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Role in pathogenesis and parasite cell biology of the trans-sialidase from Trypanosoma cruzi, the agent of Chagas Disease

Award Number: R01AI104531
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Chagas disease affects an estimate of 1,600,000 people in Argentina. This chronic disabling disease also constitutes a major health issue in Latin America. Its causative agent, the protozoan flagellate Trypanosoma cruzi, expresses a virulence factor known as trans-sialidase (TS) that cover the inability of the parasite to perform sialic acids synthesis de novo. TS transfer the sialyl residue from the mammal host proteins to the parasite surface, thus preventing its lysis by serum components and enabling the parasite to invade cells where to replicate. This virulence factor is also shed to the milieu being found in the bloodstream thus acting far from the infectious site/s. TS induce several alterations on the immune system including apoptosis of cellular components and modulation of CD4 T cells both at their elicitation and effector stages. We recently defined the distribution of the parasite surface protein components where the TS and mucins, the main acceptor of the sialyl residue transferred, are located in separate domains. Similarly happens with other unrelated proteins. Some proteins use the contractile vacuole as a pathway to reach the surface while others not. In this project, we propose to study the protein requirements to use this trafficking pathway, or been excluded from it, and the process associated with their final fate on different domains at the parasite surface. Because the TS constitute a central virulence factor of the parasite we will obtain parasites devoid of its expression to assess their ability to invade cells, replicate and induce pathogenesis in mammals. The ability of TSs to modulate the TH1/TH2/TH17 balance will be analyzed at the light of recent findings from our lab that might explain previous results from other researchers and been associated with the outcome of the infection.


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: 2023 ( Subtotal = $135,000 )
2023	2023	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445	SAN MARTIN	BUENOS AIRES			ARG	Allergy and Infectious Diseases Research	000	10	7/14/2023	NON-COMPETING CONTINUATION	$135,000
														Subtotal = $135,000

Issue Date FY: 2022 ( Subtotal = $135,000 )
2022	2022	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445, EDIFICIO 24, CC 30	SAN MARTIN	BUENOS AIRES			ARG	Allergy and Infectious Diseases Research	000	9	3/25/2022	NON-COMPETING CONTINUATION	$135,000
														Subtotal = $135,000

Issue Date FY: 2021 ( Subtotal = $133,800 )
2021	2021	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445, EDIFICIO 24, CC 30	SAN MARTIN	BUENOS AIRES			ARG	Allergy and Infectious Diseases Research	000	8	4/16/2021	NON-COMPETING CONTINUATION	$133,800
														Subtotal = $133,800

Issue Date FY: 2020 ( Subtotal = $133,800 )
2020	2020	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445, EDIFICIO 24, CC 30	SAN MARTIN	BUENOS AIRES	B1650KNA		ARG	Allergy and Infectious Diseases Research	000	7	3/18/2020	NON-COMPETING CONTINUATION	$133,800
														Subtotal = $133,800

Issue Date FY: 2019 ( Subtotal = $133,240 )
2019	2019	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445, EDIFICIO 24, CC 30	SAN MARTIN	BUENOS AIRES	B1650KNA		ARG	Allergy and Infectious Diseases Research	000	6	4/1/2019	COMPETING CONTINUATION	$133,240
2019	2018	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445, EDIFICIO 24, CC 30	SAN MARTIN	BUENOS AIRES	B1650KNA		ARG	Allergy and Infectious Diseases Research	001	5	9/4/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $133,240

Issue Date FY: 2018 ( Subtotal = $135,000 )
2018	2018	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445, EDIFICIO 24, CC 30	SAN MARTIN	BUENOS AIRES	B1650KNA		ARG	Allergy and Infectious Diseases Research	000	5	3/22/2018	NON-COMPETING CONTINUATION	$135,000
														Subtotal = $135,000

Issue Date FY: 2017 ( Subtotal = $134,200 )
2017	2017	FUNDACION INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS	COLECTORA DE AVENIDA GENERAL PAZ 5445, EDIFICIO 24, CC 30	SAN MARTIN	BUENOS AIRES	B1650KNA		ARG	Allergy and Infectious Diseases Research	000	4	4/10/2017	NON-COMPETING CONTINUATION	$134,200
														Subtotal = $134,200

Issue Date FY: 2016 ( Subtotal = $134,040 )
2016	2016	INSTITUTE FOR RESEARCH IN BIOTECHNOLOGY FOUNDATION	Colectora de Avenida General Paz 54	San Martin				ARG	Allergy and Infectious Diseases Research	000	3	4/1/2016	NON-COMPETING CONTINUATION	$134,040
														Subtotal = $134,040

Issue Date FY: 2015 ( Subtotal = $133,240 )
2015	2015	INSTITUTE FOR RESEARCH IN BIOTECHNOLOGY FOUNDATION	Colectora de Avenida General Paz 54	San Martin				ARG	Allergy and Infectious Diseases Research	000	2	3/20/2015	NON-COMPETING CONTINUATION	$133,240
														Subtotal = $133,240

Issue Date FY: 2014 ( Subtotal = $133,440 )
2014	2014	INSTITUTE FOR RESEARCH IN BIOTECHNOLOGY FOUNDATION	Colectora de Avenida General Paz 54	San Martin				ARG	Allergy and Infectious Diseases Research	000	1	3/28/2014	NEW	$133,440
														Subtotal = $133,440

Grand Total All Awards = $1,340,760

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Role in pathogenesis and parasite cell biology of the trans-sialidase from Trypanosoma cruzi, the agent of Chagas Disease

Award Number: R01AI104531

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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