# Evolutionary innovations from host-microbe interactions

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $221,189

## Abstract

PROJECT SUMMARY
The genomes of microbes and their hosts are intertwined through time. Pathogenic microbes
evolve mechanisms to manipulate host cell functions and hosts evolve mechanisms defending
from infections. Buried in this evolutionary history of host-microbial conflict are genetically
encoded innovations conferring pivotal advantages. Sometimes the discovery of these functions
presents an opportunity to harness the process as a research tool. Antibodies, restriction
endonucleases, and CRISPR/Cas systems are examples of natural immune processes
repurposed to revolutionize modern biology. A central premise of this proposal is to take a
similar view of host-microbe conflict as a crucible for biological innovation. Our approach guides
rigorous multidisciplinary studies using complementary computational and experimental analysis
to investigate diverse host and microbe processes. Our work is revealing a new class of broadly
acting antiviral functions. By considering the evolutionary implications of enveloped viruses
exploiting the endosomal sorting complex required for transport (ESCRT) pathway, we
discovered a new host immune function, encoded by retroCHMP3, that can block the release of
maturing virus particles from infected cells. In addition to characterizing the evolutionary process
leading to this specific biological innovation, we will develop new computational pipelines to
discover related antimicrobial functions in genomes of diverse mammals. The work is also
revealing a primary role for retrotransposons and other selfish genetic elements in creating and
regulating genes involved in host-virus conflicts. New discoveries related to the activity of selfish
genes also applies to our work on DNA virus evolution. Using vaccinia virus as a model system
for large DNA virus evolution, we are pursuing several experimental schemes revealing
mechanisms of virus adaptation. One example tackles the question of how viruses acquire host
genes through horizontal transfer, a mechanism of adaptation common in diverse virus classes.
Discovering a primary role for retrotransposons in mobilizing host transcripts to virus genomes
connects classic work on phage transduction in bacteria with eukaryotic systems and opens a
range of new questions related to virus control of genetic exchange among diverse species.
Finally, we will extend our studies to host systems outside dedicated immune defenses,
including a project studying intriguing signals of rapid evolution in proteins regulating water
balance in the intestine. These genetic conflicts involve enteric pathogens causing diarrhea and
guide new studies aimed at repurposing host peptide variants as novel antibiotic strategies.

## Key facts

- **NIH application ID:** 9851670
- **Project number:** 1R35GM134936-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Nels C. Elde
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $221,189
- **Award type:** 1
- **Project period:** 2020-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851670

## Citation

> US National Institutes of Health, RePORTER application 9851670, Evolutionary innovations from host-microbe interactions (1R35GM134936-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851670. Licensed CC0.

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