# Imaging Protein Synthesis on the Ribosome using Single-Molecule FRET

> **NIH GM R35** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2026 · $678,370

## Abstract

PROJECT ABSTRACT:
The mechanism and regulation of protein synthesis determines the diversity and capacity of the cellular
proteome. At the center of this regulation is the ribosome - a megadalton RNA-protein complex composed of
two-subunits – which integrates a wide variety of cellular signals. The ribosome’s exquisite sensitivity to
regulatory cues is underscored by the fact that the majority of clinically used antibiotics exert their effect by either
dysregulating or blocking specific aspects of the protein synthesis mechanism. Understanding the kinetic and
structural basis of protein synthesis promises to elucidate core paradigms of gene expression control and to
inform strategies for addressing the global threat posed by drug-resistant and emerging pathogens. Moreover,
given that loss of translational control is a hallmark of cancer, a mechanistic understanding of ribosome function
holds significant promise for developing novel small-molecule therapies, which are currently lacking in the
treatment of human disease. Historically, investigations into structure-function relationships governing the
protein synthesis mechanism have focused on bacterial systems approaches. Comparable studies in human
systems have been hindered by the demand for large amounts of homogeneous protein synthesis machinery.
As a result, the molecular distinctions between bacterial and mammalian protein synthesis - which underpin
antibiotic specificity and potential therapeutic windows – remain obscure. Current evidence suggests that the
elongation phase of protein synthesis, during which messenger RNA (mRNA) is decoded into protein, is the most
time consuming, physiologically regulated and small-molecule sensitive. We and others hypothesize that
elongation is particularly susceptible to regulation because it involves transient, repetitive interactions of the
ribosome with auxiliary factors, coordinated through finely tuned conformational transitions that are acutely
sensitive to perturbatio

## Key facts

- **NIH application ID:** 11331580
- **Project number:** 1R35GM163846-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Scott C Blanchard
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $678,370
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2031-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11331580

## Citation

> US National Institutes of Health, RePORTER application 11331580, Imaging Protein Synthesis on the Ribosome using Single-Molecule FRET (1R35GM163846-01). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11331580. Licensed CC0.

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