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The cell cycle of T. gondii bradyzoites within tissue cysts:in vivo development of an HIV-AIDS opportunistic parasite

Award Number: R21AI122894
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: 02/01/2016
PERIOD OF PERFORMANCE END DATE: 01/31/2019

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The cell cycle of T. gondii bradyzoites within tissue cysts:in vivo development of an HIV-AIDS opportunistic parasite - ¿ DESCRIPTION (provided by applicant): Toxoplasmic encephalitis (TE) is one of the HIV-AIDS defining opportunistic infections that is associated with the reactivation of the chronic form of te infection, mediated by bradyzoites, within tissue cysts in the CNS. Despite the central role in the pathogenesis of HIV-AIDS associated toxoplasmosis, little is known about the biology of tissue cysts and the bradyzoite stage of the parasite they contain. Among the key limitations in studying the progression of the chronic phase and the mechanisms by which latency is established, maintained and lost during reactivation has been that rigorous insights into the physiology and development of bradyzoites in vivo has not been possible. Toward removing this major limitation we have initiated a comprehensive research program to understand bradyzoite biology by the development of approaches that directly address bradyzoite replication within tissue cysts in the in vivo context. These initial studies reveal that bradyzoites possess a previously unappreciated capacity for replication and metabolism that can be exploited in the development drugs to target what has been a traditionally refractory state. With the present study we aim to establish not only a new paradigm for bradyzoite biology but also develop the experimental methodologies to dissect bradyzoite replication we have been able to conclusively detect occurs challenging the existing dogma that bradyzoites are largely dormant entities. Our initial studies provide a new window into the dynamics of bradyzoite growth within tissue cysts which exhibit a level of complexity and sophistication that has not been previously appreciated. In this exploratory and developmental study we focus on the generation of new experimental approaches to directly interrogate and dissect the progression of the cell cycle within bradyzoites. Such insights would fill a vast gap in our knowledge that has stymied the development of treatments that are targeted toward the elimination of tissue cysts and bradyzoites. Targeting of tissue cysts and bradyzoites would eliminate the primary trigger of toxoplasmic encephalitis in the HIV-AIDS.


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: 2019 ( Subtotal = -$7,728 )
2019	2017	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Microbiology and Infectious Diseases Research	000	2	5/23/2019	NON-COMPETING CONTINUATION	-$7,728
														Subtotal = -$7,728

Issue Date FY: 2017 ( Subtotal = $188,125 )
2017	2017	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Microbiology and Infectious Diseases Research	000	2	1/27/2017	NON-COMPETING CONTINUATION	$188,125
														Subtotal = $188,125

Issue Date FY: 2016 ( Subtotal = $225,750 )
2016	2016	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Microbiology and Infectious Diseases Research	000	1	1/20/2016	NEW	$225,750
														Subtotal = $225,750

Grand Total All Awards = $406,147

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The cell cycle of T. gondii bradyzoites within tissue cysts:in vivo development of an HIV-AIDS opportunistic parasite

Award Number: R21AI122894

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: 02/01/2016

PERIOD OF PERFORMANCE END DATE: 01/31/2019

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