# Mining natural infection variation to find the genetic basis of coevolution between vertebrate hosts and helminth parasites

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $382,090

## Abstract

Project Summary/Abstract
Helminths (i.e., parasitic worms) infect all vertebrate taxa. Hosts generally evolve to block, purge, or limit the
negative effects of infection, and parasites evolve to hide from or manipulate host physiology. Numerous
molecules and cellular pathways are known to modulate interactions between vertebrate hosts and helminth
parasites, but little is known about how the evolution of immunity and infectivity influences natural variation in
parasite infections. Data on the particular genetic differences that underlie evolved differences in immunity are
similarly limited. Over the next five years, my lab will describe the genetic mechanisms and evolutionary history
of coevolution between a small fish with abundant ecological and genetic resources, the threespine stickleback
(Gasterosteus aculeatus), and one of its cestode parasites. This work is facilitated by lab-based protocols to
efficiently intercross cestodes, expose sticklebacks to controlled doses of these pathogens, co-culture host and
immune cells in vitro, and assays of host immunity and parasite viability. We can not only identify and measure
heritable traits that affect infection specificity and intensity, but also apply modern genetic approaches to
dissect the molecular mechanisms underlying this naturally selected variation. Our preliminary data show that
threespine sticklebacks repeatedly evolved to block the initial establishment and subsequent growth of
cestodes, but that the mechanisms of resistance vary across populations. Cestodes also evolved to counteract
the defenses of their local hosts, eventually leading to specialization on a subset of hosts. We will use forward
genetics to map the chromosomal loci associated with pathogen-driven host evolution, while crossing diverged
cestode populations will uncover loci evolving due to host-driven selection. This work will be complemented
with pharmacological and transgenic manipulations of candidate genes and molecular pathways, as well as
forays into natural settings where we will use both experimental transplants and time-series data to understand
how coevolution varies due to ecological and spatial constraints. Perhaps most exciting, there are several
closely related stickleback species and cestode species that, despite millions of years of divergence, remain
interfertile, and which enable us to characterize the genetics of coevolution across both micro- and
macroevolutionary timescales.

## Key facts

- **NIH application ID:** 10456130
- **Project number:** 5R35GM142891-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jesse Nathaniel Weber
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,090
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456130

## Citation

> US National Institutes of Health, RePORTER application 10456130, Mining natural infection variation to find the genetic basis of coevolution between vertebrate hosts and helminth parasites (5R35GM142891-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10456130. Licensed CC0.

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