# Dynamics and evolution of translational regulation

> **NIH NIH R35** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $381,022

## Abstract

Project Summary
Translating information from DNA to proteins is the most energetically expensive process a cell
undertakes. The basic principles of translation are simple — free-floating ribosomes bind to
mRNAs and translate the transcript one codon at a time, each of which is recognized by a
corresponding tRNA. In recent years, our understanding of the molecular basis of translation has
improved significantly. Advances in structural biology have provided a detailed view of how an
individual ribosome rests at a particular codon on an mRNA, recognizes a tRNA, makes peptide
bonds, and then physically translocates to the next codon. Many factors, such as patterns of
codon usage, mRNA structures, transcript abundances, protein domain-architectures, lengths of
genes and untranslated regions (UTRs), and initiation and elongation rates have all been shown
to modulate protein production. However, there exist two critical gaps in our understanding of
dynamics and evolution of translation. First, we lack a coherent view of how all the various factors
involved in translation interact with each other to regulate the global pace of protein synthesis in
a cell. Second, we know little about how regulation of protein synthesis changes over time during
organismal evolution and speciation. To address these critical gaps, we will develop a synthetic
modeling framework for transcription and translation, and parameterize it by generating high-
throughput genomic datasets. We will employ this combined modeling/experimental approach to
study the dynamics and regulation of protein synthesis in a panel of model organisms and evolving
populations. In the long-term, this hybrid approach will allow us to study how a cell modulates
translation in different contexts, including viral infections and systemic diseases such as cancer.
This framework will be particularly useful for elucidating the mechanisms of diseases that arise
from synonymous mutations leading to opportunities for development of therapeutic interventions
to modify protein synthesis in a targeted manner.

## Key facts

- **NIH application ID:** 9999616
- **Project number:** 5R35GM124976-04
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Premal R Shah
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,022
- **Award type:** 5
- **Project period:** 2017-09-14 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999616

## Citation

> US National Institutes of Health, RePORTER application 9999616, Dynamics and evolution of translational regulation (5R35GM124976-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999616. Licensed CC0.

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