# Structure and Function of the Conoid in Toxoplasma

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $738,388

## Abstract

ABSTRACT
The intracellular parasite Toxoplasma gondii provides a model for studying structure-function relationships of
conserved features of the phylum Apicomplexa. Several apicomplexan parasites are responsible for severe
human diseases that persist despite efforts to control them. One limitation is that we lack fundamental
understanding of essential parasite processes that could be used to develop new and/or improved therapies.
Our work is motivated by the goal of understanding the unique complexity of structural features that form the
cytoskeleton of apicomplexan parasites. Among the conserved features is the apical complex consisting of
specialized tubulin rich cytoskeletal structure called the conoid, which provides a platform for other motor
proteins and conduit for protein secretion. Toxoplasma has one of the most elaborate conoid structures, and
while it is reduced in complexity in other apicomplexans, many of the core proteins are conserved. In T. gondii,
the apical complex consists of several preconoidal rings, a prominent conoid made up of specialized
microtubular conoidal fibers, two long intraconoidal microtubules, and the base formed by the apical polar ring.
To date, only a few proteins have been studied functionally, although it is anticipated that conoid is comprised
of ~100 proteins. Progress has been limited by the laborious process of identifying and functionally
characterizing proteins in conoid, most of which have no orthologs in model systems. The proposed project
aims to elevate the state of knowledge of the composition and function of the conoid by identifying all of the
major proteins and localizing them in a composite 3-D structure of the organelle. This goal will be achieved
through cell fractionation, quantitative mass spectrometry, and high-resolution single-particle cryo-electron
microscopy (cryo-EM). We will also functionally characterize a number of new conoid proteins to define their
roles in conoid assembly and function. These findings are expected to provide a near-complete atomic model
of all the major components of the conoid, define the role of essential components in its assembly and function,
and provide a framework for comparative studies of other apicomplexans.

## Key facts

- **NIH application ID:** 10777678
- **Project number:** 1R01AI179885-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** L. David Sibley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $738,388
- **Award type:** 1
- **Project period:** 2023-11-07 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10777678

## Citation

> US National Institutes of Health, RePORTER application 10777678, Structure and Function of the Conoid in Toxoplasma (1R01AI179885-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10777678. Licensed CC0.

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