# Role of redundant secreted effectors of Toxoplasma gondii that drive host cell cycle progression

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2020 · $228,000

## Abstract

Project Summary
Toxoplasma gondii is arguably one of the most successful parasitic protozoans on the planet. It
is estimated that T. gondii infects approximately a third of humanity (~2 billion people) and
nearly half of all warm-blooded animals. Once established, infection is lifelong and
characterized by the presence of semi-dormant tissue cysts typically in muscle and neural
tissues. As host conditions change, T. gondii has the capacity to reactivate and induce multiple
rounds of recurrent parasitemia, a fact which becomes an issue of serious concern in an aging
population or in individuals with compromised immune systems. Currently, there are no drugs
available that can effectively treat the chronic stage of infection and therapies currently in use
against acute infection are often accompanied by serious side effects. It is therefore important,
especially as population's age, to generate new methods and compounds to treat this disease.
Upon invasion of its host cell, Toxoplasma induces a massive reorganization of the host cell
transcriptional program and as a result, major pathways related to metabolism, immunity and
the cell cycle become activated. T. gondii has been show to initiate modification of its host cell
environment through the regulated secretion of its various secretory organelles (micronemes,
rhoptries, dense granules). The dense granules, originally characterized as serving only to
condition the parasite vacuole to be a feeding organelle, are now considered a reservoir of
various host nuclear targeted parasite effectors with diverse targets and functions. These
proposed studies aim to characterize a newly identified parasite effector of the dense granules
we have termed ICC1 for inducer of cell cycle gene 1. We have demonstrated that ICC1 traffics
to the host cell nucleus soon after infection and induces the expression of a multitude of genes
involved in progression of the host cell cycle into S-phase. Additionally we have found that T.
gondii also has 2nd redundant effector to alter the host cell cycle via that is released from its
rhoptry organelle and which we have identified as the host nuclear targeted phosphatase PP2C-
hn. To advance our knowledge of ICC1 and PP2C-hn's function, we propose to perform a series
of immunoprecipitation and mass spectrometry experiments in order to identify the principal host
targets and determine the functional significance of this interaction as it relates to cell cycle
progression. The results of this proposal will provide the first mechanistic basis for the
modulation of the host cell cycle by a protozoan parasite and may give additional insight into the
basic function of our own cells.

## Key facts

- **NIH application ID:** 9849182
- **Project number:** 5R21AI142431-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** RONALD DREW ETHERIDGE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,000
- **Award type:** 5
- **Project period:** 2019-01-10 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849182

## Citation

> US National Institutes of Health, RePORTER application 9849182, Role of redundant secreted effectors of Toxoplasma gondii that drive host cell cycle progression (5R21AI142431-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849182. Licensed CC0.

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