# Kinase regulation of trafficking at the Toxoplasma intravacuolar network

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $403,782

## Abstract

PROJECT SUMMARY/ABSTRACT
 Toxoplasma gondii has the remarkable ability to infect virtually any cell type of almost all warm-blooded
animals and is arguably the most successful parasite on earth, having infected an estimated one-third of
humans globally. While initial infection typically resolves without complication, the parasite is able to persist
for the life of its host, and can re-emerge in the immunocompromised and immunosuppressed to cause fatal
disease. Toxoplasma, like other apicomplexan parasites, must invade a host cell to survive and replicate.
 Once inside a host cell, the parasite survives and replicates within a specialized organelle called the
parasitophorous vacuole. Disruption of the vacuole results in parasite death, and the parasite secretes a
battery of proteins into the vacuole to facilitate its biogenesis and regulate trafficking of nutrients and
effector proteins. A principle structure within the parasitophorous vacuole is the intravacuolar network of
membranous tubules (the IVN), which is thought to act as a major trafficking apparatus. IVN biogenesis is
formed by the direct action of oligomeric complexes of parasite proteins and mutants that disrupt the IVN
show reduced virulence in animal models of infection. We have identified a parasite-specific protein kinase
that regulates the membrane association of a subset of the proteins that associate with the parasitophorous
vacuolar and IVN membranes, and deletion of this kinase results in vacuoles with aberrant IVN tubulation.
While we have identified the kinase substrates and the sites of phosphorylation, the interactions that are
regulated by this phosphorylation are unknown. The goal of the proposed studies is to determine the
precise molecular mechanisms by which phosphorylation regulates the inter- and intra-molecular
interactions that drive IVN biogenesis. First, we will determine how the components of the protein
complexes that drive IVN biogenesis change as the complexes progress through the parasite secretory
system and insert into the IVN membrane. We will use molecular genetic, cellular, and biochemical methods
to determine the molecular mechanisms by which phosphorylation regulates these protein-protein
interactions to facilitate IVN development. Furthermore, we will use innovative biophysical methods to
generate the first structural models of these critical parasite protein complexes to determine the biophysical
mechanism by which they induce IVN formation.

## Key facts

- **NIH application ID:** 9942325
- **Project number:** 1R01AI150715-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Michael Lloyd Reese
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,782
- **Award type:** 1
- **Project period:** 2020-03-17 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942325

## Citation

> US National Institutes of Health, RePORTER application 9942325, Kinase regulation of trafficking at the Toxoplasma intravacuolar network (1R01AI150715-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9942325. Licensed CC0.

---

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