Thursday, July 3, 2025 7/3/2025

Defining the role of calcium-binding proteins in the human parasite Toxoplasma gondii

Award Number: SC3GM121223
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2023

Group Awards By:

View Award Description

Defining the role of calcium-binding proteins in the human parasite Toxoplasma gondii - Project Summary Toxoplasma gondii is a unicellular, obligate intracellular parasite that can infect almost any mammal or bird. Once inside the host organism it can invade and replicate within any nucleated cell and access privileged spaces such as the central nervous system. It is estimated that T. gondii infects 30% of humanity. Acute T. gondii infection (Toxoplasmosis) is characterized by uncontrolled proliferation of the parasite (the lytic cycle) where it repeatedly invades and replicates within host cells and then searches for new host cells to invade. Calcium signaling initiates the major events of the lytic cycle: motility, invasion, and egress. Oscillatory calcium changes in the parasite's cytosol allows for elegant responses in highly complex, and sometimes diverging pathways. While much is known regarding the downstream events that occur as a result of this specific calcium signaling, it is unknown how this parasite, and the many parasites it is related to, regulates calcium fluctuations at a molecular level, to induce highly specific responses. EF-hand containing calcium-binding proteins (CBPs) are a major mechanism used for controlling the intracellular free calcium concentration in eukaryotic cells. We hypothesized that a subset of highly expressed CBPs acts as key regulators of the diverging pathways that sustain the lytic cycle in T. gondii. We will determine the spatial and temporal patterns of transcript and protein expression in order to determine the regulatory network by which they drive and sustain invasion-linked traits (e.g., motility, invasion, and host cell egress). Expression patterns will be measured using qRT-PCR (transcript abundance). T. gondii-specific antibodies will be made and used for the quantification of protein expression using Western blotting. Spatial expression patterns of protein abundance will be conducted using immuno- fluorescent microscopy. The expression levels of CBPs will be manipulated both by constitutive overexpression or knock out of the genes in tachyzoites. CBP genes will be over-expressed using T. gondii-specific over- expression vectors. Knockout mutants for the CBPs will be obtained by homologous recombination using newly designed CRISPR/Cas9 gene-editing vectors that have been optimized specifically for T. gondii. Phenotypic characterization of mutants will include analysis of intracellular calcium regulation using newly designed parasites that constitutively express a fluorescent intracellular calcium probe (Genetically Encoded Calcium Indicator, or GECI-parasites). In total, this research will fully evaluate the spatial and temporal regulation of calcium by CBPs throughout the lytic stage, making subsequent strategies of parasite disruption through targeting of CBPs a compelling and realistic strategy for treating T. gondii infections.


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: 2024 ( Subtotal = -$90 )
2024	2020	CALIFORNIA STATE UNIVERSITY LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	11/9/2023	NON-COMPETING CONTINUATION	-$90
														Subtotal = -$90

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	2/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $110,625 )
2020	2020	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	4	3/17/2020	NON-COMPETING CONTINUATION	$11,063
2020	2020	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	1/31/2020	NON-COMPETING CONTINUATION	$99,562
														Subtotal = $110,625

Issue Date FY: 2019 ( Subtotal = $110,625 )
2019	2019	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	1/10/2019	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2018 ( Subtotal = $110,625 )
2018	2018	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	5/11/2018	NON-COMPETING CONTINUATION	$11,063
2018	2018	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	1/19/2018	NON-COMPETING CONTINUATION	$99,562
														Subtotal = $110,625

Issue Date FY: 2017 ( Subtotal = $105,875 )
2017	2017	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	1/30/2017	NEW	$105,875
														Subtotal = $105,875

Grand Total All Awards = $437,660

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Defining the role of calcium-binding proteins in the human parasite Toxoplasma gondii

Award Number: SC3GM121223

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer