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Stress Responsive Reprogramming of Translating mRNA Pools in C. neoformans

Award Number: R01AI131977
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: 05/10/2017
PERIOD OF PERFORMANCE END DATE: 10/31/2023

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Stress Responsive Reprogramming of Translating mRNA Pools in C. neoformans - Abstract: Cryptococcus neoformans is a major comorbidity of HIV infection and transplantation with high mortality rates due to the toxicity and limited availability and efficacy of existing antifungal agents. As an environmental saprophyte, cryptococcal pathogenesis requires adaptation to the environment of the human host. Our work has led us to the scientific premise that stress adaptation in C. neoformans requires two sequential post- transcriptional events. First, the accelerated degradation mRNAs encoding metabolically expensive processes such as the translational machinery, and second, the translation of stress response mRNAs via cap- independent translation mechanisms on recycled ribosomes. This premise implicates the ribosome as a sensor of cellular stress through translation quality control mechanisms. The aims in this proposal will investigate co- translational quality control as a trigger for accelerated mRNA degradation in response to temperature sturess (Aim1) and will investigate cap-independent translation mechanisms (Aims 2) in stress adaptation. Aim 2 will focus on two CNBP orthologues expressed in C. neoformans that we hypothesize to regulate translation via internal ribosome entry sites (IRES) in response to temperature and oxidative stress. Finally, we will assess the contributing role of ribosome-associated quality control in starvation stress responsive translation and define the contributions of each quality control pathway in the response of C. neoformans to compound stressors (Aim 3). These studies will be the first investigation of translation in C. neoformans, and include the first application of ribosome profiling in this pathogen. Translation is known to be pharmacologically targetable but conservation in eukaryotes is thought to be a hindrance. Only through molecular investigation of translation regulation can fungal-specific aspects of the process be identified for future investigation as drug targets.


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 = $516,660 )
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	001	7	12/31/2024	SUPPLEMENT FOR EXPANSION	$66,758
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	7	12/30/2024	NON-COMPETING CONTINUATION	$449,902
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	003	6	1/21/2025	COMPETING CONTINUATION	$1,235
2025	2021	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	002	5	1/21/2025	NON-COMPETING CONTINUATION	-$1,235
														Subtotal = $516,660

Issue Date FY: 2024 ( Subtotal = $513,530 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	001	6	6/18/2024	SUPPLEMENT FOR EXPANSION	$41,694
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	6	2/6/2024	COMPETING CONTINUATION	$426,176
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	002	6	9/4/2024	COMPETING CONTINUATION	$45,660
														Subtotal = $513,530

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	5	4/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $457,683 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	5	4/13/2021	NON-COMPETING CONTINUATION	$457,683
														Subtotal = $457,683

Issue Date FY: 2020 ( Subtotal = $456,205 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	001	4	6/9/2020	SUPPLEMENT FOR EXPANSION	$64,095
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	4	4/13/2020	NON-COMPETING CONTINUATION	$392,110
														Subtotal = $456,205

Issue Date FY: 2019 ( Subtotal = $392,662 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	3	4/11/2019	NON-COMPETING CONTINUATION	$392,662
														Subtotal = $392,662

Issue Date FY: 2018 ( Subtotal = $393,162 )
2018	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	2	4/5/2018	NON-COMPETING CONTINUATION	$393,162
														Subtotal = $393,162

Issue Date FY: 2017 ( Subtotal = $387,215 )
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Allergy and Infectious Diseases Research	000	1	5/10/2017	NEW	$387,215
														Subtotal = $387,215

Grand Total All Awards = $3,117,117

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Stress Responsive Reprogramming of Translating mRNA Pools in C. neoformans

Award Number: R01AI131977

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: 05/10/2017

PERIOD OF PERFORMANCE END DATE: 10/31/2023

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