# The origins and evolution of eukaryotic antibacterial defenses

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $376,200

## Abstract

PROJECT SUMMARY
 Molecular mechanisms of innate immunity are constantly changing as organisms evolve to defend
against the threats of newly emerged pathogens. As a consequence, our innate immune pathways are a
patchwork of both ancient and recently evolved proteins. How did mechanisms of innate immunity arise, and
how have these pathways adapted to integrate new defenses? The answers to these questions are important
because these dynamics have shaped the functions of modern-day immunity, determining how hosts are
protected from infectious diseases. Moreover, because immune pathways are evolutionarily flexible, they can
serve as an excellent model for how cellular signaling networks assemble and diversify more broadly.
 We focus on the evolution of cell-autonomous immunity, which provides critical protections within
infected cells. Aspects of cell-autonomous immunity are found across eukaryotes, including in unicellular
phagocytic organisms that interact with bacteria in natural environments. To understand how ancient immune
proteins have assembled into modern mammalian pathways, we use diverse eukaryotes at ideal
phylogenetic positions to uncover the origins and evolution of innate immunity. We use the highly
tractable Dictyostelium system to discover and characterize antibacterial defenses in amoebae, while
leveraging additional eukaryotes to understand how immune proteins and pathways have evolved. Our
experiments integrate molecular, biochemical, genetic, cellular, evolutionary, and genomic approaches to
reveal genes functionally important for defending against bacterial infections in diverse organisms. Because
cell-autonomous defenses are easier to observe and study in haploid, unicellular species, these experiments
promise to uncover new mechanisms of cell-autonomous immunity. Some of these mechanisms may be
deeply conserved with immune defenses in animals, allowing us to reconstruct how these immune pathways
arise and change. Other immune mechanisms in these diverged eukaryotes may represent novel evolutionary
solutions to the problem of cellular defense, yielding both practical molecular tools such as new antimicrobials
and novel paradigms of immunity.

## Key facts

- **NIH application ID:** 10893033
- **Project number:** 5R35GM150681-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Tera Catherine Levin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,200
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893033

## Citation

> US National Institutes of Health, RePORTER application 10893033, The origins and evolution of eukaryotic antibacterial defenses (5R35GM150681-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10893033. Licensed CC0.

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