# Molecular basis of ionizing radiation resistance

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $293,280

## Abstract

Project Summary/Abstract
In this project, we will systematically define the genetic and cellular adaptations
associated with an extremophile phenotype in bacteria – extraordinary resistance
to the effects of ionizing radiation (IR). Instead of studying prototypical IR
resistant species such as Deinococcus radiodurans, we are generating IR resistant
Escherichia coli populations by directed evolution. The resulting strains approach,
and in some cases exceed the levels of IR resistance seen in Deinococcus. Analysis
of the mutations underlying the acquired phenotype will allow us to quickly
home in on the key cellular innovations. The ultimate goal is to define ALL
processes and mechanisms that contribute to an extreme IR resistance
phenotype. The directed evolution of this phenotype in E. coli provides a
window that makes this possible.
 In this work we will both exploit and expand an existing resource of four
highly evolved populations of E. coli. Using directed evolution, all of these have
acquired high levels of IR resistance. The populations are designated IR-1-20, IR-
2-20, IR-3-20, and IR-4-20. We have already defined the mutations most relevant
to the phenotype in both IR-2-20 and IR-3-20. In addition, we are currently
generating four new evolved populations from scratch, using a different type of
radiation source, and further evolving the four existing populations. There are
four specific aims:
 Aim 1 focuses on the evolution of new and existing populations, as well as
definition of the mutations that make substantial contributions to the phenotype.
Defined strains with key contributing mutations, isolated in an otherwise wild
type background, will be constructed. Aim 2 represents a general effort to use the
modern resources of systems biology to thoroughly characterize the evolved
populations and single colony isolates derived from them. Aim 3 will focus on an
exploration of one particular contributing mechanism of IR resistance involving
genetic alterations in genes encoding proteins involved in replication restart.
Aim 4 is the capstone. We will use information gained from aims 1-3 to transfer
the IR resistance phenotype intact by introducing a defined set of mutations into
Salmonella enterica.

## Key facts

- **NIH application ID:** 9923665
- **Project number:** 5R01GM112757-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Michael M. Cox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,280
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923665

## Citation

> US National Institutes of Health, RePORTER application 9923665, Molecular basis of ionizing radiation resistance (5R01GM112757-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9923665. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*