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Germ cell specification and differentiation in planarians

Award Number: R01HD043403
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/09/2003
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Germ cell specification and differentiation in planarians - Project Summary/Abstract Germ cells give rise to gametes–oocytes and sperm–that fuse to create a totipotent zygote, which divides and generates all the cells of an organism. During development, a new germ cell lineage must be established and differentiate properly to ensure propagation of the species. Most knowledge of germ cell specification and development comes from model organisms in which maternal determinants specify germ cells early in embryogenesis. By contrast, many animals (including mammals) specify their germ cells in response to inductive cues from surrounding cells later in development. Despite these differences in germline establishment, all germ cells share several important features, such as intrinsic transcriptional repression of somatic cell programs and dependence on extrinsic factors from somatic support cells. The free-living planarian flatworm, Schmidtea mediterranea, is well known for its extraordinary regenerative prowess, which relies on a population of pluripotent somatic stem cells. Planarians specify their germ cells post-embryonically from these somatic stem cells in response to inductive cues. Strikingly, planarians can even regenerate new germ cells de novo. Work over the past decade has established the planarian as a tractable model in which to study germ cell biology, and several intrinsic and extrinsic factors that regulate distinct aspects of male germline development–specification, maintenance, and differentiation–have been identified. However, almost nothing is known about female germ cell development in these animals, a critical gap because of the important role of egg production in the pathology of parasitic flatworm diseases. Here, building on extensive preliminary data from the applicant’s laboratory, the following two aims are proposed: (i) to functionally characterize the ovarian transcriptome; and (ii) to examine the role(s) of monoamine neurotransmitters in germ cell development. In Aim 1, laser capture microdissection and next-generation RNA sequencing will be used to create ovary- and testis-enriched transcriptomes. Validating ovary-enriched expression by in situ hybridization and characterizing gene function by RNA interference will enable the identification of germ cell-intrinsic and extrinsic regulators of female germ cell development. In Aim 2, cutting-edge mass spectrometry-based metabolomic studies will be combined with gene expression mapping and functional approaches to investigate the biogenic monoamines that signal locally and/or systemically to regulate germ cell development. The proposed experiments capitalize upon the planarian’s regenerative abilities and the functional genomic tools available for studying these animals to acquire a comprehensive view of the genes regulating female germ cell development. These studies are significant as they are expected to enhance understanding of germ cell biology across the metazoans and help guide future experiments on mammalian systems. In addition, this work will provide novel targets for disrupting reproduction in parasitic flatworms, which capitalize on their prolific reproductive output to propagate and afflict hundreds of millions of people worldwide.


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	THE MORGRIDGE INSTITUTE FOR RESEARCH, INC.	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	000	18	5/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $266,730 )
2022	2022	THE MORGRIDGE INSTITUTE FOR RESEARCH, INC.	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	000	18	5/16/2022	NON-COMPETING CONTINUATION	$266,730
														Subtotal = $266,730

Issue Date FY: 2021 ( Subtotal = $266,730 )
2021	2021	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	000	17	5/25/2021	NON-COMPETING CONTINUATION	$266,730
														Subtotal = $266,730

Issue Date FY: 2020 ( Subtotal = $272,174 )
2020	2020	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	000	16	5/21/2020	NON-COMPETING CONTINUATION	$272,174
														Subtotal = $272,174

Issue Date FY: 2019 ( Subtotal = $265,949 )
2019	2019	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	002	15	5/12/2019	NON-COMPETING CONTINUATION	$265,949
2019	2018	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	001	14	1/7/2019	COMPETING CONTINUATION	$60,554
2019	2016	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	000	13	1/7/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$60,554
														Subtotal = $265,949

Issue Date FY: 2018 ( Subtotal = $282,410 )
2018	2018	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	002	14	8/4/2018	COMPETING CONTINUATION	$282,410
2018	2016	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	001	13	8/3/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2018	2016	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	000	13	6/11/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $282,410

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	003	13	2/2/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$126,599
2017	2016	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Child Health and Human Development Extramural Research	001	13	1/27/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$246,604
2017	2016	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	002	12	2/2/2017	EXTENSION WITH OR WITHOUT FUNDS	-$126,599
2017	2016	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	12	1/27/2017	EXTENSION WITH OR WITHOUT FUNDS	-$246,604
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $246,604 )
2016	2016	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	12	5/3/2016	EXTENSION WITH OR WITHOUT FUNDS	$246,604
														Subtotal = $246,604

Issue Date FY: 2015 ( Subtotal = $242,867 )
2015	2015	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	11	5/15/2015	NON-COMPETING CONTINUATION	$242,867
														Subtotal = $242,867

Issue Date FY: 2014 ( Subtotal = $242,121 )
2014	2014	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	10	4/29/2014	NON-COMPETING CONTINUATION	$242,121
														Subtotal = $242,121

Issue Date FY: 2013 ( Subtotal = $236,391 )
2013	2013	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	9	6/7/2013	NON-COMPETING CONTINUATION	$236,391
														Subtotal = $236,391

Issue Date FY: 2012 ( Subtotal = $249,095 )
2012	2012	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	8	7/27/2012	COMPETING CONTINUATION	$249,095
														Subtotal = $249,095

Issue Date FY: 2010 ( Subtotal = $255,567 )
2010	2010	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Trans-NIH Recovery Act Research Support	000	7	7/21/2010	NON-COMPETING CONTINUATION	$255,567
														Subtotal = $255,567

Issue Date FY: 2009 ( Subtotal = $272,909 )
2009	2009	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Trans-NIH Recovery Act Research Support	002	6	7/14/2009	COMPETING CONTINUATION	$272,909
2009	2007	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	5	11/24/2008	NON-COMPETING CONTINUATION	$0
2009	2007	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	001	5	7/14/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $272,909

Issue Date FY: 2007 ( Subtotal = $254,280 )
2007	2007	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	5	12/8/2006	NON-COMPETING CONTINUATION	$254,280
														Subtotal = $254,280

Issue Date FY: 2006 ( Subtotal = $262,080 )
2006	2006	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	4	12/14/2005	NON-COMPETING CONTINUATION	$262,080
														Subtotal = $262,080

Issue Date FY: 2005 ( Subtotal = $268,591 )
2005	2005	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	3	12/22/2004	NON-COMPETING CONTINUATION	$268,591
														Subtotal = $268,591

Issue Date FY: 2004 ( Subtotal = $268,789 )
2004	2004	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	2	11/18/2003	NON-COMPETING CONTINUATION	$268,789
														Subtotal = $268,789

Issue Date FY: 2003 ( Subtotal = $268,982 )
2003	2003	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Child Health and Human Development Extramural Research	000	1		NEW	$268,982
														Subtotal = $268,982

Grand Total All Awards = $4,422,269

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Germ cell specification and differentiation in planarians

Award Number: R01HD043403

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/09/2003

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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