# The adaptive potential of translational regulation

> **NIH NIH F32** · NEW YORK UNIVERSITY · 2021 · $17,141

## Abstract

Project Summary/Abstract
 Our current understanding of the adaptive effects of mutation is largely limited to
alterations in protein coding sequence and disruption of transcriptional cis-regulatory
promoters. Very little is known about how mutations alter translation, or the role these
mutations play in adaptation and evolution. This project seeks to address this gap by
identifying the functional effect of mutations on translation. To accomplish this I will first
identify mutations that arise from adaptation to various nutrient limited environments. I will
then use expression profiling (e.g. RNA-seq, ribosome profiling, and RATE-seq) to identify the
effect these mutations have on translation, as well as other levels of gene expression. This will
provide insight into the magnitude of effect mutations have on translation and their relative
rate. Furthermore, to fully characterize the role synonymous mutations have on fitness I will be
using a deep scanning synonymous mutation library. To understand the role tRNA abundance
plays in the fitness effect of a given synonymous mutations, I will also be evaluating fitness
within tRNA under- and over-expression backgrounds. Because of the closely coupled nature of
translation rates and mRNA decay, I will also characterize the effect synonymous mutations
have on mRNA decay using RATE-seq. My analysis of the functional effects of these mutations
on gene expression, particularly within the genetic background and environment in which they
arose, will allow for the development of a machine learning algorithm that can use sequence
and annotation features to predict the effect of a mutation on gene expression. This tool will aid
future research into the effect mutations have of gene expression by allowing the identification
of high-confidence candidates for further evaluation.
 This project will be conducted at New York University’s Center for Genomics and
Systems Biology, whose mission is to answer otherwise intractable biological questions using
applied experimental and computational approaches. The Center houses numerous facilities
and cores that will be instrumental in the performance of this work. The collaborative
atmosphere and multi-disciplinary nature of NYU’s research communities that will enable me
to stay abreast of developments in related fields and to rapidly communicate my research to
interested parties. I will be trained under the guidance of Dr. David Gresham, an excellent
researcher working on complementing long-term evolution experiments with gene expression
studies to characterize the adaptive potential of the regulation of gene expression.

## Key facts

- **NIH application ID:** 10336339
- **Project number:** 5F32GM131573-03
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Pieter Spealman
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $17,141
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10336339

## Citation

> US National Institutes of Health, RePORTER application 10336339, The adaptive potential of translational regulation (5F32GM131573-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10336339. Licensed CC0.

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