# Cross-kingdom health: evolution of innate immune receptors and their targets

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $1,306,037

## Abstract

PROJECT SUMMARY
Innate immune receptors from the NLR protein family control basic organism-organism interactions across
kingdoms, including incompatibility within a species. Current availability of genomic biodiversity allows
us to examine patterns of innate immune receptor evolution. I propose that adaptive immunity has evolved
by adopting subsets of proteins domains already present in innate immunity as well as their diversification
mechanisms to act somatically in specialized cells. Testing this hypothesis through comparative genomics
will be paradigm-shifting to our understanding of immune system evolution. To do this, we will examine
evolution of protein domains involved in innate immunity across all available eukaryotic genomes,
determine sources of genomic diversity and how they change with the re-current evolution of adaptive
immunity across independent lineages. To test that there are targeted diversity generation mechanisms
acting on NLRs at the population level, we will examine patterns of NLR evolution on multiple scales,
including cross-kingdom analyses. We will test diversification mechanisms acting on them within species
lacking adaptive immunity, including model plants and fungi. In parallel, we will experimentally test
involvement of NLRs in fungal immunity, which has been proposed but yet to be experimentally validated.
Finally, we will conduct experimental evolution on both NLRs and their ligands to collect data for modeling
how new binding specificities arise on the population scale. Altogether, this project will fill in important
gaps in understanding the evolution of innate immune systems, including our own.

## Key facts

- **NIH application ID:** 10244753
- **Project number:** 1DP2AT011967-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Ksenia V Krasileva
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,306,037
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244753

## Citation

> US National Institutes of Health, RePORTER application 10244753, Cross-kingdom health: evolution of innate immune receptors and their targets (1DP2AT011967-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10244753. Licensed CC0.

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