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Exploring the function of a novel tyrosine kinase like (TKL) protein in Toxoplasma endodyogeny

Award Number: R21AI162606
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: 05/03/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Exploring the function of a novel tyrosine kinase like (TKL) protein in Toxoplasma endodyogeny - PROJECT SUMMARY/ABSTRACT Toxoplasma gondii is an important human pathogen that divides by a unique mode of cell division called endodyogeny that is quite distinct from binary fission that occurs in mammalian cells. Since Toxoplasma division is divergent from higher eukaryotes, a better understanding of this complex process and identification of its key components and their mode of regulation would potentially open doors for selective strategies to disrupt infection. TgTKL4 is a member of tyrosine kinase like (TKL) family protein in Toxoplasma that localizes to parasite cytoplasm with its expression mainly confined to synthesis (S), mitosis/cytokinesis (M/C) phases of the cell cycle. Interestingly, loss of this kinase causes defects in cell division that results in misshapen parasites with compromised fitness and attenuated virulence. Specifically, TgTKL4 null mutants with abnormal morphology display significant defects in in vitro propagation suggesting loss of this kinase affects one or more stages of Toxoplasma lytic cycle. Since TgTKL4 is a cell-cycle regulated kinase and parasites deficient in this enzyme show abnormal shape, we hypothesize that this kinase is a part of the signaling network that dictates parasite morphology during endodyogeny. To further understand the role of this novel TKL kinase in parasite replication, we propose to: (1) Identify substrates of TgTKL4; and (2) Determine the role of TgTKL4 in Toxoplasma endodyogeny. Thus, our proposed work will help us understand the precise function of TgTKL4 and signaling network associated with this kinase during cell division that determines parasite morphology.


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: 2025 ( Subtotal = -$17,347 )
2025	2023	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Allergy and Infectious Diseases Research	000	2	9/10/2025	NON-COMPETING CONTINUATION	-$17,347
														Subtotal = -$17,347

Issue Date FY: 2023 ( Subtotal = $240,000 )
2023	2023	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Allergy and Infectious Diseases Research	001	2	3/8/2023	NON-COMPETING CONTINUATION	$240,000
2023	2022	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Allergy and Infectious Diseases Research	000	1	3/6/2023	NEW	$0
														Subtotal = $240,000

Issue Date FY: 2022 ( Subtotal = $200,000 )
2022	2022	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Allergy and Infectious Diseases Research	000	1	5/3/2022	NEW	$200,000
														Subtotal = $200,000

Grand Total All Awards = $422,653

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Exploring the function of a novel tyrosine kinase like (TKL) protein in Toxoplasma endodyogeny

Award Number: R21AI162606

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: 05/03/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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