# Regulation of Host Signaling by Parasitoid Venom Proteins

> **NIH NIH R35** · ILLINOIS STATE UNIVERSITY · 2022 · $234,259

## Abstract

The precise regulation of intra- and inter-cellular signaling events is crucial for the function of biological
systems and plays an essential role in human health. Deregulated signaling can perturb cell function by
altering the timing or strength of signal activity and can contribute to the pathogenesis of multiple diseases.
Signal regulation is accomplished by a variety of intrinsic mechanisms, but signaling can also be manipulated
by extrinsic factors including factors derived from other organisms or the environment. Interorganismal signal
regulation is often observed during infection, in which a parasite can utilize virulence factors in order to alter
host signaling events. In my lab we use the Drosophila-parasitoid wasp host-parasite system as a model to
study the mechanisms used by parasites to manipulate host signaling. These parasitoids contain virulence
proteins in their venoms, and work from my lab has demonstrated that parasitoid venom proteins can modify
conserved signaling mechanisms including signal transduction pathways and second messenger systems in
their hosts. Understanding the mechanistic basis of these venom protein activities will provide a powerful tool
to study the regulation of signaling events, and will allow us to gain novel insight into conserved signaling
mechanisms in Drosophila, an important model of human health. The objective of our research is to leverage
this system to uncover novel mechanisms underlying signal regulation and to achieve these goals, research in
my lab will focus on: 1) Identifying the molecular mechanisms used by parasitoid wasps to inhibit conserved
signaling pathways in their Drosophila hosts. We have found that distinct parasitoid species target specific
signaling pathways in their hosts, including species that specifically inhibit the JAK-STAT, NFκB and JNK
signal transduction pathways. These pathways play vital roles in human health and this research will provide
important insight into their regulation. 2) Characterizing the ability of predicted dominant negative proteins to
regulate host signaling. Our bioinformatic analyses have identified several putative dominant negative proteins
within parasitoid venom. We predict that these proteins will deregulate diverse signaling activities including
immune receptor signaling and cytoskeletal rearrangements. From these experiments we will gain a better
understanding of the roles played by the targeted proteins in a range of signaling events. 3) Investigating the
basis for the tissue specificity of parasitoid venom activity. We have found that the ability of parasitoids to
regulate signaling is highly tissue specific within the host. These experiments will explore the basis of this
observation and provide insight into the mechanisms that underlie tissue specific signal regulation. The
knowledge gained from this research will help to elucidate general principles underlying the regulation of
signaling, and will provide specific information about multi...

## Key facts

- **NIH application ID:** 10439636
- **Project number:** 5R35GM133760-04
- **Recipient organization:** ILLINOIS STATE UNIVERSITY
- **Principal Investigator:** Nathan Terry Mortimer
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $234,259
- **Award type:** 5
- **Project period:** 2019-08-15 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439636

## Citation

> US National Institutes of Health, RePORTER application 10439636, Regulation of Host Signaling by Parasitoid Venom Proteins (5R35GM133760-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10439636. Licensed CC0.

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