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Yeast Ribosome Biogenesis

Award Number: R01GM028301
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Yeast Ribosome Biogenesis - PROJECT SUMMARY/ABSTRACT Ribosomes are complex ribonucleoprotein particles that catalyze protein synthesis in almost all cells in nature. The long-term goal of this project is to understand how the 80 proteins and four rRNAs comprising eukaryotic ribosomes are assembled in vivo. We use the yeast Saccharomyces cerevisiae to facilitate molecular genetic approaches, and cultured Hela cells to enable us to visualize the nucleolus, the cellular compartment where ribosomes are made. Production of ribosomes is tightly linked to cell growth and proliferation. Consequently, dysregulation of ribosome biogenesis and nucleolar integrity is linked to many diseases such as cancer, neurodegenerative diseases, or developmental disorders. Because pathways of ribosome biogenesis are very conserved, our studies in yeast will help understand mechanisms of regulation and dysregulation of ribosome production in humans. Ribosome biogenesis requires a dynamic series of remodeling steps in which protein and RNA interactions are established and reconfigured. These steps are made more efficient and more accurate by the activities of more than 200 assembly factors present in nascent yeast ribosomes, which are required for their assembly, and conserved across eukaryotes. To enable in-depth studies of mechanisms driving ribosome assembly, we focus on one interval: just prior to, during, and immediately after exit of large ribosomal subunit precursors from the nucleolus into the nucleoplasm. During this stage, several domains of ribosomal RNA are rearranged, numerous assembly factors complete their functions and exit from pre-ribosomes, and new assembly factors enter the particles. We want to learn how these dynamic remodeling steps are powered forward by energy-consuming assembly factors present at this stage. We are also investigating interconnections between ribosome assembly and the nucleolus, the prominent biomolecular condensate thought to be formed through multivalent interactions between pre-ribosomes and other nucleolar components. However, it is not clear exactly how ribosome assembly creates a nucleolus, nor how material properties of the nucleolus enable efficient ribosome assembly. We propose experiments to address the following questions: (1) How do the RNA helicases/ATPases Drs1, Has1, Dbp10, and Spb4 power maturation of pre-60S subunits during mid to late nucleolar stages of assembly? (2) How does the structure and composition of pre- ribosomes enable them to be retained in the nucleolus? (3) How does ribosome assembly contribute to the morphology and fluidity of the nucleolus?


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 = $333,619 )
2025	2025	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	43	2/20/2025	NON-COMPETING CONTINUATION	$333,619
														Subtotal = $333,619

Issue Date FY: 2024 ( Subtotal = $398,911 )
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	42	2/14/2024	NON-COMPETING CONTINUATION	$322,920
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	42	8/27/2024	SUPPLEMENT FOR EXPANSION	$40,112
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	42	7/15/2024	NON-COMPETING CONTINUATION	$35,879
														Subtotal = $398,911

Issue Date FY: 2023 ( Subtotal = $404,592 )
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	41	5/17/2023	SUPPLEMENT FOR EXPANSION	$37,787
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	41	2/7/2023	NON-COMPETING CONTINUATION	$358,053
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	41	5/1/2023	SUPPLEMENT FOR EXPANSION	$8,752
														Subtotal = $404,592

Issue Date FY: 2022 ( Subtotal = $357,339 )
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	40	8/24/2022	COMPETING CONTINUATION	$970
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	40	4/6/2022	COMPETING CONTINUATION	$357,339
2022	2021	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	39	8/24/2022	NON-COMPETING CONTINUATION	-$970
														Subtotal = $357,339

Issue Date FY: 2021 ( Subtotal = $362,639 )
2021	2021	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	39	2/18/2021	NON-COMPETING CONTINUATION	$362,639
														Subtotal = $362,639

Issue Date FY: 2020 ( Subtotal = $362,621 )
2020	2020	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	38	2/24/2020	NON-COMPETING CONTINUATION	$362,621
														Subtotal = $362,621

Issue Date FY: 2019 ( Subtotal = $362,598 )
2019	2019	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	37	3/1/2019	NON-COMPETING CONTINUATION	$362,598
2019	2018	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	36	2/10/2019	COMPETING CONTINUATION	$65
2019	2017	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	35	2/10/2019	NON-COMPETING CONTINUATION	-$65
														Subtotal = $362,598

Issue Date FY: 2018 ( Subtotal = $362,570 )
2018	2018	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	36	4/2/2018	COMPETING CONTINUATION	$362,570
2018	2017	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	35	3/28/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $362,570

Issue Date FY: 2017 ( Subtotal = $335,663 )
2017	2017	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	35	2/16/2017	NON-COMPETING CONTINUATION	$302,096
2017	2017	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	35	6/20/2017	NON-COMPETING CONTINUATION	$33,567
														Subtotal = $335,663

Issue Date FY: 2016 ( Subtotal = $336,474 )
2016	2016	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	34	3/9/2016	NON-COMPETING CONTINUATION	$336,474
														Subtotal = $336,474

Issue Date FY: 2015 ( Subtotal = $337,253 )
2015	2015	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	33	2/13/2015	NON-COMPETING CONTINUATION	$337,253
														Subtotal = $337,253

Issue Date FY: 2014 ( Subtotal = $337,253 )
2014	2014	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	32	4/18/2014	COMPETING CONTINUATION	$337,253
2014	2013	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	31	4/15/2014	SUPPLEMENT FOR EXPANSION	$0
2014	2012	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	31	4/15/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $337,253

Issue Date FY: 2013 ( Subtotal = $110,762 )
2013	2013	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	31	7/17/2013	SUPPLEMENT FOR EXPANSION	$110,762
2013	2013	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	31	4/15/2014	SUPPLEMENT FOR EXPANSION	$0
2013	2012	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	31	7/17/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $110,762

Issue Date FY: 2012 ( Subtotal = $333,859 )
2012	2012	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	31	2/27/2012	NON-COMPETING CONTINUATION	$33,385
2012	2012	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	31	11/30/2011	NON-COMPETING CONTINUATION	$300,474
														Subtotal = $333,859

Issue Date FY: 2011 ( Subtotal = $334,780 )
2011	2011	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	30	12/1/2010	NON-COMPETING CONTINUATION	$304,345
2011	2011	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	30	6/7/2011	NON-COMPETING CONTINUATION	$30,435
														Subtotal = $334,780

Issue Date FY: 2010 ( Subtotal = $339,056 )
2010	2010	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	29	3/10/2010	NON-COMPETING CONTINUATION	$30,823
2010	2010	CARNEGIE-MELLON UNIVERSITY	5000 FORBES AVENUE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	29	11/25/2009	NON-COMPETING CONTINUATION	$308,233
														Subtotal = $339,056

Issue Date FY: 2009 ( Subtotal = $343,179 ) (Continued on the next page)
Grand Total All Awards = $8,625,178

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Yeast Ribosome Biogenesis

Award Number: R01GM028301

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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