Friday, March 14, 2025 3/14/2025

Structure and Dynamics of the Telomerase Ribonucleoprotein

Award Number: R01GM095850
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The telomerase ribonucleoprotein (RNP) is required for maintaining telomeres, the specialized nucleoprotein structures that protect eukaryotic chromosome ends from aberrant processing and deleterious end-to-end fu- sion events. Telomerase catalyzes processive extension of telomere DNA via a unique catalytic mechanism that requires a strong functional interdependence of the telomerase RNA, telomerase reverse transcriptase (TERT), and several additional protein subunits. The primary objective of this proposal is to elucidate how conserved structural RNA and protein domains coordinate the processes of telomerase RNP assembly, cataly- sis, and recruitment to telomeres. To address this goal, we will utilize a multi-faceted experimental strategy that combines single-molecule biophysical techniques paired with computational, biochemical, and high-resolution structural approaches. We will study human telomerase and the enzyme from the model system Tetrahymena thermophila. In aim 1, we will employ biochemical structure probing, single-molecule Förster resonance energy transfer (smFRET), and x-ray crystallography to analyze structural intermediate states adopted by telomerase RNA and TERT during the RNP assembly pathway. In aim 2, we will use smFRET and a novel telomerase ac- tivity detection method to investigate conformational dynamics of protein and RNA domains that drive telomer- ase function. In aim 3, we will study the dynamic DNA handling properties of the telomerase enzyme. These experiments will focus on the molecular mechanisms for telomerase recruitment to telomeres as well as under- standing how the intrinsic folding properties of telomere DNA regulate telomerase catalysis.


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 = $0 )
2025	2023	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	13	1/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $356,895 )
2023	2023	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	13	11/8/2022	NON-COMPETING CONTINUATION	$321,206
2023	2023	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	13	2/14/2023	NON-COMPETING CONTINUATION	$35,689
														Subtotal = $356,895

Issue Date FY: 2022 ( Subtotal = $356,895 )
2022	2022	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	12	11/17/2021	NON-COMPETING CONTINUATION	$321,205
2022	2022	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	12	7/27/2022	NON-COMPETING CONTINUATION	$35,690
														Subtotal = $356,895

Issue Date FY: 2021 ( Subtotal = $356,895 )
2021	2021	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	11	12/2/2020	NON-COMPETING CONTINUATION	$321,205
2021	2021	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	11	2/17/2021	NON-COMPETING CONTINUATION	$35,690
														Subtotal = $356,895

Issue Date FY: 2020 ( Subtotal = $396,895 )
2020	2020	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	002	10	5/7/2020	COMPETING CONTINUATION	$89,374
2020	2020	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	10	11/29/2019	COMPETING CONTINUATION	$396,895
2020	2019	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	9	5/7/2020	NON-COMPETING CONTINUATION	-$89,374
														Subtotal = $396,895

Issue Date FY: 2019 ( Subtotal = $337,945 )
2019	2019	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	9	11/19/2018	NON-COMPETING CONTINUATION	$337,945
														Subtotal = $337,945

Issue Date FY: 2018 ( Subtotal = $337,945 )
2018	2018	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	8	5/24/2018	NON-COMPETING CONTINUATION	$33,795
2018	2018	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	8	11/9/2017	NON-COMPETING CONTINUATION	$304,150
														Subtotal = $337,945

Issue Date FY: 2017 ( Subtotal = $369,845 )
2017	2017	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	004	7	9/5/2017	SUPPLEMENT FOR EXPANSION	$31,900
2017	2017	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	003	7	8/15/2017	NON-COMPETING CONTINUATION	$33,795
2017	2017	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	002	7	11/21/2016	NON-COMPETING CONTINUATION	$304,150
2017	2016	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	6	11/3/2016	COMPETING CONTINUATION	$62
2017	2015	UNIVERSITY OF CALIFORNIA, SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	5	11/3/2016	NON-COMPETING CONTINUATION	-$62
														Subtotal = $369,845

Issue Date FY: 2016 ( Subtotal = $412,334 )
2016	2016	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	6	8/3/2016	SUPPLEMENT FOR EXPANSION	$75,000
2016	2016	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	6	11/20/2015	COMPETING CONTINUATION	$337,334
														Subtotal = $412,334

Issue Date FY: 2015 ( Subtotal = $287,810 )
2015	2015	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	5	11/25/2014	NON-COMPETING CONTINUATION	$259,029
2015	2015	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	5	1/15/2015	NON-COMPETING CONTINUATION	$28,781
														Subtotal = $287,810

Issue Date FY: 2014 ( Subtotal = $314,191 )
2014	2014	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	002	4	9/18/2014	SUPPLEMENT FOR EXPANSION	$25,000
2014	2014	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	4	11/21/2013	NON-COMPETING CONTINUATION	$260,272
2014	2014	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	4	3/11/2014	NON-COMPETING CONTINUATION	$28,919
														Subtotal = $314,191

Issue Date FY: 2013 ( Subtotal = $280,280 )
2013	2013	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	3	6/19/2013	NON-COMPETING CONTINUATION	$18,879
2013	2013	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	3	11/23/2012	NON-COMPETING CONTINUATION	$261,401
														Subtotal = $280,280

Issue Date FY: 2012 ( Subtotal = $291,588 )
2012	2012	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	2	11/25/2011	NON-COMPETING CONTINUATION	$262,429
2012	2012	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	001	2	4/10/2012	NON-COMPETING CONTINUATION	$29,159
														Subtotal = $291,588

Issue Date FY: 2011 ( Subtotal = $292,625 )
2011	2011	UNIVERSITY OF CALIFORNIA-SANTA CRUZ	1156 HIGH STREET	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Biomedical Research and Research Training	000	1	12/3/2010	NEW	$292,625
														Subtotal = $292,625

Grand Total All Awards = $4,392,143

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Structure and Dynamics of the Telomerase Ribonucleoprotein

Award Number: R01GM095850

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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