# Is Calcium the Gear Shift? The Role of Calcium-Mediated TgMyoA Phosphorylation in Toxoplasma Gondii Motility

> **NIH NIH F31** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $15,158

## Abstract

Project Summary
Toxoplasma gondii is a protozoan parasite that infects between 30-50% of the world’s population. The parasite
causes toxoplasmosis, which is a potentially life-threatening disease in the developing fetus and
immunocompromised individuals. Currently available drugs to treat toxoplasmosis often cause adverse side
effects that lead to discontinuation of treatment, highlighting the need for new and improved treatments. One
potential target for drug development is the motile system of T. gondii, as motility is essential for virulence. T.
gondii uses its unique form of cellular motility to invade host cells, traverse numerous biological barriers, and
disseminate throughout the host organism. An unconventional myosin motor protein, TgMyoA, drives motility,
and this project will test the hypothesis that motor function and parasite motility are regulated by calcium-
mediated phosphorylation of TgMyoA. Aim 1 seeks to investigate the role in motility of a calcium-dependent
protein kinase (TgCDPK3) that was recently shown to phosphorylate TgMyoA. A recently developed 3D motility
assay will be used to determine the specific effect(s) that disruption of TgCDPK3 has on motility, and recombinant
TgMyoA expression to establish how phosphorylation affects motor function. As TgCDPK3 phosphorylates many
parasite proteins in addition to TgMyoA, Aim 1 will also determine whether expressing TgMyoA with
phosphomimetic amino acids at the sites normally phosphorylated by TgCDPK3 is sufficient to overcome the
motility defects seen in parasites lacking functional TgCDPK3. Aim 2 will determine if the oscillations in parasite
intracellular calcium levels observed during motility play a role in regulating the regular oscillations in parasite
velocity seen in 3D. Using calcium indicator-expressing parasites, the calcium oscillations will be altered
pharmacologically (e.g., with caffeine, which lengthens the calcium oscillations) to determine whether the velocity
oscillations are correlation and/or causative. Combined, the two Aims will provide novel insights into the role of
calcium and TgMyoA phosphorylation in motility regulation. Understanding the regulation of TgMyoA will be
critical to determining how to most effectively target motility for drug development.

## Key facts

- **NIH application ID:** 10380883
- **Project number:** 5F31AI145214-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Rachel Stadler
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $15,158
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-09-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380883

## Citation

> US National Institutes of Health, RePORTER application 10380883, Is Calcium the Gear Shift? The Role of Calcium-Mediated TgMyoA Phosphorylation in Toxoplasma Gondii Motility (5F31AI145214-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10380883. Licensed CC0.

---

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