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Structure and Function of the Conoid in Toxoplasma

Award Number: R01AI179885
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/07/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2028

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Structure and Function of the Conoid in Toxoplasma - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $708,984 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	3	11/26/2025	NON-COMPETING CONTINUATION	$708,984
														Subtotal = $708,984

Issue Date FY: 2025 ( Subtotal = $706,598 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	2	1/8/2025	NON-COMPETING CONTINUATION	$706,598
														Subtotal = $706,598

Issue Date FY: 2024 ( Subtotal = $738,388 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	1	11/7/2023	NEW	$664,549
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	1	9/3/2024	NEW	$73,839
														Subtotal = $738,388

Grand Total All Awards = $2,153,970

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Structure and Function of the Conoid in Toxoplasma

Award Number: R01AI179885

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 11/07/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2028

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