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

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2020 · $397,039

## Abstract

Project Summary
A central goal of infectious disease research is to identify the genes that determine an individual’s
susceptibility to parasites. Biomedical research has made substantial progress towards this goal by
establishing molecular and genetic approaches for detecting alleles associated with parasite resistance
and host health. Pursuing these alleles across many organisms, including humans, has revealed an
underlying problem: an allele may strongly predict parasite resistance in one environment but not
others, or against one parasite strain but not others. This context-dependence might explain why
genomic surveys have rarely been able to identify alleles that consistently explain disease
susceptibility in humans. In addition, there is immense genetic diversity for parasite resistance in
host populations, and this diversity is not represented in the few inbred lab lines used to identify
alleles in model organisms. Therefore, to gain a general understanding of the alleles that matter for
parasite resistance, we must account for the genetic diversity and environmental complexity present
in the natural settings in which hosts encounter their parasites. In the next five years, research in my
lab will address this need by characterizing the genetic basis of parasite resistance across genetic and
environmental contexts using diverse host and parasite genotypes sampled from nature. My lab
group is well-positioned for this work: we have expertise in the nematode Caenorhabditis elegans and
its most prevalent natural parasite, the microsporidia Nematocida parisii. This powerful model
system enables us to quickly and cheaply perform highly replicated experiments and genomic
analyses to examine genetic variants across contexts. Recent efforts to collect wild C. elegans isolates
and parasite strains have provided us with the broad sampling of natural variation necessary for our
goal. Here, I propose to 1) characterize the alleles that contribute to parasite resistance in natural
populations using high-throughput phenotyping, genome-wide association surveys, and high-
resolution quantitative trait mapping based on public collections of fully-sequenced wild C. elegans
genotypes (>300) and recombinant inbred lines based on multiple wild parents. I then propose to
use experimental evolution, phenotype mapping, and transgenic host lines to: 2) evaluate the impact
of parasite genotype on the expression of genetic variation for parasite resistance, and 3) examine the
sensitivity of resistance alleles to relevant environmental variation, specifically in microbial diet and
population density. This proposed work forms the foundation of my research program targeted at
establishing general frameworks for identifying the diversity of alleles that can determine parasite
resistance and evaluating their contribution to host health in real world settings. This work will
support efforts to use genetic data to predict the health of individuals and populations.

## Key facts

- **NIH application ID:** 10027549
- **Project number:** 1R35GM137975-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Amanda K Gibson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,039
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10027549

## Citation

> US National Institutes of Health, RePORTER application 10027549, A general test of the genetic basis of parasite resistance across genetic and environmental contexts (1R35GM137975-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10027549. Licensed CC0.

---

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