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The identification of fundamental molecular regulators of ribosomal DNA and nucleolar organization in fission yeast

Award Number: F30GM140716
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Project Abstract Ribosome production relies on a nuclear organelle called the nucleolus. Within this structure, ribosomal DNA (rDNA) is transcribed to form RNA transcripts that associate with ribosomal proteins. Nucleolar architecture is altered in many human diseases including numerous cancers, prompting several studies to search for regulators of nucleolar morphology. While these studies rely on analysis of nucleolar proteins or ribosome production to identify molecular regulators, few studies have defined cell cycle-specific mechanisms for regulating nucleolar structure. Furthermore, no studies have examined the impact of rDNA spatial organization on nucleolar morphology despite rDNA loci’s known role as Nucleolar Organizer Regions. The long-term goal is to understand conserved regulatory mechanisms of rDNA and nucleolar organization. The overall objectives of this proposal are to (i) to identify molecular regulators of rDNA spatial organization and (ii) define the processes driving cell cycle-regulated nucleolar morphology. The central hypothesis is that the spatial organization of rDNA is regulated, in part, by chromosome organizing proteins and ribosome biogenesis; furthermore, these ribosome biogenesis processes are cell cycle-regulated, driving dynamic reorganization of nucleolar morphology during interphase. The rationale for this study is that identification of conserved molecular regulators of rDNA and nucleolar organization in fission yeast will provide a template for future research in higher organisms. This central hypothesis will be tested by two specific aims: 1) identify molecular regulators of rDNA spatial organization in fission yeast; and 2) define the processes driving cell cycle-regulated nucleolar morphology. For aim 1, a novel tool for analysis of rDNA spatial organization in live cells has been developed in fission yeast. This tool will be used to quantify rDNA spatial organization by fluorescence microscopy in candidate mutants with altered chromosome organization and DNA topology factors. This analysis will be expanded by a genome-wide high-throughput imaging screen to broadly identify regulators of rDNA spatial organization. Aim 2 will apply fluorescence microscopy, cell biology, and molecular biology approaches to examine the role of cell cycle-regulated ribosome biogenesis factors in interphase nucleolar morphology. These studies examine rDNA and nucleolar morphology in fission yeast, a model system notable for its application to higher organisms and ease of genetic manipulation. To understand the relationship between nucleolar morphology and human disease, the regulatory mechanisms behind rDNA and nucleolar organization must be identified. This study applies innovative imaging tools with advanced cellular and molecular biology techniques to broadly identify fundamental molecular regulators of rDNA and nucleolar morphology, providing a framework for future studies in human cells.


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: 2024 ( Subtotal = $55,194 )
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Biomedical Research and Research Training	001	4	1/5/2024	SUPPLEMENT FOR EXPANSION	$55,194
2024	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Biomedical Research and Research Training	000	4	1/4/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $55,194

Issue Date FY: 2023 ( Subtotal = $55,194 )
2023	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Biomedical Research and Research Training	003	4	7/27/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$38,735
2023	2023	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	002	3	7/26/2023	NON-COMPETING CONTINUATION	-$38,735
2023	2023	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	001	3	3/1/2023	NON-COMPETING CONTINUATION	$942
2023	2023	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	000	3	12/21/2022	NON-COMPETING CONTINUATION	$54,252
														Subtotal = $55,194

Issue Date FY: 2022 ( Subtotal = $36,913 )
2022	2022	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	001	2	4/8/2022	SUPPLEMENT FOR EXPANSION	$2,500
2022	2022	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	000	2	12/21/2021	NON-COMPETING CONTINUATION	$33,697
2022	2022	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH ST	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	002	2	6/8/2022	NON-COMPETING CONTINUATION	$716
														Subtotal = $36,913

Issue Date FY: 2021 ( Subtotal = $34,546 )
2021	2021	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	002	1	2/3/2021	NEW	$516
2021	2021	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	000	1	12/30/2020	NEW	$34,030
2021	2021	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 E 50TH	KANSAS CITY	MO	64110	JACKSON	USA	Biomedical Research and Research Training	001	1	12/30/2020	NEW	$0
														Subtotal = $34,546

Grand Total All Awards = $181,847

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The identification of fundamental molecular regulators of ribosomal DNA and nucleolar organization in fission yeast

Award Number: F30GM140716

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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