360,427
- **Award type:** 5
- **Project period:** 2010-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478082

## Citation

> US National Institutes of Health, RePORTER application 10478082, Structural Robustness of Ribosome Functional Centers (5R01GM094157-11). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10478082. Licensed CC0.

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