# Cytoskeletal machinery driving invasion by the human pathogen, Toxoplasma gondii.

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2022 · $400,844

## Abstract

Project Summary:
Approximately 20% of the people on Earth are permanently infected with the unicellular parasite,
Toxoplasma gondii. T. gondii is one of the leading causes of congenital neurological defects in
humans, and an agent for devastating opportunistic infections in immunocompromised individuals.
Ocular toxoplasmosis is one of the most common retinal infections and can lead to blindness. As an
obligate intracellular parasite, T. gondii must first invade cells of its host in order to replicate. In the
preliminary study, we found that the disruption of an iconic structure in T. gondii, the conoid, is linked to
drastically impaired invasion. This is an aspect of invasion that has not been explored, as previous
work on invasion has mainly centered on the regulation and activity of the actomyosin motor complex
and protein secretion from specialized membrane-bound organelles. To explore this new direction, we
propose two complementary aims to (a) determine the function of the conoid in host cell invasion (Aim
1), and (b) elucidate how this novel cytoskeletal complex is constructed (Aim 2). Using the mutants we
have generated, Aim 1 will determine whether the conoid facilitates invasion by secretion, motility,
directly assisting the physical interaction between the parasite and the host cell during attachment, or
overcoming the cortical tension of the host cell. Aim 2 will identify and characterize structural
determinants of the conoid by integrating gene discovery with structural and functional analyses. We
will combine state of the art imaging, biophysical, biochemical, and evolutionary approaches. This
comprehensive strategy will greatly enhance our ability to identify novel components in this unique
structure as drug targets.

## Key facts

- **NIH application ID:** 10322763
- **Project number:** 5R01AI132463-05
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Ke Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,844
- **Award type:** 5
- **Project period:** 2018-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322763

## Citation

> US National Institutes of Health, RePORTER application 10322763, Cytoskeletal machinery driving invasion by the human pathogen, Toxoplasma gondii. (5R01AI132463-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10322763. Licensed CC0.

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