# Multiscale analysis of MyosinA-based motility in Toxoplasma gondii

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2021 · $539,668

## Abstract

Toxoplasmic encephalitis (TE) is a life-threatening infection of the brain in AIDS patients caused by the
opportunistic pathogen, Toxoplasma gondii. Drugs are available to treat acute T. gondii infection in these
patients, and to suppress its re-emergence in those who are chronically infected, but for many patients the
adverse effects of the drugs are severe, resulting in their discontinuation. Thus, there is a need to develop new,
better-tolerated drugs to treat AIDS-related TE. This, in turn, requires a better understanding of the biology of T.
gondii and the mechanisms underlying its virulence, so that critical points of vulnerability in the parasite’s life
cycle can be identified and targeted.
 The life cycle stage of T. gondii responsible for disease pathogenesis, the tachyzoite, is highly motile.
Tachyzoite motility is required for host cell invasion, migration across biological barriers, and dissemination
through host tissues. T. gondii MyosinA (TgMyoA) is an unconventional myosin motor protein that plays a central
role in parasite motility, and tachyzoites lacking TgMyoA are completely avirulent. The overarching goals of this
project are to advance our mechanistic understanding of tachyzoite motility and to test whether small molecules
targeting the motility machinery can ameliorate disease in an animal model of infection. The Specific Aims are
to: (1) Determine how altering specific aspects of TgMyoA motor function affects parasite motility, by
characterizing how recently identified small-molecule inhibitors of the TgMyoA motor affect its biomechanical
activity and connecting these changes in motor function to effects on parasite 3D motility; and (2) Determine how
inhibiting TgMyoA impacts parasite dissemination and disease progression, in vivo, to better understand the role
of TgMyoA and parasite motility during infection and to provide the first direct evaluation of the TgMyoA motor
as a drug target for preventing or treating toxoplasmosis.
 Recent technological advances have created an unprecedented opportunity to manipulate and study parasite
motility in a truly integrated way. This project will capitalize on that opportunity across the full range of scales –
from the biochemical and biophysical properties of the TgMyoA motor, to the characteristics of parasite motility
within a model 3D extracellular matrix, to the ability of parasites to disseminate and cause disease in infected
animals. The results will therefore significantly enhance our mechanistic understanding of how T. gondii moves
within its hosts to cause disease. Because TgMyoA is both essential for virulence and distinctly different from
human myosins it is also a potential target for drug development; by directly testing the druggability of TgMyoA
in an animal model of infection, this work will contribute to ongoing efforts to develop new and improved
chemotherapeutics for managing T. gondii infections in AIDS patients.

## Key facts

- **NIH application ID:** 10064612
- **Project number:** 5R01AI139201-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** GARY E WARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $539,668
- **Award type:** 5
- **Project period:** 2018-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064612

## Citation

> US National Institutes of Health, RePORTER application 10064612, Multiscale analysis of MyosinA-based motility in Toxoplasma gondii (5R01AI139201-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10064612. Licensed CC0.

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