# Regulation of Protein Synthesis by Synonymous Codon Usage

> **NIH NIH R35** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $411,225

## Abstract

Summary
Biosynthesis of proteins accounts for 30% or more of the nutrients and energy consumed by proliferating cells,
and it is often dysregulated in human diseases such as cancer and neurological disorders. My research
program aims to develop an experimentally-constrained, biophysical model for protein synthesis at the whole-
cell level with the goal of predicting protein levels in normal and diseased cellular states. Our current focus is
on deciphering the kinetics of ribosome motion on mRNAs and its effect on protein expression. This research
builds on our recent discovery that synonymous codon usage is a potent determinant of ribosome kinetics and
protein abundance during nutrient-limited growth of bacteria. Notably, our experimental observations are not
explained by known hierarchies of codon usage bias or tRNA abundance. Our current results suggest that
biased usage of specific codons can regulate protein expression across several domains of life from microbes
to mammalian cells during fluctuations in nutrient availability. Our research strategy aims to establish the
mechanism and gene targets for this previously unsuspected, synonymous codon dependent
regulation of protein expression in bacteria and mammalian cells. Successful completion of this research
will provide a molecular basis for understanding the consequences of several hundred synonymous mutations
that have been recently implicated as drivers of cancer. In the longer term, the novel quantitative methods
developed in our research program will provide a rigorous modeling framework for deriving experimentally-
testable predictions from increasingly complex datasets such as ribosome occupancy measurements.

## Key facts

- **NIH application ID:** 9939573
- **Project number:** 5R35GM119835-05
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Arvind Rasi Subramaniam
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $411,225
- **Award type:** 5
- **Project period:** 2016-09-09 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939573

## Citation

> US National Institutes of Health, RePORTER application 9939573, Regulation of Protein Synthesis by Synonymous Codon Usage (5R35GM119835-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939573. Licensed CC0.

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