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P granules and control of germ cell development

Award Number: R01GM109053
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2014
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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P granules and control of germ cell development - Abstract Germ cells carry out the reproductive function of multicellular organisms, and normal germ cell development ensures survival of the species. Germ granules are conserved cytoplasmic organelles of germ cells, essential for survival, differentiation, and function of these cells. Mutations in germ granule components or loss of their expression lead to infertility in model organisms and are associated with infertility in humans. By contrast, inappropriate expression of germ granule components in somatic cells is linked to carcinogenesis in humans. Many RNA-binding proteins and developmentally regulated mRNAs are found enriched in germ granules, leading to a hypothesis that these organelles function in regulation of mRNA stability or translational activity; yet, the molecular function of these organelles is still undefined. The nematode C. elegans has been instrumental for analysis of mRNA translational control in germline development. Through focusing on cofactors that promote localization of RNA-binding regulatory protein FBF-2 to germ granules (called P granules in this species) in germline stem cells we have generated a set of innovative tools that will address key mechanisms through which P granules regulate FBF-2 activity. By integrating genetic, molecular, biochemical and imaging-based approaches, we will: 1) Determine how FBF-2 interaction with a cofactor protein DLC-1 important for P granule localization impacts translational repression exerted by FBF-2; 2) Define the mechanisms of P granule remodeling that specifically degrade FBF-2 at the onset of meiosis when stem cells transition from proliferation to differentiation; 3) Determine the role of DLC-1 binding to core P granule components in regulation of stability of embryonic P granules and in recruitment of transient P granule components such as FBF-2 to adult germline P granules. Our experimental system is poised to reveal specific molecular mechanisms mediating the interplay between germ granules and translational regulation. Since germ granules are conserved organelles and our research focuses on conserved regulatory proteins, studies in this model system will provide critical insight into the causes of infertility in humans.


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 = $0 )
2024	2022	UNIVERSITY OF MONTANA	32 CAMPUS DR	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	000	9	4/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $293,020 )
2022	2022	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	000	9	5/30/2022	NON-COMPETING CONTINUATION	$293,020
														Subtotal = $293,020

Issue Date FY: 2021 ( Subtotal = $293,221 )
2021	2021	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	000	8	5/17/2021	NON-COMPETING CONTINUATION	$293,221
														Subtotal = $293,221

Issue Date FY: 2020 ( Subtotal = $293,413 )
2020	2020	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	002	7	5/29/2020	NON-COMPETING CONTINUATION	$293,413
2020	2019	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	001	6	5/6/2020	COMPETING CONTINUATION	$1
2020	2018	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	000	5	5/6/2020	NON-COMPETING CONTINUATION	-$1
														Subtotal = $293,413

Issue Date FY: 2019 ( Subtotal = $311,149 )
2019	2019	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	001	6	8/30/2019	COMPETING CONTINUATION	$311,149
2019	2018	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	000	5	8/27/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $311,149

Issue Date FY: 2018 ( Subtotal = $272,498 )
2018	2018	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	000	5	2/19/2018	NON-COMPETING CONTINUATION	$245,248
2018	2018	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	001	5	5/31/2018	NON-COMPETING CONTINUATION	$27,250
														Subtotal = $272,498

Issue Date FY: 2017 ( Subtotal = $272,498 )
2017	2017	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	001	4	6/19/2017	NON-COMPETING CONTINUATION	$27,250
2017	2017	UNIVERSITY OF MONTANA	32 CAMPUS DR MAIN HALL	MISSOULA	MT	59812	MISSOULA	USA	Biomedical Research and Research Training	000	4	2/14/2017	NON-COMPETING CONTINUATION	$245,248
														Subtotal = $272,498

Issue Date FY: 2016 ( Subtotal = $270,446 )
2016	2016	UNIVERSITY OF MONTANA	**	MISSOULA	MT	59801	MISSOULA	USA	Biomedical Research and Research Training	000	3	2/1/2016	NON-COMPETING CONTINUATION	$270,446
														Subtotal = $270,446

Issue Date FY: 2015 ( Subtotal = $266,453 )
2015	2015	UNIVERSITY OF MONTANA	**	MISSOULA	MT	59801	MISSOULA	USA	Biomedical Research and Research Training	000	2	2/25/2015	NON-COMPETING CONTINUATION	$266,453
														Subtotal = $266,453

Issue Date FY: 2014 ( Subtotal = $260,338 )
2014	2014	UNIVERSITY OF MONTANA	**	MISSOULA	MT	59801	MISSOULA	USA	Biomedical Research and Research Training	000	1	2/27/2014	NEW	$260,338
														Subtotal = $260,338

Grand Total All Awards = $2,533,036

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P granules and control of germ cell development

Award Number: R01GM109053

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2014

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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