# Dynamics of Translation

> **NIH NIH R35** · STANFORD UNIVERSITY · 2023 · $766,987

## Abstract

PROJECT SUMMARY (30 lines)
Translation is the endpoint of the central dogma and point of temporal and spatial regulation in
gene expression. Biochemical, biophysical and structural methods have outlined the general
steps of translation, providing a menu of key factors, structures of ribosomes and complexes,
and kinetics for the essential steps of initiation, elongation and termination/recycling.
Nonetheless, the mechanisms of key steps such as initiation, elongation and termination, and
how they are regulated by RNA structures, modification or regulatory proteins remains unclear.
A key challenge is that translation is highly dynamic, involving conformational and compositional
changes throughout and following heterogeneous mechanistic pathways. During prior funding
periods supported by the grants that we will merge in this MIRA, we have developed single-
molecule approaches and reagents that observe translation in real time. We combine these
dynamic methods with cryoEM structures to gain a temporal and detailed mechanistic view of
the process. Our proposed research focuses on key areas translational control: how initiation is
achieved in higher organisms—here the pathway by which a small (40S) ribosomal subunit is
bound to a mRNA and recognizes a start—will be determined in both yeast and humans, and
we will explore how mRNA structure, protein binding and modified nucleotides change the
process. We will investigate how long-range RNA interaction between 5’ and 3’ ends of mRNAs
may be critical for basal translation initiation and its control. In elongation, we will continue to
explore recoding events and co-translational protein folding and develop methods to watch
translation elongation in eukaryotic organisms. We will explore the role of ribosomal
stalling/pausing and eventual shunting into ribosomal quality control pathways. Finally, we will
understand the pathways by which correct stop codons are recognized and ribosomes recycled
and determine how correct vs premature stop codons are distinguished in the nonsense
mediated decay pathway. Our research leverages decades of reagent and methods
development, and a wonderful group of collaborators to explore translational control, and its
central linkage to human health and disease.

## Key facts

- **NIH application ID:** 10617792
- **Project number:** 5R35GM145306-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JOSEPH D PUGLISI
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $766,987
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617792

## Citation

> US National Institutes of Health, RePORTER application 10617792, Dynamics of Translation (5R35GM145306-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10617792. Licensed CC0.

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