# A general test of the genetic basis of parasite resistance across genetic and environmental contexts

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2024 · $59,754

## Abstract

Project Summary
A priority in infectious disease research is to identify the genes that increase an individual’s resistance
to a given infection. Variation in resistance clearly has a strong genetic basis, making it seemingly an
ideal trait for identifying causal loci. Yet, genomic surveys have identified relatively few genes that
consistently explain variation in disease outcomes in humans. A primary explanation for this gap is
context-dependence: a gene may underlie parasite resistance at low but not high doses, or against one
parasite strain but not others. This hypothesis argues that we cannot reliably detect the genes that
matter for resistance without accounting for the genetic and environmental context in which hosts
encounter their parasites. Ongoing projects associated with my parent award are addressing this need
by characterizing genetic variation for parasite resistance across contexts using diverse host and
parasite genotypes sampled from nature. Our powerful model system - the nematode Caenorhabditis
elegans and its natural microsporidian parasites in the genus Nematocida – allows us to conduct highly
controlled and replicated experiments across multiple contexts. We apply high-throughput
phenotyping, experimental evolution, and experimental epidemiology to 1) characterize genetic
variation in parasite resistance in natural populations, 2) evaluate the impact of parasite genotype on
the expression of this genetic variation, and 3) examine the sensitivity of resistance genes to relevant
environmental variables. Our efforts identified dose – the number of parasites a host encounters - as a
major driver of the expression of genetic variation for resistance. We have designed key follow-up
experiments to characterize the dose-dependency of resistance across host genotypes, and these
experiments require precise estimates of parasite abundance within hosts and in their surrounding
environment. Accordingly, I am requesting a supplement to this parent award to purchase a QIAcuity
instrument for digital PCR to increase our precision, replication, and range of sample types for these
experiments. This equipment will directly augment the impact of our projects on the scientific
community and provide long-term support to my research program and department.

## Key facts

- **NIH application ID:** 11082780
- **Project number:** 3R35GM137975-05S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Amanda K Gibson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $59,754
- **Award type:** 3
- **Project period:** 2020-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11082780

## Citation

> US National Institutes of Health, RePORTER application 11082780, A general test of the genetic basis of parasite resistance across genetic and environmental contexts (3R35GM137975-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11082780. Licensed CC0.

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