# Divergent Calcium Channels of the Apicomplexan parasite Toxoplasma gondii

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2023 · $624,755

## Abstract

PROJECT SUMMARY/ABSTRACT
Ca2+ ions impact almost every aspect of cellular life. Ca2+ signaling begins with the opening of Ca2+ channels
in either the plasma membrane (PM) or the endoplasmic reticulum (ER) and results in a dramatic increase in
the physiologically low (<100 nM) cytosolic Ca2+ levels. The temporal and spatial Ca2+ levels are exquisitely
regulated and enable the precise and specific activation of critical biological processes like changes in gene
expression, cell differentiation, muscle contraction, fertilization, or secretion of neurotransmitters to name a
few. Ca2+ signaling regulates pathogenic pathways of apicomplexan parasites like Toxoplasma gondii which
infects approximately one third of the world’s population. T. gondii is an opportunistic pathogen of
immunocompromised patients like HIV-infected individuals, fetuses, and organ transplant recipients. As an
obligate intracellular pathogen, T. gondii replicates inside cells and the clinical manifestations of
toxoplasmosis are a direct result of its growth within cells and its dissemination. T. gondii relies on Ca2+ signals
for the stimulation of specific features of its infection cycle and several Ca2+ signaling elements play essential
roles in its parasitic cycle. However, the fundamental elements that initiate Ca2+ signals in T. gondii are largely
unknown yet are likely essential for its viability and virulence. Discovery and characterization of the molecules
that initiate Ca2+ signaling in T. gondii are hence central for the understanding of its pathogenesis. Active egress
of T. gondii from host cells is critical for dissemination of the infection and our prior work has provided
conclusive evidence that there is a cytosolic Ca2+ peak preceding egress. This parasitic cytosolic increase
arises from release from intracellular stores, likely the endoplasmic reticulum. It is puzzling, however, that
intracellular parasites replicate surrounded by the low host cytosolic Ca2+ but still store sufficient Ca2+ in their
ER to trigger egress. Upon host cell rupture, extracellular Ca2+ influx across the PM contributes to a second
Ca2+ peak enhancing motility of parasites, which then exit and seek another host cell to invade. Our hypothesis
is that PM Ca2+ entry is essential for refilling of intracellular Ca2+ stores, and both intra and extracellular sources
are necessary for triggering the cascade of molecular events that lead to the stimulation of parasitic functions
like motility, secretion of adhesins, invasion of host cells, egress and dissemination. In this proposal we aim to
characterize the proteins that enable PM Ca2+ influx. There is almost no information about the functional
characteristics and roles of Ca2+ channels in T. gondii. This lack of knowledge could be due to lack of appropriate
tools, techniques, and training in electrophysiology within the molecular parasitology field. We address this
void with a collaboration with a mammalian electrophysiologist and a modeler. Channe...

## Key facts

- **NIH application ID:** 10681807
- **Project number:** 1R01AI174600-01A1
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Silvia N Moreno
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $624,755
- **Award type:** 1
- **Project period:** 2023-02-07 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10681807

## Citation

> US National Institutes of Health, RePORTER application 10681807, Divergent Calcium Channels of the Apicomplexan parasite Toxoplasma gondii (1R01AI174600-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10681807. Licensed CC0.

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