# Deciphering the composite S-phase in Toxoplasma gondii

> **NIH NIH R21** · UNIVERSITY OF SOUTH FLORIDA · 2024 · $187,500

## Abstract

Abstract
Apicomplexa parasites contribute significantly to human disease burden, including ~1/3 of human populations
permanently infected with Toxoplasma gondii. Existing treatments are limited and often toxic to the most affected
population of immunocompromised patients. We need a profound knowledge of parasite biology to develop
efficient anti-parasitic drugs. Our group focuses on the studies of cell cycle mechanisms that are central to
parasite survival and offer a wealth of druggable targets. The cell cycle program orchestrates cell division and
ensures the inheritance of the genetic material. Apicomplexan cell cycles are strikingly different from the cell
cycles of their hosts. Although T. gondii tachyzoite divides by endodyogeny that resembles a binary division of
the conventional eukaryotes, there are substantial differences in cell cycle organization and regulation. It includes
the atypical S-phase of Toxoplasma endodyogeny, which is a primary focus of our study. The need for
appropriate tools to examine the intricacy of the apicomplexan cell cycle and unconventional regulators
significantly impedes the related studies. To fill a major gap in our knowledge of the essential biology of
apicomplexan parasites and boost the Toxoplasma cell cycle studies, we engineered a new Fluorescent
Ubiquitination-based Cell Cycle Indicator (FUCCI) probe.
In the Aim 1 experiments, we will test the hypothesis that Toxoplasma endodyogenic cell cycle includes a
composite S/M/C phase that runs for nearly half of the division cycle. Using our new ToxoFUCCI probes, we
will determine how the intertwined S/M/C phase is organized. In Aim 2, we will determine the mechanism of
the S-phase regulation. Designed experiments will test the hypothesis that, contrary to conventional S-phase
cyclin dependent kinase (Cdk), controlled release of the sequestrated Cdk-related kinase TgCrk5 regulates DNA
replication in the tachyzoites. Using the conditional expression model of TgCrk5, we will determine the functions
of the sequestered and the nuclear TgCrk5 and identify the TgCrk5 substrates. Given that T. gondii lacks
conventional S-Cdk substrates, we expect to discover a novel TgCrk5 network. The project will advance our
knowledge of the fundamental process of parasite survival and have a high potential to discover future efficient
drug targets.

## Key facts

- **NIH application ID:** 10908661
- **Project number:** 5R21AI178797-02
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Elena Suvorova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $187,500
- **Award type:** 5
- **Project period:** 2023-08-16 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908661

## Citation

> US National Institutes of Health, RePORTER application 10908661, Deciphering the composite S-phase in Toxoplasma gondii (5R21AI178797-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908661. Licensed CC0.

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